Next Article in Journal
Osteogenic Differentiation Effect of Human Periodontal Ligament Stem-Cell Initial Cell Density on Autologous Cells and Human Bone Marrow Stromal Cells
Next Article in Special Issue
Δ8-THC Induces Up-Regulation of Glutamatergic Pathway Genes in Differentiated SH-SY5Y: A Transcriptomic Study
Previous Article in Journal
Design, Synthesis and Biological Evaluation of Multi-Target Anti-Cancer Agent PYR26
Previous Article in Special Issue
A Postsynaptic Density Immediate Early Gene-Based Connectome Analysis of Acute NMDAR Blockade and Reversal Effect of Antipsychotic Administration
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Advances in the Electrophysiological Recordings of Long-Term Potentiation

1
Department of Neuroscience, City University of Hong Kong, Kowloon, Hong Kong
2
Research Institute of City University of Hong Kong, Shenzhen 518057, China
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(8), 7134; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24087134
Submission received: 13 February 2023 / Revised: 1 April 2023 / Accepted: 6 April 2023 / Published: 12 April 2023
(This article belongs to the Special Issue New Insights into Synapse Structure and Function)

Abstract

:
Understanding neuronal firing patterns and long-term potentiation (LTP) induction in studying learning, memory, and neurological diseases is critical. However, recently, despite the rapid advancement in neuroscience, we are still constrained by the experimental design, detection tools for exploring the mechanisms and pathways involved in LTP induction, and detection ability of neuronal action potentiation signals. This review will reiterate LTP-related electrophysiological recordings in the mammalian brain for nearly 50 years and explain how excitatory and inhibitory neural LTP results have been detected and described by field- and single-cell potentials, respectively. Furthermore, we focus on describing the classic model of LTP of inhibition and discuss the inhibitory neuron activity when excitatory neurons are activated to induce LTP. Finally, we propose recording excitatory and inhibitory neurons under the same experimental conditions by combining various electrophysiological technologies and novel design suggestions for future research. We discussed different types of synaptic plasticity, and the potential of astrocytes to induce LTP also deserves to be explored in the future.

1. Introduction

Neuronal cells and glial cells are the main components of the brain. Approximately 50% of the brain is neuronal cells; the other half is glial cells, which all play an important role in the mammalian brain [1,2,3,4]. Billions of neurons are connected and communicate via synapses inextricably linked to behavior, memory, and neurological diseases. Synaptic plasticity is a change in neural connection strength that occurs in response to activity [5]. Reorganization of the structural and functional connections of synapses occurs in response to internal or external stimuli, leading to the strengthening or weakening of synaptic connections via synaptic plasticity [6,7]. Long-term potentiation (LTP) has been widely used as an ideal model for studying synaptic plasticity, learning, and memory [7,8,9].
LTP is a classical synaptic plasticity caused by the persistent stimulation-induced enhancement of neuronal signaling. Specifically, when neurons receive this series of stimulations, subsequent single-pulse stimulations cause an enhanced and prolonged excitatory postsynaptic potential (EPSP) or inhibitory postsynaptic current (IPSC) in the postsynaptic population potential [10]. A brief stimulation can induce LTP for periods ranging from a few minutes to several months, and this persistent state of LTP differentiates it from other forms of synaptic plasticity [11]. Although different brain regions exhibit different forms of LTP and different mediators can modulate LTP, the signature of LTP activity data does not change (as shown in Figure 1D,E). LTP is triggered by postsynaptic depolarization of the cell membrane and elevated calcium concentration.
In vivo extracellular recordings [12], microelectrode arrays [13], and patch clamps [14] are the most common electrophysiological techniques used to detect LTP [6,7,8]. As a result, the data utilized to assess LTP formation may also be divided into the field and individual potentials. Field potentials were identified using in vivo extracellular recordings and microelectrode arrays, whereas individual potentials were detected using the patch clamp. The first recording of LTP activity in neuronal cells was conducted using microelectrode arrays in the hippocampus (HP) of mice [15]. However, in recording the acute plasticity induction protocol of excitatory or inhibitory synapses, they only recorded a single type of neuron action potentiation with LTP (Table 1). As mentioned above, the recordings of detection or comparison of the firing states of these two types of neurons (excitatory and inhibitory) were limited at the same time and space.
Here, we raise the following three questions:
  • Why did most researchers use field potential to detect LTP at excitatory synapses while using the single-cell potential to detect LTP at inhibitory synapses, respectively?
  • What is the mechanism of LTP at the inhibitory synapses? Is this similar to excitatory synapses?
  • Do LTP and LTP of inhibition (iLTP) occur independently? What does an inhibitory neuron do while excitatory neurons are stimulated to induce LTP?
Table 1. The timeline and recordings of long-term potentiation studies.
Table 1. The timeline and recordings of long-term potentiation studies.
YearMechanism or EventInduction Recording MethodBrain Area Ref.
1970–1980Discovery of LTP10–20 Hz
100 Hz
Extracellular micro-electrodes
Population EPSP
HP, CA1, CA3 [10]
Brain slice recording on LTP3–50 HzPopulation EPSPHP, CA1[16]
LTP needs synaptic transmission100 HzPopulation EPSPHP[17]
Ca2+- dependent100 HzExtracellular population spike
EPSP
HP, CA1[18]
1980–1990NMDAR
Postsynaptic Ca2+
>35 Hz Extracellular recording HP, CA1[19,20,21,22]
Activation of NMDA receptors blocks GABAergic inhibitionTetanic electrical stimuliExtra and intracellular recording
IPSP
HP, CA1[23]
LTP needs NMDARHFSIntracellular recordingVisual cortex[24]
1990–2000Single-cell recording EPSP-spikeHFSIntracellular recordingCA1[25]
GABABR regulates NMDA to induce LTP0.5–100 HzMonosynaptic inhibitory pathway
IPSC
HP, granule cells[26,27]
Induction of LTP needs mGluRsHFS
100 Hz
Extracellular field potentials
Whole-cell patch clamp
HP, CAl CA3[28,29]
NMDAR dependent
Ca2+
100 HzField potentials
EPSP
HP[30]
NO mediate LTP100 HzField potentials
EPSP
HP[31]
GABA AR
Independent
HFS 50 HzIntracellular recording
IPSP
visual cortex (LV)[32]
GABABR dependent
Ca2+ Release
HFS 50 HzIntracellular and
whole-cell recording
IPSP/IPSC
visual cortex (LV)[33]
NMDA-dependent inhibition100 HzWhole-cell and extracellular recording HP, CA1[34]
Bi-directional plasticity100 HzIntracellular recordingHP[35]
NO mediate LTP50 HzWhole-cell ruptured patch recording
EPSCs
HP[36]
GABAergic synaptic LTP0.1 HzIntracellular recordingNeonatal rats, HP[37]
2000–2010mGluR
GABA B R
Postsynaptic Ca2+
TBSWhole-cell recording
IPSP
HP
CA1
[38]
NMDAR-nondependentHFS (30 Hz)Whole-cell recording
IPSP and EPSP
Lateral Amygdala[39]
The pairing of presynaptic activity with sub-threshold
postsynaptic depolarization
Postsynaptic
50 Hz
postsynaptic depolarization-60 mV
Patch clamp
IPSC
Visual Cortex(LIV)[40]
GABA AR
NO initiates iLTP
NMDA-independent
HFSWhole-cell patch clamp
IPSC
VTA[41]
BDNF-TrkBHFS (50 Hz)Whole-cell patch clamp
Voltage clamp
IPSC
Visual cortex (LV)[42,43]
mGluR5 postsynaptic calcium, NMDAR- nondependentTBSWhole-cell patch clamp
EPSP
The visual cortex, L II/III[44]
BDNF and cAMP-dependent PKALFS (0.05 Hz)Patch clamp–Voltage clamp
IPSP and IPSC
HP, CA3[45]
Astrocyte-induced independent-LTP 0.5 HzWhole-cell patch clampHP, CA1, CA3[46]
D-serine from astrocytes activates NMDAR100 HzWhole-cell recordingsHP[47,48]
2010–2020BDNF-TrkB 50 HzWhole-cell patch clamp
IPSC
Auditory Cortex (AC)[49]
Cholecystokinin (CCK) modulates the plasticity of GABA SynapsesHFSWhole-cell recording
IPSC
Dorsomedial Hypothalamus[50]
NMDAR triggers CCK releaseHFS (100 Hz)In vivo, fEPSPAC[51]
Dual-channel optogenetic LTP-inductionOptogenetic HFS (oHFS)
50 Hz
Field potential recording
fEPSP
Whole-cell recording
NMDAR/AMPA-EPSP
Dorsal striatum[52]
Astrocytic ATP is necessary for LTPCCKHFS (100 Hz)Whole-cell recordingHypothalamus[50]
Small increase in Astrocytic ATP releaseHFS (100 Hz)Extracellular field recordings, fEPSPHP, CA1[53]
2020–2023CCK Potentiates GABAergic Synapses20 HzWhole-cell patch clampVTA[54]
Spatial regulation of excitatory and inhibitory synaptic plasticityLFS
2 Hz, 4 Hz
Whole-cell patch clampHP[55]
Astrocyte dystrophy parallels impaired LTPHFS
100 Hz
Patch clampHP, CA1[56]
Optogenetic induction of orbitostriatal LTPoHFS
50 Hz
Whole-cell recording
oEPSCs
Dorsomedial Striatum[57]
Novel CCKR: GPR173 Mediates iLTPHFLSIn vivo extracellular and in vitro patch clamp Neocortex[58]
Capacitive energy storage in the phospholipid bilayerLFS
0.01 Hz
Patch clampDPhPC multilamellar vesicles (MLVs)[59]
Several studies have focused on different aspects of LTP, the interplay of molecular mechanisms, the effect of different stimulation protocols (such as intensity and frequency), and the spike timing of LTP involved in its formation. Here, we focus on the most fundamental but rarely discussed analysis of the experimental electrophysiological data of LTP detection. In this review, we summarize the experimental electrophysiological data of LTP and iLTP in mammalian brains over the past 50 years in an attempt to answer the above three questions.

2. Field Potential and Single-Cell Potential Recording in LTP

We summarized the different recording methods used to detect LTP at excitatory and inhibitory synapses to answer the first question. Based on this research, we further attempted to analyze why only single-cell potential recording was applied to detect LTP at inhibitory synapses but not field potential recording.

2.1. Field Potential Recording at Excitatory Synapses

Since 1966, when LTP was first discovered by Lømo and was reported in the HP of rabbits by Lømo and Bliss et al. in 1973, an electrophysiological system capable of monitoring population EPSPs was used [10,15,60]. This system enhances synaptic strengths in specific brain regions. The electrophysiological system resulted in a 43% increase in the amplitude of the EPSP population, which represents the depolarization of granule cells. Population spike amplitude reduction signaling is the most common sign of potentiation. The 40% amplitude of the population spike represents cell firing. LTP occurs if one or two of the conditions mentioned above are satisfied. The earliest LTP model above lays the foundation for the subsequent study and modeling of synaptic plasticity. The potential mechanism of excitatory synaptic LTP was studied by detecting the field potential.
The studies of LTP in the past 50 years are shown in Table 1, which shows that most LTP studies have recorded population excitatory neuronal potentials, especially in the HP. These studies focused on exploring various LTP mechanisms, including NMDAR-dependent LTP [61], NMDAR-nondependent LTP [62], voltage-dependent Ca2+ channels [63], and NMDAR triggering CCK release to induce LTP [51], as evidenced by field potential result data. Lømo discovered LTP using this population cell recording, a simple and convenient system to capture excitatory neuronal firing activity. This experimental device for measuring field potentials in vivo (in vivo recording, Figure 1A) and brain slices (MED64 multi-electrode array technology, Figure 1B) illustrates that the population EPSP reflects the overall excitability of the neuronal population [1,51,64]. Some studies also recorded LTP at specific excitatory synapses using whole-cell patch clamps but not field potential recording [65,66,67]. Compared to field potential recording, the patch clamp can precisely record specific neuronal firing patterns [67,68]. In contrast, the field potential recording technique was used for recording excitatory neuronal LTP in certain brain areas. One of the reasons is researchers used a patch clamp to record inhibitory neuronal activity, which will be discussed in the following chapter.
The penetrating microelectrode mainly used in the research is the microwire type. This type of microelectrode is implanted in the brain to record neural activity action potentials (APs) and local field potentials (LFPs). The method can provide more information than non-penetrating microelectrodes. It has been used short-term and documented in rodent studies with low levels of tissue damage [69]. The most obvious advantage of in vivo extracellular recording is that it cannot only simultaneously record the electrical activity of many neurons in multiple brain regions but also allow the use of population enhancement data to detect the excitatory synaptic action of the population when the animal is in a more natural state. In vivo extracellular recording allows the study of the brain by stimulating and exploring the temporal and spatial connections between neuronal firing in different brain regions by analyzing the firing patterns of neurons, thus understanding the brain’s coding mechanisms in various tasks. Additionally, using MED64 Multi-electrode Array Technology for brain slice studies is more convenient than in vivo and patch-clamp techniques. The alignment allows for the precise geometric assignment of stimulus and recording locations.
However, owing to the non-uniform distribution of voltage-dependent channels in dendrites [2], the EPSP and IPSP signals cancel each other out during recording, which indicates that the EPSP results in the field potential recordings are the sum of the EPSP and IPSP after computational processing by the recording system, which are not unitary data. Therefore, the field potentials can only reflect the sum of local neuronal activity but cannot show single-cell firing when the population activity is triggered, much less the excitatory or inhibitory state of neurons simultaneously. Therefore, it is difficult for researchers to detect the firing states of excitatory and inhibitory neurons under the same experimental conditions.
Although excitatory synaptic LTP has been one of the most studied forms of neuroplasticity thus far and field potentials are convenient to reflect its activity, the limitations of single-field potential recordings have led to many questions that cannot be adequately answered, hence the many controversial theories of LTP. Recently, combining two-photon microscopy and fluorescent labeling techniques with electrophysiological experiments has provided evidence of presynaptic enhancement during LTP [63]. The combination of intracellular or whole-cell recordings elucidated NMDAR-dependent LTP dependent on increased postsynaptic Ca2+ concentrations [33,70,71,72], as well as presynaptic voltage-dependent Ca2+ channels [73], with pharmacological findings of multiple forms of LTP, such as mGluR-dependence [72].
Furthermore, early experimental techniques’ limitations disregarded the inhibitory synapses’ long-term plasticity. When researchers use the field potential detection technique to detect and analyze LTP in excitatory neurons, the question arises: what about inhibitory synapses? The answer to this question can be found in the single-cell potentiation recordings of γ-aminobutyric acid (GABA)ergic inhibitory synapses.

2.2. Extracellular Ionic Currents That Are of Dual Nature

Changes in extracellular ion concentration are produced within the central nervous system as part of normal neuronal activity, which can affect neuronal activity by altering cellular resting potentials [74]. Many studies focused on the brain’s extracellular potassium concentration ([K+]0) partially regulated by K+ spatial buffering by glial cells. Newman et al. detected the efflux of K+ from dissociated salamander Müller cells using ion-selective microelectrodes, a kind of field potential recording, in 1984 [74], and, in isolated frog retina, after treatment with aspartate, the photoinduced change in the extracellular potassium ions concentration [K+]0 was similar to slow PIII potential (sPIII), both increased in the whole range of light stimulus durations [75]. (Relationship between photoinduced changes in the intercellular concentration of potassium ions and transretinal potential generation by the Muller cells of the retina) Newman and Odette established a model simulating retinal processes based on the K+ hypothesis, producing the b-wave response [76]. According to this model, a realistic sPIII potential responding to [K+]0 decreases in the distal retina, and the K+ reproduces accurately [76]. Additionally, increasing in [K+]0 in vitreous humor was detected by double-barreled K+-selective microelectrodes, recorded from frog and mudpuppy eyecups after light-evoked potassium increasing within the retina [77].
Astrocytes are gradually regarded as excellent targeted therapeutic candidates for treating neurological diseases. Measuring astrocyte activity in the brain is rather important for neurologic development. Astrocyte activity has been detected in the low-frequency band < 1 Hz, while the standard models of recordings of extracellular potentials can only capture higher frequency potential [78]. Normally, researchers detect extracellular potentials by combining multicompartmental models showing neural electrodynamics and volume conductor theory, limited to simulating the slow components of extracellular potentials, which depend on ion concentration and the effect on extracellular diffusion potentials glial buffering currents [79]. To solve the problem, Marte et al. established an electrodiffusive neuron-extracellular-glia (edNEG) model, considered the first model combining compartmental neuron modeling with an electrodiffusive framework for intra- and extracellular ion concentration dynamics in a local piece of neuro-glial brain tissue [79]. In another study, the extracellular electrical activity of human astrocytes was successfully recorded by separating the signals received from human astrocytes cultured on a microelectrode array (MEA) into seven frequency bands [78].

2.3. Single-Cell Potential Recording at Inhibitory Synapses

2.3.1. Intracellular Recordings

Artola and Singer used intracellular recordings to demonstrate that the activation threshold of the NMDA machinery, and, consequently, the susceptibility to LTP, was strongly influenced by inhibitory processes [24]. Activity-dependent plasticity of GABAergic synaptic transmission was studied in neonatal rat HP slices using intracellular recording techniques and illustrated that, during early development, bidirectional synaptic plasticity is expressed by GABAA receptors and that activation (or inactivation) of NMDA receptors determines LTP-GABAA induction [35].

2.3.2. Patch Clamp: Whole-Cell Recording

In the 1970s, patch-clamp techniques were introduced to the field of neuroscience to illustrate synaptic transmission and were then applied to LTP studies in 1987 [41,80,81,82]. Subsequently, in 1991, a combination of receptor antagonists and single-cell potential recording techniques demonstrated that GABAB receptors could modulate NMDA release to regulate LTP [26,27], which gradually highlighted GABAR and GABAergic neurons.
As shown in Table 1, the study of iLTP in inhibitory neurons has been much slower than the rapid development of early excitatory neuronal LTP studies. iLTP is attributed to the increased diversity of relatively sparse GABAergic interneurons, in addition to the limitations of the previously used simple and convenient field potential recording method mentioned above [83,84,85], which fails to exhibit the same consistent reflective state to plasticity induction as tightly packed pyramidal neurons in randomly sampled extracellular field potential recordings [86]. The above recordings would lead to difficulty in inducing and detecting LTP in GABAergic cells. The advent of single-cell recordings has allowed for a more comprehensive study of inhibitory neurons. It has greatly improved our understanding of inhibitory cells owing to advances in experimental equipment and the diversity of methods.
Presently, the study of inhibitory neurons mainly relies on patch clamps because of the characteristics of GABAergic interneurons and the diversity of recording modes in the patch clamp. Patch-clamp systems include current and voltage clamps, allowing researchers to quickly change the stimulus and recording modes. Moreover, the unique patch-clamp whole-cell recording technique solves the problem of an extremely negative signal-to-noise ratio compared with traditional intracellular recording, which makes compensation very easy. Thus, the patch-clamp technique enables the separation of synaptic structures from the effects of mixed networks and allows studying brain slices under controlled environmental conditions. For example, it can stimulate specific pathways independently and record specific postsynaptic cells without polluting synaptic input from other connected brain regions [87]. In addition, information obtained from whole-cell recordings (especially brain slices or in vivo recordings) reflects changes in cellular function (and even intercellular messaging) coupled with the ease of changing the extracellular fluid environment. Therefore, whole-cell recordings are more suitable for pharmacological studies of ion channels.

3. LTP Mechanisms of Excitatory and Inhibitory Synapses

Consistent increases in neurotransmitter release result in omnipresent forms of LTP [88]. Plenty of evidence suggests that neuronal activity can trigger sustained increases in neurotransmitter release at excitatory and inhibitory synapses, leading to LTP. The use of intracellular and patch-clamp recordings revealed various interesting mechanisms that trigger inhibitory synaptic LTP in different brain areas, indicating that iLTP may be associated with various phenomena. The expression of iLTP is induced by the release of the neurotransmitter GABA, which is exhibited by inhibitory synapses throughout the central nervous system (CNS) and can dynamically control information flow in neural circuits [89]. Understanding various mechanisms that induce GABA release is beneficial for understanding the balance between GABA excitation and inhibition.
Therefore, another important question we need to notice is the mechanism of LTP at inhibitory synapses (Figure 2) and the similarity at excitatory synapses. We have elucidated the similar mechanisms that produce LTP at inhibitory and excitatory synapses.

3.1. Nitric Oxide (NO)

NO is a kind of endothelium-derived relaxing factor [90], which is synthesized by NO synthase (calcium/calmodulin-dependent) with L-arginine as substrate [91]. Ca2+/calmodulin regulates constitutive expression types of the NOS family [92], confirming a possible connection to LTP and iLTP induction. Meanwhile, behavioral studies show that the NO/cGMP plays a role in learning and memory [93,94] because NO donors, l-Arginine, or cGMP analogs enhanced memory, whereas NOS inhibitors or genetic deletion hampered various types of memory [93].
It has been reported that, as one of the retrograde signals to maintain iLTP in GABAergic synapses in the VTA, NO first requires glutamate to activate the NMDA receptor, which increases postsynaptic calcium concentration. As a result, NO is released as a retrograde signal by NO synthase and also initiates sustained enhancement to increase cGMP levels to boost GABA release, which puts brain slices into use with NO scavengers (Mu-opioid receptors) to inhibit NO production. Single exposures to cocaine and nicotine and acute stress blocked NO-iLTP [41,95]. A combination of HFS and whole-cell recordings induced and recorded iLTP. iLTP is associated with modifying the coefficient of variation and the paired-pulse ratio of induced GABAA receptors. Furthermore, IPSCs are suggested to be maintained by a sustained increase in GABA release [41].
Similarly, in a series of hippocampal neuron (CA1 and CA3) experiments [96,97,98], it was proved that NO could activate soluble guanylate cyclase (sGC), which can catalyze the conversion of GTP into cGMP after activation, increasing the level of cGMP, thereby activating cGMP-dependent protein kinase (PKG) [99]. Following that, various proteases and phosphodiesterases exert their effects to increase the release of transmitters [100,101].
As required, NO is synthesized in the cell and dendrites rather than stored in synaptic vesicles, making NO-mediated transmission different from classical forms of neurotransmission. The biological properties of NO as a gaseous molecule allow it to freely permeate biomembranes and diffuse rapidly to control synaptic transmission and plasticity.

3.2. BDNF-TrkB

Brain-derived neurotrophic factor (BDNF) is a protein that promotes nerve growth activity, can regulate excitatory and inhibitory transmission [88], and significantly influences the development of CNS neurons. Part of the BNDF receptors belongs to the tyrosine-related receptor kinase family (Trk), among which TrkB has the highest affinity with BDNF and is the primary functional receptor of BDNF [102]. This neurotrophin regulates synaptic function in the hippocampus by modulating presynaptic transmitter release or enhancing postsynaptic transmitter sensitivity [103]. BDNF signaling plays a role in the pathogenesis of several important diseases, including Alzheimer’s disease (AD) [104], depression, schizophrenia, and anxiety disorders [103]. Modulation of BDNF pathways could, therefore, offer a feasible strategy to treat various neurological disorders.
Gubelini et al. combined pharmacology and whole-cell recording to prove that retrograde BDNF can enhance the inhibitory function [105], whereas TrkB conductivity inhibitors do not block the inhibitory function. Induction of iLTP requires elevated postsynaptic calcium, and intracellular calcium promotes BNDF release/secretion [106]. However, different evidence indicated whether BDNF is required for LTP by combining two-photon imaging: the types of LTP at Schaffer collateral synapses selectively required BDNF. According to these findings, different presynaptic and postsynaptic modules exhibit long-term plasticity [107]. The activation of presynaptic plasticity modules, but not postsynaptic modules, depends on BDNF release from CA3 neurons. Presynaptic neurons provide BDNF, and this type of LTP requires L-type voltage-gated Ca2+ channel activation [107]. There is also evidence that hippocampus volume has an association with BDNF-TrkB signaling [108,109].

3.3. NMDAR-Dependent

NMDAR is an ion channel receptor with high calcium permeability, which can regulate neuronal activity through different neurotransmitters [110]. The key mechanism by which NMDARs participate in postsynaptic LTP induction is voltage dependence. In order to activate postsynaptic NMDARs, two conditions need to occur simultaneously. First, glutamate needs to be released and bound with the help of postsynaptic NMDARs; second, the postsynaptic membrane needs to be depolarized to remove the block of extracellular Mg2+. Thus, calcium influx enters the postsynaptic cell from the extracellular space through the open NMDARs, which then activates a series of signaling molecules in the postsynaptic cell, including calmodulin (CaM), protein kinase A (PKA), cyclic AMP (cAMP), immediate early genes, and enzymes that produce diffusible retrograde messengers [111]. iLTP is also present in GABAergic stellate cells (SC inhibitory synapses), and, as with LTP in excitatory synapses, it requires GABAergic terminals to activate NMDAR [112,113,114]. Stimulation with glutamatergic inputs (parallel fibers) with similar physiological activity patterns triggered a sustained increase in GABA release from stellate cells using whole-cell recordings. Moreover, in combination with extracellular recordings, enhanced inhibitory transmission reduced the firing frequency and altered the pattern of action potential activity in stellate cells. Induction of sustained increases in GABA release requires activation of NMDA receptors, and pharmacological and genetic approaches have identified presynaptic cAMP/protein kinase A (PKA) signaling and the active zone protein RIM1α as key pathways required for sustained enhancement of GABA release. Thus, a common mechanism underlies the presynaptic plasticity of excitatory and inhibitory transmissions.
Inhibitory synaptic plasticity, triggered by short- and high-frequency inhibition of the postsynaptic electrical activity of GABAergic transmission, is essentially due to an increase in postsynaptic intracellular calcium [115]. Intracellular calcium can be altered postsynaptically by various mechanisms (e.g., PKC, CaMKII, Src, and PKA [87]). These protein kinases have dual roles in LTP formation and maintenance. On the one hand, calcium ions can immediately activate them and contribute to LTP induction. On the other hand, they have an autophosphorylation function. However, the modular process for long-term potentiation induction is extremely complex and has not been completely understood yet. Future experiments using whole-cell recordings in combination with pharmacology and genetics will provide a more thorough understanding soon.
Excitatory synapses produced homosynaptic and heterosynaptic LTP. Contrarily, iLTP mechanisms are heterosynaptic in nature, which can be induced by episodes of strong postsynaptic activity during which synapses are inactive, thereby directing any synapses that are irrelevant to heterosynaptic changes [116], and have the final goal of stimulating GABA to release into the GABAAR, which allows inhibitory interneurons to counteract prominent excitation and restrict neuronal activity transmission to control the output of the target neuron. It is worth mentioning that, since no synaptic stimulation is involved in the induction process due to the intracellular photolytic release of caged calcium ions and tonicity, LTP can be regarded as heterosynaptic.
In addition, as membrane clamp recordings are programmed to record synaptic functions, studying slices from inhibitory neurons or immature animals is becoming more common.

3.4. Glial Cells

Connecting neurons and glial cells are essential for neuroplasticity [117]. Growing evidence suggests that astrocytes are crucial for excitatory and inhibiting signaling [118]. Furthermore, gliotransmitters released by astrocytes, including ATP [117,119], D-serine [47,48], and adenosine [120], are necessary for NMDA-dependent LTP.
Importantly, glia, particularly astrocytes, bidirectionally communicate dynamically with neurons following information processing, neuronal activity, and behavior [121]. Briefly, astrocytes respond to neuronal activity and neurotransmitters by activating metabotropic receptors and releasing the gliotransmitters, which feed back to neurons [122,123]. The ATP released by astrocytes modulates synaptic transmission directly or through its metabolic product adenosine and can activate neuronal P2 receptors, P2X, and P2Y, which regulate synaptic homeostasis and plasticity [119,122]. In 2018, Adamsky et al. showed that activating astrocytic in CA1 induced LTP formation [124]. Furthermore, Stevens et al. demonstrated earliest that glial cells regulate neuronal activity by secreting D-serine [125]. Later, D-serine released from astrocytes, Ca2+-dependent, has been reported as closely related to LTP formation through modulating NMDA receptor function [47]. This study found that LTP formation could be blocked by clamping internal Ca2+ in individual CA1 astrocytes, and the blockade could be reversed by exogenous D-serine application [47]. Astrocyte–neuron communication was also related to synergism between vesicular and non-vesicular gliotransmission. Cortical astrocytes can release gliotransmitters, glutamate, and D-serine by combining SNARE-dependent exocytosis and non-vesicular mechanisms dependent on TREK-1 and Best1 channels, strongly affecting the glia-driven regulation of synaptic plasticity in hippocampus and neocortex [126]. Astrocytes have numerous large pore links. Molecular communication can travel a long distance. Neurons are divided from each other by the aquatic cleft of synapses and thus cannot interact directly with each other except through chemical communication [127]. However, astrocytes communicate extensively via large pores known as gap junctions, which may propagate molecular signaling to a long distance [128]. Moreover, this communication is enforced by polyamine spermine [127,128]. Polyamines, such as putrescine and spermine, are also gliotransmitters [118].
Putrescine and produced from putrescine GABA: some evidence pointing to an interesting mechanism. A type of gliotransmitters almost entirely stored in astrocytes: polyamines that can be released through various mechanisms. Polyamine putrescine (PUT) is an important source of astrocyte GABA production. Significant GABA release suggests that the astrocyte Glu-GABA exchange mechanism plays a key role in limiting ictal discharge [129]. In addition, polyamine spermine (SPM) is also accumulated in astrocytes but not neurons [118]. It can also modulate neuronal NMDA, AMPA, and kainate receptors [118]. This evidence may show a new mechanism for regulating iLTP.

4. Coordinated Plasticity of Excitatory and Inhibitory Synapses

Research on populations of glutamatergic and GABAergic synapses has previously addressed the coordinated plasticity of excitatory and inhibitory synapses. GABAergic synapses are similar to glutamatergic synapses, which can exhibit a variety of long-term plasticities at the pre- and postsynaptic levels [114,130,131].
Ravasenga et al. used double uncaging electrophysiology combined with single-particle tracking and pharmacology to demonstrate that induction of long-term potentiation at a single glutamatergic spine leads to inhibition of nearby GABAergic inhibitory synapses (within 3 μm, iLTD, as shown in Figure 3), while more distant synapses are enhanced (iLTP) and that such GABA_iLTP is heterosynaptic. Notably, this plastic change requires L-type calcium channels and calpain and is associated with decreased gephyrin aggregation and increased GABAAR mobility. Furthermore, this functional interaction is restricted to the dendritic microregions [55,132]. However, owing to the great diversity of GABAergic synaptic proteins [133] and the heterogeneity of GABAergic neurons [84], the involvement of gephyrin and the plasticity mechanisms observed here may differ depending on the specific GABAergic synaptic subtype.
The receptor type studied above is the GABAAR α-subunit, which is regulated by gephyrin [134,135]. However, some evidence has also shown that not only the GABAAR α-subunit could regulate iLTP but also CaMKII-dependent-phospho-GABAAR-β3-Ser383, which promotes the accumulation of a scaffold protein (gephyrin) to induce chem-iLTP expression [136]. Additionally, metabotropic GABABR [38,137,138,139,140] and other subtypes of GABAergic synapses [141] are related to the regulation of synaptic plasticity. There is evidence that iLTP induced by GABABR could enhance the depression of excitatory synapses and selectively weaken excitatory input, an anticorrelated plasticity interaction [142]. Therefore, the plasticity of excitatory and inhibitory neurons appears to be interactive rather than independent. The interplay suggests that future research into the relationship between other subtypes of GABAergic synapses and receptors with excitatory neurons deserves further investigation.

5. Discussion

Combining electrophysiological recordings and techniques such as pharmacology, two-photon uncaging, and optogenetics can help better understand the mechanisms involved in LTP induction. Two-photon uncaging exploits the inherent optical sectioning ability of two-photon excitation to generate highly localized increases in neurotransmitter concentrations; e.g., long-term plasticity can be induced by elevated intracellular calcium concentrations generated by the photolysis of caged calcium [143,144,145]. Kano et al. used in vivo two-photon photocleavage of glutamate to find that the structure and movement of mouse cortical dendritic spines are closely related to their rapid glutamate sensing and intracellular calcium increase [146]. With the development of caged compound technology, the application of two-photon uncaging pairs in vivo to study molecular physiological processes at the single-synapse level will continue to deepen, which makes the use of two-photon glutamate uncaging to induce structural and functional LTP dendritic spines possible [147,148]. Compared to traditional single-photon imaging, two-photon imaging has a higher signal-to-noise ratio and spatial resolution, a better signal-to-noise ratio, and less tissue damage [149,150,151]. In addition to being able to monitor physiological phenomena and processes such as neural cell structure, ion concentration, cell movement, and molecular interactions at the cellular or even subcellular level, the two-photon microscope also has many precise optical manipulation functions (such as photolysis, photoactivation, phototransduction, and photodamage).
In addition, optogenetics is used to effectively express light-sensing genes in target neurons to control the activities of selected cells in highly heterogeneous tissues. Further, under the stimulation of a certain wavelength, it can selectively stimulate ions and express through special ion channels, resulting in depolarization or superization of membrane potential to excite or inhibit cells. It can control the number of ions across the membrane and change the resting potential to cause an action potential and selectively induce long-term potentiation (LTP) using optogenetics [57,152,153,154,155]. Matt Udakis et al. used optogenetics to dendrite-targeted inhibition of hippocampal CA1 pyramidal neurons and demonstrated Parvalbumin (PV) and Somatostatin (SST) inhibitory synapses have different plasticity (PV-iLTD and SST-iLTP), which are due to the employment of different signaling mechanisms (e.g., the relative timing of inhibitory and excitatory neuronal spiking) [156]. Yifeng Cheng et al. reported using optogenetics to induce LTP of the OFC→DMS pathway by exposing rats to blue light pulses through optical fibers [57]. Moreover, the latest report showed GPR173: a novel CCK receptor involved in the iLTP of CCK-INs in the cortex [58]. Ling He et al. combine optogenetics with in vivo electrophysiology to illustrate optogenetic laser stimulation of GABAergic neurons suppressed AC neuronal responses to the auditory stimulus [58]. Optogenetic technology cannot only accurately and precisely activate or inhibit specific neurons but also has high temporal and spatial resolution and reversibility benefits. An efficient combination of optogenetics and electrophysiological techniques was used to study the function of particular neuron types and circuits in LTP induction.
As shown in Table 1, most experimental designs used a single-type electrophysiological recording in combination with other forms of experimental techniques to explore a single-type synapse of LTP. The state of the circuit can change the synaptic learning principles used to induce LTP. Neuromodulators can change all network activities, the threshold and time window of plasticity induction, and even switch the plasticity marker from LTP to LTD. It is necessary to design different LTP induction protocols according to different requirements [157,158]. Therefore, the balance mechanism of excitatory and inhibitory synapses should be studied together, which may become a future design direction for electrophysiological experiments. It may also be possible to record excitatory and inhibitory neuronal activity simultaneously using field potentials and whole-cell models and simultaneously explore the activity of different types of synapses in the whole environment. The importance of excitatory synaptic LTP measured by field potentials is unquestionable; however, the role of inhibitory interneurons should not be ignored. Understanding the mechanisms of GABAergic synaptic plasticity is critical for assessing their critical role in CNS function and is fundamental to understanding the problems associated with LTP in various activities [159]. Controlling GABAergic synaptic strength is an important and growing area of research.
It is widely accepted that LTP, resulting in synaptic modifications caused by physiological stimuli, correlates with learning and memory formation [92]. Recently, there have been increasing investigations of electrically stimulated LTP observed at inhibitory synapses in different brain areas, including the hippocampus, although most are observed at excitatory synapses previously [93]. Researchers have demonstrated that excitatory LTP provides a more effective detection, while iLTP maintains the temporal resolution of the neuronal network by using a whole-cell patch clamp [94]. It means that the excitatory LTP is dominant for short stimulation intervals due to significant increases in spike generation. Still, inhibitory LTP has an important role in preventing the degradation of this time window.
Recent studies have developed analytical methods to measure excitatory and inhibitory inputs [139] simultaneously. More specifically, both voltage clamp and current clamp recordings can be used to compute evoked LTP in vivo or in vitro [160]. For the voltage clamp measurements, it is understandable to disintegrate excitatory and inhibitory inputs directly by the linear system resolution [161]. Assuming that the regression model of the I/V curve between resting potential and the peak of activation in the voltage clamp is linear, the evoked synaptic conductance can be measured by either the linear part or the full range of the I/V curve [162]. In addition, to decrease the rectification error, researchers also utilize the polynomial regression model to the synaptic or full I/V curve. In this case, the LTP is considered the variance between the global conductance, correlated to a zero current value, and the resting conductance is measured by the tangent to the I/V curve at the resting potential. In the same way, the measurement of evoked LTP in current-clamp recordings is completed but with a current clamp mode, injecting constant currents with membrane potential near the reversal potential of inputs [160].
Long-term depression has been shown to reverse LTP in some synapses [163], resulting in use-dependent bidirectional changes [164]. Similarly, we can hypothesize that the increase in the population EPSP signal of LTP is excitatory enhanced due to a decrease in inhibitory signal or both. Excitation and inhibition are inextricably linked to time and space in the brain. Therefore, subtle changes in balance are linked to both neurological disease development, such as Alzheimer’s and Parkinson’s disease, and behavior [165,166,167,168]. Interrupting this dynamic balance between excitation and inhibition can significantly impact the creature’s life stability and flexibility. Therefore, these aspects deserve to be explored in greater detail in the future.
Various forms of synaptic plasticity have been shown to exist. Spike timing-dependent plasticity (STDP), a phenomenon affecting sign and magnitude of synaptic strength changes through precise spikes, is a major mechanism of the brain’s ability to learn and form new memories [169]. STDP has been demonstrated to depend on target and synaptic location and is also affected by the activity of neighboring synapses, the presence of postsynaptic calcium, presynaptic GABA inhibition, and neuromodulator dynamic adjustment [169,170,171]. Homeostatic synaptic plasticity: as a specific form of synaptic plasticity, homeostatic synaptic plasticity refers to the ability of neurons to regulate their excitability relative to network activity to maintain network homeostasis amid long-term changes in neuronal activity [172]. These different synaptic plasticities combine in complex ways to affect local circuit computation. These forms of plasticity also coexist with homeostatic mechanisms to maintain circuit function despite potentially destabilizing perturbations [89]. The coexistence of multiple forms of plasticity may reflect the hierarchical processing of information, possibly allowing the ordering of memories according to their salience [173].
Moreover, aging is thought to cause cognitive decline, which could be explained by changes in age-dependent synaptic plasticity or cellular alterations directly affecting plasticity mechanisms [174,175]. Lik-Wei Wong et al. report that the p75 neurotrophin receptor (p75NTR) may represent an important therapeutic target for limiting age-related deficits in memory and cognitive function [176]. Alexander et al. demonstrated that the perisynaptic astrocyte contraction and contraction of the processes give way to glutamate spillover. Age-dependent learning and memory impairments are possibly due to impaired synaptic plasticity [56]. Therefore, these could help better understand the age-related decline in learning and memory. Not just age but the latest evidence of Sian Lewis’ report refers to the sharing and differential expression of transcriptome-defining markers in various neurons and glia across species [177]. These results show that cells’ neurogenic potential in the hippocampal formation varies between species.
Recent studies discovered that glial cells contribute to neuronal function by regulating extracellular K+ levels, leading to different CNS diseases [178]. It is reported that, in animal models of Rett syndrome (RTT), a neurodevelopmental disorder mostly due to mutations in the X-linked transcriptional regulator methyl CpG binding protein 2 (MeCP2), symptoms can be improved or prevented by re-expression of MeCP2 merely in astrocytes [179] What is more, the glia cells also have a strong impact in Huntington’s disease (HD), a neuronal disease usually associated with neuronal dysfunction and atrophy of the striatum and other brain areas. Evidence suggests that K+ ion channel expression was decreased in astrocytes expressing mutant huntingtin (mHTT). In contrast, the astrocyte glutamate transporter Glt1 expression was rescued by restoring the loss of K+ expression in glial cells, which has a strong relationship with the development of HD [180]. In pathological conditions such as Alzheimer’s disease (AD), some astrocyte neurotransmitters, such as GABA, show abnormal levels. It is observed in several studies that astrocytic GABA was elevated in the AD model [181]. In conclusion, these studies demonstrated that astrocytes are crucial for discovering the mechanisms of neurological and psychiatric diseases as the most numerous cells in the CNS. These aspects deserve to be explored in greater detail in the future.

Author Contributions

Conceptualization, F.J. and L.H.; writing—original draft preparation, F.J.; writing—review and editing, F.J., S.T.B., Q.G., L.H. and Y.L.; supervision, L.H. and X.L. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by the following: Hong Kong Research Grants Council, Collaborative Research Fund: C1014-15g, C7048-16g; C1043-21 GF (CRF, JFH).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

The authors thank Jufang He for critical comments and generous support, as well as Dingxuan Zeng, Changwei Lai and Abdul Waris in our lab at the City University of Hong Kong for technical suggestions during the revision.

Conflicts of Interest

The authors declare no conflict of interest.

Abbreviations

LTPLong-term potentiation
iLTPLong-term potentiation of the inhibitory synapses
Chem-iLTPChemically induced iLTP
EPSPExcitatory postsynaptic potential
IPSCInhibitory postsynaptic current
HPHippocampus
VTAVentral tegmental area
HFSHigh-frequency stimulation
SCStellate cells
PKCProtein kinase C
CaMKIICalcium–calmodulin (CaM) dependent protein kinase II
PKAProtein kinase A system
BDNF-TrkBBrain-derived neurotrophic factor_ Tyrosine kinase B
NMDARN-methyl-D-aspartate receptor
GABAγ-aminobutyric acid
GABAARGABA A receptor
GABABRGABA B receptor
cGMPCyclic guanosine monophosphate
PUTPolyamine putrescine
SPMPolyamine spermine
APsAction potentials
LFPsLocal field potentials
edNEGElectrodiffusive neuron-extracellular-glia
MEAmicroelectrode array
CNScentral nervous system
Trktyrosine-related receptor kinase
STDPSpike timing-dependent plasticity
MeCP2methyl CpG binding protein 2
mHTTmutant huntingtin
HDHuntington’s disease
ADAlzheimer’s disease
mHTTmutant huntingtin
p75NTRp75 neurotrophin receptor
ACCAnterior cingulate cortex
oEPSCsOptically evoked excitatory postsynaptic currents
oHFSOptogenetic HFS
HFLSHigh-frequency laser stimulation
CCKRCholecystokinin receptor
PUTputrescine
LTPCCKA form of activity-dependent synaptic plasticity mediated by CCK
ACAuditory cortex

References

  1. Herculano-Houzel, S.; Lent, R. Isotropic fractionator: A simple, rapid method for the quantification of total cell and neuron numbers in the brain. J. Neurosci. 2005, 25, 2518–2521. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  2. Charvet, C.J.; Cahalane, D.J.; Finlay, B.L. Systematic, cross-cortex variation in neuron numbers in rodents and primates. Cereb. Cortex 2015, 25, 147–160. [Google Scholar] [CrossRef] [PubMed]
  3. Herculano-Houzel, S.; Mota, B.; Lent, R. Cellular scaling rules for rodent brains. Proc. Natl. Acad. Sci. USA 2006, 103, 12138–12143. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  4. Lent, R.; Azevedo, F.A.; Andrade-Moraes, C.H.; Pinto, A.V. How many neurons do you have? Some dogmas of quantitative neuroscience under revision. Eur. J. Neurosci. 2012, 35, 1–9. [Google Scholar] [CrossRef] [PubMed]
  5. Magee, J.C.; Grienberger, C. Synaptic Plasticity Forms and Functions. Annu. Rev. Neurosci. 2020, 43, 95–117. [Google Scholar] [CrossRef] [Green Version]
  6. Nayak, M.; Das, D.; Pradhan, J.; Ahmed, R.; Laureano-Melo, R.; Dandapat, J. Epigenetic signature in neural plasticity: The journey so far and journey ahead. Heliyon 2022, 8, e12292. [Google Scholar] [CrossRef]
  7. Trojan, S.; Pokorny, J. Threoretical aspects of neuroplasticity. Physiol. Res. 1999, 48, 87–98. [Google Scholar]
  8. Martin, S.J.; Grimwood, P.D.; Morris, R.G. Synaptic plasticity and memory: An evaluation of the hypothesis. Annu. Rev. Neurosci. 2000, 23, 649–711. [Google Scholar] [CrossRef] [Green Version]
  9. Matynia, A.; Kushner, S.A.; Silva, A.J. Genetic approaches to molecular and cellular cognition: A focus on LTP and learning and memory. Annu. Rev. Genet. 2002, 36, 687–720. [Google Scholar] [CrossRef] [Green Version]
  10. Bliss, T.V.; Lomo, T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J. Physiol. 1973, 232, 331–356. [Google Scholar] [CrossRef]
  11. Abraham, W.C. How long will long-term potentiation last? Philos. Trans. R. Soc. Lond. B Biol. Sci. 2003, 358, 735–744. [Google Scholar] [CrossRef]
  12. Henze, D.A.; Borhegyi, Z.; Csicsvari, J.; Mamiya, A.; Harris, K.D.; Buzsáki, G. Intracellular features predicted by extracellular recordings in the hippocampus in vivo. J. Neurophysiol. 2000, 84, 390–400. [Google Scholar] [CrossRef]
  13. Oka, H.; Shimono, K.; Ogawa, R.; Sugihara, H.; Taketani, M. A new planar multielectrode array for extracellular recording: Application to hippocampal acute slice. J. Neurosci. Methods 1999, 93, 61–67. [Google Scholar] [CrossRef] [PubMed]
  14. Neher, E.; Sakmann, B. The patch clamp technique. Sci. Am. 1992, 266, 44–51. [Google Scholar] [CrossRef] [PubMed]
  15. Lomo, T. Frequency Potentiation of Excitatory Synaptic Activity in Dentate Area of Hippocampal Formation; Acta Physiologica Scandinavica, 1966; Blackwell Science Ltd.: Oxford, UK, 1966; p. 128. [Google Scholar]
  16. Schwartzkroin, P.A.; Wester, K. Long-lasting facilitation of a synaptic potential following tetanization in the in vitro hippocampal slice. Brain Res. 1975, 89, 107–119. [Google Scholar] [CrossRef]
  17. Dunwiddie, T.; Madison, D.; Lynch, G. Synaptic transmission is required for initiation of long-term potentiation. Brain Res. 1978, 150, 413–417. [Google Scholar] [CrossRef] [PubMed]
  18. Dunwiddie, T.V.; Lynch, G. The relationship between extracellular calcium concentrations and the induction of hippocampal long-term potentiation. Brain Res. 1979, 169, 103–110. [Google Scholar] [CrossRef]
  19. Collingridge, G.L.; Kehl, S.; McLennan, H. The antagonism of amino acid-induced excitations of rat hippocampal CA1 neurones in vitro. J. Physiol. 1983, 334, 19–31. [Google Scholar] [CrossRef] [PubMed]
  20. Muller, D.; Joly, M.; Lynch, G. Contributions of quisqualate and NMDA receptors to the induction and expression of LTP. Science 1988, 242, 1694–1697. [Google Scholar] [CrossRef]
  21. Davies, J.; Francis, A.A.; Jones, A.W.; Watkins, J.C. 2-Amino-5-phosphonovalerate (2APV), a potent and selective antagonist of amino acid-induced and synaptic excitation. Neurosci. Lett. 1981, 21, 77–81. [Google Scholar] [CrossRef]
  22. Lynch, G.; Baudry, M. The biochemistry of memory: A new and specific hypothesis. Science 1984, 224, 1057–1063. [Google Scholar] [CrossRef]
  23. Stelzer, A.; Slater, N.T.; ten Bruggencate, G. Activation of NMDA receptors blocks GABAergic inhibition in an in vitro model of epilepsy. Nature 1987, 326, 698–701. [Google Scholar] [CrossRef]
  24. Artola, A.; Singer, W. Long-term potentiation and NMDA receptors in rat visual cortex. Nature 1987, 330, 649–652. [Google Scholar] [CrossRef]
  25. Chavez-Noriega, L.E.; Halliwell, J.V.; Bliss, T.V. A decrease in firing threshold observed after induction of the EPSP-spike (E-S) component of long-term potentiation in rat hippocampal slices. Exp. Brain Res. 1990, 79, 633–641. [Google Scholar] [CrossRef]
  26. Davies, C.H.; Starkey, S.J.; Pozza, M.F.; Collingridge, G.L. GABA autoreceptors regulate the induction of LTP. Nature 1991, 349, 609–611. [Google Scholar] [CrossRef] [PubMed]
  27. Mott, D.D.; Lewis, D.V. Facilitation of the induction of long-term potentiation by GABAB receptors. Science 1991, 252, 1718–1720. [Google Scholar] [CrossRef]
  28. Bashir, Z.I.; Bortolotto, Z.A.; Davies, C.H.; Berretta, N.; Irving, A.J.; Seal, A.J.; Henley, J.M.; Jane, D.E.; Watkins, J.C.; Collingridge, G.L. Induction of LTP in the hippocampus needs synaptic activation of glutamate metabotropic receptors. Nature 1993, 363, 347–350. [Google Scholar] [CrossRef]
  29. Bortolotto, Z.A.; Bashir, Z.I.; Davies, C.H.; Collingridge, G.L. A molecular switch activated by metabotropic glutamate receptors regulates induction of long-term potentiation. Nature 1994, 368, 740–743. [Google Scholar] [CrossRef] [PubMed]
  30. Bliss, T.V.; Collingridge, G.L. A synaptic model of memory: Long-term potentiation in the hippocampus. Nature 1993, 361, 31–39. [Google Scholar] [CrossRef]
  31. Williams, J.H.; Li, Y.G.; Nayak, A.; Errington, M.L.; Murphy, K.P.; Bliss, T.V. The suppression of long-term potentiation in rat hippocampus by inhibitors of nitric oxide synthase is temperature and age dependent. Neuron 1993, 11, 877–884. [Google Scholar] [CrossRef] [PubMed]
  32. Komatsu, Y. Age-dependent long-term potentiation of inhibitory synaptic transmission in rat visual cortex. J. Neurosci. 1994, 14 Pt 1, 6488–6499. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  33. Komatsu, Y. GABAB receptors, monoamine receptors, and postsynaptic inositol trisphosphate-induced Ca2+ release are involved in the induction of long-term potentiation at visual cortical inhibitory synapses. J. Neurosci. 1996, 16, 6342–6352. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  34. Grunze, H.C.; Rainnie, D.G.; Hasselmo, M.E.; Barkai, E.; Hearn, E.F.; McCarley, R.W.; Greene, R.W. NMDA-dependent modulation of CA1 local circuit inhibition. J. Neurosci. 1996, 16, 2034–2043. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  35. McLean, H.A.; Caillard, O.; Ben-Ari, Y.; Gaiarsa, J.L. Bidirectional plasticity expressed by GABAergic synapses in the neonatal rat hippocampus. J. Physiol. 1996, 496 Pt 2, 471–477. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  36. Arancio, O.; Kiebler, M.; Lee, C.J.; Lev-Ram, V.; Tsien, R.Y.; Kandel, E.R.; Hawkins, R.D. Nitric oxide acts directly in the presynaptic neuron to produce long-term potentiation in cultured hippocampal neurons. Cell 1996, 87, 1025–1035. [Google Scholar] [CrossRef] [Green Version]
  37. Caillard, O.; Ben-Ari, Y.; Gaiarsa, J.L. Long-term potentiation of GABAergic synaptic transmission in neonatal rat hippocampus. J. Physiol. 1999, 518 Pt 1, 109–119. [Google Scholar] [CrossRef] [PubMed]
  38. Patenaude, C.; Chapman, C.A.; Bertrand, S.; Congar, P.; Lacaille, J.C. GABAB receptor- and metabotropic glutamate receptor-dependent cooperative long-term potentiation of rat hippocampal GABAA synaptic transmission. J. Physiol. 2003, 553 Pt 1, 155–167. [Google Scholar] [CrossRef]
  39. Bauer, E.P.; LeDoux, J.E. Heterosynaptic long-term potentiation of inhibitory interneurons in the lateral amygdala. J. Neurosci. 2004, 24, 9507–9512. [Google Scholar] [CrossRef] [Green Version]
  40. Maffei, A.; Nataraj, K.; Nelson, S.B.; Turrigiano, G.G. Potentiation of cortical inhibition by visual deprivation. Nature 2006, 443, 81–84. [Google Scholar] [CrossRef]
  41. Nugent, F.S.; Penick, E.C.; Kauer, J.A. Opioids block long-term potentiation of inhibitory synapses. Nature 2007, 446, 1086–1090. [Google Scholar] [CrossRef]
  42. Inagaki, T.; Begum, T.; Reza, F.; Horibe, S.; Inaba, M.; Yoshimura, Y.; Komatsu, Y. Brain-derived neurotrophic factor-mediated retrograde signaling required for the induction of long-term potentiation at inhibitory synapses of visual cortical pyramidal neurons. Neurosci. Res. 2008, 61, 192–200. [Google Scholar] [CrossRef] [PubMed]
  43. Nugent, F.S.; Niehaus, J.L.; Kauer, J.A. PKG and PKA signaling in LTP at GABAergic synapses. Neuropsychopharmacology 2009, 34, 1829–1842. [Google Scholar] [CrossRef] [PubMed]
  44. Sarihi, A.; Jiang, B.; Komaki, A.; Sohya, K.; Yanagawa, Y.; Tsumoto, T. Metabotropic glutamate receptor type 5-dependent long-term potentiation of excitatory synapses on fast-spiking GABAergic neurons in mouse visual cortex. J. Neurosci. 2008, 28, 1224–1235. [Google Scholar] [CrossRef] [Green Version]
  45. Sivakumaran, S.; Mohajerani, M.H.; Cherubini, E. At immature mossy-fiber-CA3 synapses, correlated presynaptic and postsynaptic activity persistently enhances GABA release and network excitability via BDNF and cAMP-dependent PKA. J. Neurosci. 2009, 29, 2637–2647. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  46. Perea, G.; Araque, A. Astrocytes potentiate transmitter release at single hippocampal synapses. Science 2007, 317, 1083–1086. [Google Scholar] [CrossRef]
  47. Henneberger, C.; Papouin, T.; Oliet, S.H.; Rusakov, D.A. Long-term potentiation depends on release of D-serine from astrocytes. Nature 2010, 463, 232–236. [Google Scholar] [CrossRef] [PubMed]
  48. Yang, Y.; Ge, W.; Chen, Y.; Zhang, Z.; Shen, W.; Wu, C.; Poo, M.; Duan, S. Contribution of astrocytes to hippocampal long-term potentiation through release of D-serine. Proc. Natl. Acad. Sci. USA 2003, 100, 15194–15199. [Google Scholar] [CrossRef] [Green Version]
  49. Xu, H.; Kotak, V.C.; Sanes, D.H. Normal hearing is required for the emergence of long-lasting inhibitory potentiation in cortex. J. Neurosci. 2010, 30, 331–341. [Google Scholar] [CrossRef] [Green Version]
  50. Crosby, K.M.; Murphy-Royal, C.; Wilson, S.A.; Gordon, G.R.; Bains, J.S.; Pittman, Q.J. Cholecystokinin Switches the Plasticity of GABA Synapses in the Dorsomedial Hypothalamus via Astrocytic ATP Release. J. Neurosci. 2018, 38, 8515–8525. [Google Scholar] [CrossRef] [Green Version]
  51. Chen, X.; Li, X.; Wong, Y.T.; Zheng, X.; Wang, H.; Peng, Y.; Feng, H.; Feng, J.; Baibado, J.T.; Jesky, R.; et al. Cholecystokinin release triggered by NMDA receptors produces LTP and sound-sound associative memory. Proc. Natl. Acad. Sci. USA 2019, 116, 6397–6406. [Google Scholar] [CrossRef] [Green Version]
  52. Ma, T.; Cheng, Y.; Roltsch Hellard, E.; Wang, X.; Lu, J.; Gao, X.; Huang, C.C.Y.; Wei, X.Y.; Ji, J.Y.; Wang, J. Bidirectional and long-lasting control of alcohol-seeking behavior by corticostriatal LTP and LTD. Nat. Neurosci. 2018, 21, 373–383. [Google Scholar] [CrossRef]
  53. Lee, H.U.; Yamazaki, Y.; Tanaka, K.F.; Furuya, K.; Sokabe, M.; Hida, H.; Takao, K.; Miyakawa, T.; Fujii, S.; Ikenaka, K. Increased astrocytic ATP release results in enhanced excitability of the hippocampus. Glia 2013, 61, 210–224. [Google Scholar] [CrossRef]
  54. Martinez Damonte, V.; Pomrenze, M.B.; Manning, C.E.; Casper, C.; Wolfden, A.L.; Malenka, R.C.; Kauer, J.A. Somatodendritic Release of Cholecystokinin Potentiates GABAergic Synapses Onto Ventral Tegmental Area Dopamine Cells. Biol. Psychiatry 2023, 93, 197–208. [Google Scholar] [CrossRef]
  55. Ravasenga, T.; Ruben, M.; Regio, V.; Polenghi, A.; Petrini, E.M.; Barberis, A. Spatial regulation of coordinated excitatory and inhibitory synaptic plasticity at dendritic synapses. Cell Rep. 2022, 38, 110347. [Google Scholar] [CrossRef]
  56. Popov, A.; Brazhe, A.; Denisov, P.; Sutyagina, O.; Li, L.; Lazareva, N.; Verkhratsky, A.; Semyanov, A. Astrocyte dystrophy in ageing brain parallels impaired synaptic plasticity. Aging Cell 2021, 20, e13334. [Google Scholar] [CrossRef] [PubMed]
  57. Cheng, Y.; Xie, X.; Lu, J.; Gangal, H.; Wang, W.; Melo, S.; Wang, X.; Jerger, J.; Woodson, K.; Garr, E.; et al. Optogenetic induction of orbitostriatal long-term potentiation in the dorsomedial striatum elicits a persistent reduction of alcohol-seeking behavior in rats. Neuropharmacology 2021, 191, 108560. [Google Scholar] [CrossRef] [PubMed]
  58. He, L.; Shi, H.; Zhang, G.; Peng, Y.; Ghosh, A.; Zhang, M.; Hu, X.; Liu, C.; Shao, Y.; Wang, S.; et al. A Novel CCK Receptor GPR173 Mediates Potentiation of GABAergic Inhibition. J. Neurosci. 2023, 43, 2305–2325. [Google Scholar] [CrossRef]
  59. Scott, H.L.; Bolmatov, D.; Podar, P.T.; Liu, Z.; Kinnun, J.J.; Doughty, B.; Lydic, R.; Sacci, R.L.; Collier, C.P.; Katsaras, J. Evidence for long-term potentiation in phospholipid membranes. Proc. Natl. Acad. Sci. USA 2022, 119, e2212195119. [Google Scholar] [CrossRef] [PubMed]
  60. Lømo, T. The discovery of long-term potentiation. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2003, 358, 617–620. [Google Scholar] [CrossRef] [Green Version]
  61. Kimura, F.; Nishigori, A.; Shirokawa, T.; Tsumoto, T. Long-term potentiation and N-methyl-D-aspartate receptors in the visual cortex of young rats. J. Physiol. 1989, 414, 125–144. [Google Scholar] [CrossRef]
  62. Grover, L.M.; Teyler, T.J. Two components of long-term potentiation induced by different patterns of afferent activation. Nature 1990, 347, 477–479. [Google Scholar] [CrossRef]
  63. Zakharenko, S.S.; Zablow, L.; Siegelbaum, S.A. Visualization of changes in presynaptic function during long-term synaptic plasticity. Nat. Neurosci. 2001, 4, 711–717. [Google Scholar] [CrossRef] [PubMed]
  64. Gross, G.W.; Williams, A.N.; Lucas, J.H. Recording of spontaneous activity with photoetched microelectrode surfaces from mouse spinal neurons in culture. J. Neurosci. Methods 1982, 5, 13–22. [Google Scholar] [CrossRef] [PubMed]
  65. Garad, M.; Edelmann, E.; Leßmann, V. Impairment of Spike-Timing-Dependent Plasticity at Schaffer Collateral-CA1 Synapses in Adult APP/PS1 Mice Depends on Proximity of Aβ Plaques. Int. J. Mol. Sci. 2021, 22, 1378. [Google Scholar] [CrossRef]
  66. Liu, Y.; Ding, S.; Luan, Y.; Zhu, Z.; Cai, Y.; Liu, Y. Ginkgo biloba extracts inhibit post-ischemic LTP through attenuating EPSCs in rat hippocampus. Metab. Brain Dis. 2021, 36, 2299–2311. [Google Scholar] [CrossRef] [PubMed]
  67. Griego, E.; Galván, E.J. Biophysical and synaptic properties of regular spiking interneurons in hippocampal area CA3 of aged rats. Neurobiol. Aging 2022, 112, 27–38. [Google Scholar] [CrossRef] [PubMed]
  68. Segev, A.; Garcia-Oscos, F.; Kourrich, S. Whole-cell Patch-clamp Recordings in Brain Slices. J. Vis. Exp. 2016, 112, e54024. [Google Scholar] [CrossRef]
  69. Erofeev, A.; Antifeev, I.; Bolshakova, A.; Bezprozvanny, I.; Vlasova, O. In Vivo Penetrating Microelectrodes for Brain Electrophysiology. Sensors 2022, 22, 9085. [Google Scholar] [CrossRef]
  70. Kirkwood, A.; Dudek, S.M.; Gold, J.T.; Aizenman, C.D.; Bear, M.F. Common forms of synaptic plasticity in the hippocampus and neocortex in vitro. Science 1993, 260, 1518–1521. [Google Scholar] [CrossRef]
  71. Wang, X.F.; Daw, N.W. Long term potentiation varies with layer in rat visual cortex. Brain Res. 2003, 989, 26–34. [Google Scholar] [CrossRef]
  72. Liu, H.N.; Kurotani, T.; Ren, M.; Yamada, K.; Yoshimura, Y.; Komatsu, Y. Presynaptic activity and Ca2+ entry are required for the maintenance of NMDA receptor-independent LTP at visual cortical excitatory synapses. J. Neurophysiol. 2004, 92, 1077–1087. [Google Scholar] [CrossRef] [Green Version]
  73. Huemmeke, M.; Eysel, U.T.; Mittmann, T. Metabotropic glutamate receptors mediate expression of LTP in slices of rat visual cortex. Eur. J. Neurosci. 2002, 15, 1641–1645. [Google Scholar] [CrossRef] [PubMed]
  74. Newman, E.A.; Frambach, D.A.; Odette, L.L. Control of extracellular potassium levels by retinal glial cell K+ siphoning. Science 1984, 225, 1174–1175. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  75. Bykov, K.A.; Dmitriev, A.V.; Skachkov, S.N. Relationship between photoinduced changes in the intercellular concentration of potassium ions and transretinal potential generation by the Muller cells of the retina. Biofizika 1981, 26, 104–107. [Google Scholar] [PubMed]
  76. Newman, E.A.; Odette, L.L. Model of electroretinogram b-wave generation: A test of the K+ hypothesis. J. Neurophysiol. 1984, 51, 164–182. [Google Scholar] [CrossRef] [Green Version]
  77. Karwoski, C.J.; Lu, H.K.; Newman, E.A. Spatial buffering of light-evoked potassium increases by retinal Muller (glial) cells. Science 1989, 244, 578–580. [Google Scholar] [CrossRef] [PubMed]
  78. Kuroda, T.; Matsuda, N.; Ishibashi, Y.; Suzuki, I. Detection of astrocytic slow oscillatory activity and response to seizurogenic compounds using planar microelectrode array. Front. Neurosci. 2022, 16, 1050150. [Google Scholar] [CrossRef]
  79. Sætra, M.J.; Einevoll, G.T.; Halnes, G. An electrodiffusive neuron-extracellular-glia model for exploring the genesis of slow potentials in the brain. PLoS Comput. Biol. 2021, 17, e1008143. [Google Scholar] [CrossRef]
  80. Abraham, W.C.; Gustafsson, B.; Wigström, H. Long-term potentiation involves enhanced synaptic excitation relative to synaptic inhibition in guinea-pig hippocampus. J. Physiol. 1987, 394, 367–380. [Google Scholar] [CrossRef] [Green Version]
  81. Gray, R.; Johnston, D. Noradrenaline and beta-adrenoceptor agonists increase activity of voltage-dependent calcium channels in hippocampal neurons. Nature 1987, 327, 620–622. [Google Scholar] [CrossRef]
  82. Edwards, F.A.; Konnerth, A.; Sakmann, B.; Takahashi, T. A thin slice preparation for patch clamp recordings from neurones of the mammalian central nervous system. Pflug. Arch. 1989, 414, 600–612. [Google Scholar] [CrossRef]
  83. Tepper, J.M.; Bolam, J.P. Functional diversity and specificity of neostriatal interneurons. Curr. Opin. Neurobiol. 2004, 14, 685–692. [Google Scholar] [CrossRef]
  84. Gonchar, Y.; Wang, Q.; Burkhalter, A. Multiple distinct subtypes of GABAergic neurons in mouse visual cortex identified by triple immunostaining. Front. Neuroanat. 2007, 1, 3. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  85. Ascoli, G.; Alonso-Nanclares, L.; Anderson, S.; Barrionuevo, G.; Benavides-Piccione, R.; Burkhalter, A.; Buzsáki, G.; Cauli, B.; DeFelipe, J.; Fairén, A. Yuste The Petilla Interneuron Nomenclature Group (PING) R. Petilla terminology: Nomenclature of features of GABAergic interneurons of the cerebral cortex. Nat. Rev. Neurosci. 2008, 9, 557–568. [Google Scholar] [PubMed] [Green Version]
  86. Kullmann, D.M.; Lamsa, K.P. LTP and LTD in cortical GABAergic interneurons: Emerging rules and roles. Neuropharmacology 2011, 60, 712–719. [Google Scholar] [CrossRef] [PubMed]
  87. Kittler, J.T.; Moss, S.J. Modulation of GABAA receptor activity by phosphorylation and receptor trafficking: Implications for the efficacy of synaptic inhibition. Curr. Opin. Neurobiol. 2003, 13, 341–347. [Google Scholar] [CrossRef] [PubMed]
  88. Castillo, P.E. Presynaptic LTP and LTD of excitatory and inhibitory synapses. Cold Spring Harb. Perspect. Biol. 2012, 4, a005728. [Google Scholar] [CrossRef] [Green Version]
  89. Monday, H.R.; Younts, T.J.; Castillo, P.E. Long-Term Plasticity of Neurotransmitter Release: Emerging Mechanisms and Contributions to Brain Function and Disease. Annu. Rev. Neurosci. 2018, 41, 299–322. [Google Scholar] [CrossRef]
  90. Bauer, V.; Sotníková, R. Nitric oxide—The endothelium-derived relaxing factor and its role in endothelial functions. Gen. Physiol. Biophys. 2010, 29, 319. [Google Scholar] [CrossRef] [Green Version]
  91. Jobgen, W.S.; Wu, G. l-Arginine increases AMPK phosphorylation and the oxidation of energy substrates in hepatocytes, skeletal muscle cells, and adipocytes. Amino Acids 2022, 54, 1553–1568. [Google Scholar] [CrossRef] [PubMed]
  92. Huang, E.P. Synaptic plasticity: A role for nitric oxide in LTP. Curr. Biol. 1997, 7, R141–R143. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  93. Tropea, M.R.; Gulisano, W.; Vacanti, V.; Arancio, O.; Puzzo, D.; Palmeri, A. Nitric oxide/cGMP/CREB pathway and amyloid-beta crosstalk: From physiology to Alzheimer’s disease. Free Radic. Biol. Med. 2022, 193 Pt 2, 657–668. [Google Scholar] [CrossRef]
  94. Jehle, A.; Garaschuk, O. The Interplay between cGMP and Calcium Signaling in Alzheimer’s Disease. Int. J. Mol. Sci. 2022, 23, 7048. [Google Scholar] [CrossRef] [PubMed]
  95. Niehaus, J.L.; Murali, M.; Kauer, J.A. Drugs of abuse and stress impair LTP at inhibitory synapses in the ventral tegmental area. Eur. J. Neurosci. 2010, 32, 108–117. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  96. O’Dell, T.J.; Hawkins, R.D.; Kandel, E.R.; Arancio, O. Tests of the roles of two diffusible substances in long-term potentiation: Evidence for nitric oxide as a possible early retrograde messenger. Proc. Natl. Acad. Sci. USA 1991, 88, 11285–11289. [Google Scholar] [CrossRef] [Green Version]
  97. Ge, Y.-X.; Xin, W.-J.; Hu, N.-W.; Zhang, T.; Xu, J.-T.; Liu, X.-G. Clonidine depresses LTP of C-fiber evoked field potentials in spinal dorsal horn via NO-cGMP pathway. Brain Res. 2006, 1118, 58–65. [Google Scholar] [CrossRef]
  98. Alkadhi, K.; Alzoubi, K.; Aleisa, A. Plasticity of synaptic transmission in autonomic ganglia. Prog. Neurobiol. 2005, 75, 83–108. [Google Scholar] [CrossRef]
  99. Acquarone, E.; Argyrousi, E.K.; Van Den Berg, M.; Gulisano, W.; Fà, M.; Staniszewski, A.; Calcagno, E.; Zuccarello, E.; D’Adamio, L.; Deng, S.-X. Synaptic and memory dysfunction induced by tau oligomers is rescued by up-regulation of the nitric oxide cascade. Mol. Neurodegener. 2019, 14, 26. [Google Scholar] [CrossRef]
  100. Argyrousi, E.K.; Heckman, P.R.; Prickaerts, J. Role of cyclic nucleotides and their downstream signaling cascades in memory function: Being at the right time at the right spot. Neurosci. Biobehav. Rev. 2020, 113, 12–38. [Google Scholar] [CrossRef]
  101. Chachlaki, K.; Prevot, V. Nitric oxide signalling in the brain and its control of bodily functions. Br. J. Pharmacol. 2020, 177, 5437–5458. [Google Scholar] [CrossRef]
  102. Lu, B. BDNF and activity-dependent synaptic modulation. Learn. Mem. 2003, 10, 86–98. [Google Scholar] [CrossRef] [Green Version]
  103. Colucci-D’Amato, L.; Speranza, L.; Volpicelli, F. Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer. Int. J. Mol. Sci. 2020, 21, 7777. [Google Scholar] [CrossRef]
  104. Qiu, L.L.; Pan, W.; Luo, D.; Zhang, G.F.; Zhou, Z.Q.; Sun, X.Y.; Yang, J.J.; Ji, M.H. Dysregulation of BDNF/TrkB signaling mediated by NMDAR/Ca(2+)/calpain might contribute to postoperative cognitive dysfunction in aging mice. J. Neuroinflammation 2020, 17, 23. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  105. Gubellini, P.; Ben-Ari, Y.; Gaïarsa, J.L. Endogenous neurotrophins are required for the induction of GABAergic long-term potentiation in the neonatal rat hippocampus. J. Neurosci. 2005, 25, 5796–5802. [Google Scholar] [CrossRef] [Green Version]
  106. Lessmann, V.; Gottmann, K.; Malcangio, M. Neurotrophin secretion: Current facts and future prospects. Prog. Neurobiol. 2003, 69, 341–374. [Google Scholar] [CrossRef] [PubMed]
  107. Zakharenko, S.S.; Patterson, S.L.; Dragatsis, I.; Zeitlin, S.O.; Siegelbaum, S.A.; Kandel, E.R.; Morozov, A. Presynaptic BDNF required for a presynaptic but not postsynaptic component of LTP at hippocampal CA1-CA3 synapses. Neuron 2003, 39, 975–990. [Google Scholar] [CrossRef] [Green Version]
  108. von Bohlen Und Halbach, O.; von Bohlen Und Halbach, V. BDNF effects on dendritic spine morphology and hippocampal function. Cell. Tissue Res. 2018, 373, 729–741. [Google Scholar] [CrossRef] [PubMed]
  109. Magariños, A.M.; Li, C.J.; Gal Toth, J.; Bath, K.G.; Jing, D.; Lee, F.S.; McEwen, B.S. Effect of brain-derived neurotrophic factor haploinsufficiency on stress-induced remodeling of hippocampal neurons. Hippocampus 2011, 21, 253–264. [Google Scholar] [CrossRef] [Green Version]
  110. Alkadhi, K.A. NMDA receptor-independent LTP in mammalian nervous system. Prog. Neurobiol. 2021, 200, 101986. [Google Scholar] [CrossRef]
  111. Chen, Q.Y.; Li, X.H.; Zhuo, M. NMDA receptors and synaptic plasticity in the anterior cingulate cortex. Neuropharmacology 2021, 197, 108749. [Google Scholar] [CrossRef]
  112. Lachamp, P.M.; Liu, Y.; Liu, S.J. Glutamatergic modulation of cerebellar interneuron activity is mediated by an enhancement of GABA release and requires protein kinase A/RIM1alpha signaling. J. Neurosci. 2009, 29, 381–392. [Google Scholar] [CrossRef] [Green Version]
  113. Liu, S.J.; Lachamp, P. The activation of excitatory glutamate receptors evokes a long-lasting increase in the release of GABA from cerebellar stellate cells. J. Neurosci. 2006, 26, 9332–9339. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  114. Castillo, P.E.; Chiu, C.Q.; Carroll, R.C. Long-term plasticity at inhibitory synapses. Curr. Opin. Neurobiol. 2011, 21, 328–338. [Google Scholar] [CrossRef] [Green Version]
  115. Aizenman, C.D.; Manis, P.B.; Linden, D.J. Polarity of long-term synaptic gain change is related to postsynaptic spike firing at a cerebellar inhibitory synapse. Neuron 1998, 21, 827–835. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  116. Chistiakova, M.; Bannon, N.M.; Bazhenov, M.; Volgushev, M. Heterosynaptic plasticity: Multiple mechanisms and multiple roles. Neuroscientist 2014, 20, 483–498. [Google Scholar] [CrossRef] [PubMed]
  117. Boué-Grabot, E.; Pankratov, Y. Modulation of Central Synapses by Astrocyte-Released ATP and Postsynaptic P2X Receptors. Neural Plast. 2017, 2017, 9454275. [Google Scholar] [CrossRef] [Green Version]
  118. Kovács, Z.; Skatchkov, S.N.; Veh, R.W.; Szabó, Z.; Németh, K.; Szabó, P.T.; Kardos, J.; Héja, L. Critical Role of Astrocytic Polyamine and GABA Metabolism in Epileptogenesis. Front. Cell. Neurosci. 2021, 15, 787319. [Google Scholar] [CrossRef]
  119. Lalo, U.; Pankratov, Y. ATP-mediated signalling in the central synapses. Neuropharmacology 2023, 229, 109477. [Google Scholar] [CrossRef]
  120. Rebola, N.; Lujan, R.; Cunha, R.A.; Mulle, C. Adenosine A2A receptors are essential for long-term potentiation of NMDA-EPSCs at hippocampal mossy fiber synapses. Neuron 2008, 57, 121–134. [Google Scholar] [CrossRef] [Green Version]
  121. Laming, P.R.; Kimelberg, H.; Robinson, S.; Salm, A.; Hawrylak, N.; Muller, C.; Roots, B.; Ng, K. Neuronal-glial interactions and behaviour. Neurosci. Biobehav. Rev. 2000, 24, 295–340. [Google Scholar] [CrossRef]
  122. Halassa, M.M.; Haydon, P.G. Integrated brain circuits: Astrocytic networks modulate neuronal activity and behavior. Annu. Rev. Physiol. 2010, 72, 335–355. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  123. Lalo, U.; Koh, W.; Lee, C.J.; Pankratov, Y. The tripartite glutamatergic synapse. Neuropharmacology 2021, 199, 108758. [Google Scholar] [CrossRef] [PubMed]
  124. Adamsky, A.; Kol, A.; Kreisel, T.; Doron, A.; Ozeri-Engelhard, N.; Melcer, T.; Refaeli, R.; Horn, H.; Regev, L.; Groysman, M.; et al. Astrocytic Activation Generates De Novo Neuronal Potentiation and Memory Enhancement. Cell 2018, 174, 59–71 e14. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  125. Stevens, E.R.; Esguerra, M.; Kim, P.M.; Newman, E.A.; Snyder, S.H.; Zahs, K.R.; Miller, R.F. D-serine and serine racemase are present in the vertebrate retina and contribute to the physiological activation of NMDA receptors. Proc. Natl. Acad. Sci. USA 2003, 100, 6789–6794. [Google Scholar] [CrossRef] [Green Version]
  126. Lalo, U.; Rasooli-Nejad, S.; Bogdanov, A.; More, L.; Koh, W.; Muller, J.; Wall, M.; Lee, C.J.; Pankratov, Y. Synergy between vesicular and non-vesicular gliotransmission regulates synaptic plasticity and working memory. BioRxiv 2021. [Google Scholar] [CrossRef]
  127. Benedikt, J.; Malpica-Nieves, C.J.; Rivera, Y.; Méndez-González, M.; Nichols, C.G.; Veh, R.W.; Eaton, M.J.; Skatchkov, S.N. The Polyamine Spermine Potentiates the Propagation of Negatively Charged Molecules through the Astrocytic Syncytium. Biomolecules 2022, 12, 1812. [Google Scholar] [CrossRef]
  128. Kiyoshi, C.M.; Du, Y.; Zhong, S.; Wang, W.; Taylor, A.T.; Xiong, B.; Ma, B.; Terman, D.; Zhou, M. Syncytial isopotentiality: A system-wide electrical feature of astrocytic networks in the brain. Glia 2018, 66, 2756–2769. [Google Scholar] [CrossRef]
  129. Kovács, Z.; Skatchkov, S.N.; Szabó, Z.; Qahtan, S.; Méndez-González, M.P.; Malpica-Nieves, C.J.; Eaton, M.J.; Kardos, J.; Héja, L. Putrescine Intensifies Glu/GABA Exchange Mechanism and Promotes Early Termination of Seizures. Int. J. Mol. Sci. 2022, 23, 8191. [Google Scholar] [CrossRef]
  130. Chiu, C.Q.; Barberis, A.; Higley, M.J. Preserving the balance: Diverse forms of long-term GABAergic synaptic plasticity. Nat. Rev. Neurosci. 2019, 20, 272–281. [Google Scholar] [CrossRef]
  131. Barberis, A. Postsynaptic plasticity of GABAergic synapses. Neuropharmacology 2020, 169, 107643. [Google Scholar] [CrossRef]
  132. Liu, G. Local structural balance and functional interaction of excitatory and inhibitory synapses in hippocampal dendrites. Nat. Neurosci. 2004, 7, 373–379. [Google Scholar] [CrossRef]
  133. Lagrange, A.H.; Hu, N.; Macdonald, R.L. GABA beyond the synapse: Defining the subtype-specific pharmacodynamics of non-synaptic GABA(A) receptors. J. Physiol. 2018, 596, 4475–4495. [Google Scholar] [CrossRef] [Green Version]
  134. Tyagarajan, S.K.; Fritschy, J.M. Gephyrin: A master regulator of neuronal function? Nat. Rev. Neurosci. 2014, 15, 141–156. [Google Scholar] [CrossRef] [Green Version]
  135. Choii, G.; Ko, J. Gephyrin: A central GABAergic synapse organizer. Exp. Mol. Med. 2015, 47, e158. [Google Scholar] [CrossRef] [Green Version]
  136. Petrini, E.M.; Ravasenga, T.; Hausrat, T.J.; Iurilli, G.; Olcese, U.; Racine, V.; Sibarita, J.B.; Jacob, T.C.; Moss, S.J.; Benfenati, F.; et al. Synaptic recruitment of gephyrin regulates surface GABAA receptor dynamics for the expression of inhibitory LTP. Nat. Commun. 2014, 5, 3921. [Google Scholar] [CrossRef] [Green Version]
  137. Ostrovskaya, O.; Xie, K.; Masuho, I.; Fajardo-Serrano, A.; Lujan, R.; Wickman, K.; Martemyanov, K.A. RGS7/Gβ5/R7BP complex regulates synaptic plasticity and memory by modulating hippocampal GABABR-GIRK signaling. Elife 2014, 3, e02053. [Google Scholar] [CrossRef] [PubMed]
  138. Booker, S.A.; Loreth, D.; Gee, A.L.; Watanabe, M.; Kind, P.C.; Wyllie, D.J.A.; Kulik, Á.; Vida, I. Postsynaptic GABA(B)Rs Inhibit L-Type Calcium Channels and Abolish Long-Term Potentiation in Hippocampal Somatostatin Interneurons. Cell. Rep. 2018, 22, 36–43. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  139. Xu, C.; Zhao, M.X.; Poo, M.M.; Zhang, X.H. GABA(B) receptor activation mediates frequency-dependent plasticity of developing GABAergic synapses. Nat. Neurosci. 2008, 11, 1410–1418. [Google Scholar] [CrossRef] [PubMed]
  140. Tosetti, P.; Ferrand, N.; Colin-Le Brun, I.; Gaïarsa, J.L. Epileptiform activity triggers long-term plasticity of GABA(B) receptor signalling in the developing rat hippocampus. J. Physiol. 2005, 568, 951–966. [Google Scholar] [CrossRef]
  141. Butt, S.J.; Stacey, J.A.; Teramoto, Y.; Vagnoni, C. A role for GABAergic interneuron diversity in circuit development and plasticity of the neonatal cerebral cortex. Curr. Opin. Neurobiol. 2017, 43, 149–155. [Google Scholar] [CrossRef]
  142. Wang, L.; Maffei, A. Inhibitory plasticity dictates the sign of plasticity at excitatory synapses. J. Neurosci. 2014, 34, 1083–1093. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  143. Neveu, D.; Zucker, R.S. Postsynaptic levels of [Ca2+] i needed to trigger LTD and LTP. Neuron 1996, 16, 619–629. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  144. Ellis-Davies, G.C. Two-photon microscopy for chemical neuroscience. ACS Chem. Neurosci. 2011, 2, 185–197. [Google Scholar] [CrossRef] [PubMed]
  145. Pettit, D.L.; Augustine, G.J. Chemical two-photon uncaging. CSH Protoc. 2007, 2007. [Google Scholar] [CrossRef] [PubMed]
  146. Noguchi, J.; Nagaoka, A.; Watanabe, S.; Ellis-Davies, G.C.; Kitamura, K.; Kano, M.; Matsuzaki, M.; Kasai, H. In vivo two-photon uncaging of glutamate revealing the structure–function relationships of dendritic spines in the neocortex of adult mice. J. Physiol. 2011, 589, 2447–2457. [Google Scholar] [CrossRef] [PubMed]
  147. Kruijssen, D.L.H.; Wierenga, C.J. Single Synapse LTP: A Matter of Context? Front. Cell. Neurosci. 2019, 13, 496. [Google Scholar] [CrossRef] [Green Version]
  148. Noguchi, J.; Nagaoka, A.; Hayama, T.; Ucar, H.; Yagishita, S.; Takahashi, N.; Kasai, H. Bidirectional in vivo structural dendritic spine plasticity revealed by two-photon glutamate uncaging in the mouse neocortex. Sci. Rep. 2019, 9, 13922. [Google Scholar] [CrossRef] [Green Version]
  149. Denk, W.; Svoboda, K. Photon upmanship: Why multiphoton imaging is more than a gimmick. Neuron 1997, 18, 351–357. [Google Scholar] [CrossRef] [Green Version]
  150. Helmchen, F.; Denk, W. Deep tissue two-photon microscopy. Nat. Methods 2005, 2, 932–940. [Google Scholar] [CrossRef]
  151. Wilt, B.A.; Burns, L.D.; Wei Ho, E.T.; Ghosh, K.K.; Mukamel, E.A.; Schnitzer, M.J. Advances in light microscopy for neuroscience. Annu. Rev. Neurosci. 2009, 32, 435–506. [Google Scholar] [CrossRef] [Green Version]
  152. Schreurs, A.; Leenders, N.; Sabanov, V.; Van Den Haute, C.; Welkenhuysen, M.; Hoffman, L.; Braeken, D.; Baekelandt, V.; Balschun, D. Optogenetic Inhibition of Long-Term Potentiation in the Mouse Dentate Gyrus. In Proceedings of the Abstract: 12th National Congress of the Belgian Society for Neuroscience, Gent, Belgium, 22 May 2017. [Google Scholar]
  153. Quinlan, M.A.; Strong, V.M.; Skinner, D.M.; Martin, G.M.; Harley, C.W.; Walling, S.G. Locus coeruleus optogenetic light activation induces long-term potentiation of perforant path population spike amplitude in rat dentate gyrus. Front. Syst. Neurosci. 2019, 12, 67. [Google Scholar] [CrossRef]
  154. Rost, B.R.; Wietek, J.; Yizhar, O.; Schmitz, D. Optogenetics at the presynapse. Nat. Neurosci. 2022, 25, 984–998. [Google Scholar] [CrossRef] [PubMed]
  155. Asgarihafshejani, A.; Honoré, È.; Michon, F.X.; Laplante, I.; Lacaille, J.C. Long-term potentiation at pyramidal cell to somatostatin interneuron synapses controls hippocampal network plasticity and memory. iScience 2022, 25, 104259. [Google Scholar] [CrossRef] [PubMed]
  156. Udakis, M.; Pedrosa, V.; Chamberlain, S.E.L.; Clopath, C.; Mellor, J.R. Interneuron-specific plasticity at parvalbumin and somatostatin inhibitory synapses onto CA1 pyramidal neurons shapes hippocampal output. Nat. Commun. 2020, 11, 4395. [Google Scholar] [CrossRef]
  157. Froemke, R.C. Plasticity of cortical excitatory-inhibitory balance. Annu. Rev. Neurosci. 2015, 38, 195–219. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  158. Hennequin, G.; Agnes, E.J.; Vogels, T.P. Inhibitory Plasticity: Balance, Control, and Codependence. Annu. Rev. Neurosci. 2017, 40, 557–579. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  159. Paulsen, O.; Sejnowski, T.J. Natural patterns of activity and long-term synaptic plasticity. Curr. Opin. Neurobiol. 2000, 10, 172–180. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  160. Monier, C.; Fournier, J.; Frégnac, Y. In vitro and in vivo measures of evoked excitatory and inhibitory conductance dynamics in sensory cortices. J. Neurosci. Methods 2008, 169, 323–365. [Google Scholar] [CrossRef]
  161. Willems, J.G.P.; Wadman, W.J.; Cappaert, N.L.M. Interaction of Cortical and Amygdalar Synaptic Input Modulates the Window of Opportunity for Information Processing in the Rhinal Cortices. eNeuro 2019, 6. [Google Scholar] [CrossRef]
  162. Angelo, K.; Margrie, T.W. Population diversity and function of hyperpolarization-activated current in olfactory bulb mitral cells. Sci. Rep. 2011, 1, 50. [Google Scholar] [CrossRef] [Green Version]
  163. Bear, M.F.; Malenka, R.C. Synaptic plasticity: LTP and LTD. Curr. Opin. Neurobiol. 1994, 4, 389–399. [Google Scholar] [CrossRef] [PubMed]
  164. Heynen, A.J.; Abraham, W.C.; Bear, M.F. Bidirectional modification of CA1 synapses in the adult hippocampus in vivo. Nature 1996, 381, 163–166. [Google Scholar] [CrossRef] [PubMed]
  165. Suppa, A.; Marsili, L.; Belvisi, D.; Conte, A.; Iezzi, E.; Modugno, N.; Fabbrini, G.; Berardelli, A. Lack of LTP-like plasticity in primary motor cortex in Parkinson’s disease. Exp. Neurol. 2011, 227, 296–301. [Google Scholar] [CrossRef] [PubMed]
  166. Li, X.H.; Matsuura, T.; Xue, M.; Chen, Q.Y.; Liu, R.H.; Lu, J.S.; Shi, W.; Fan, K.; Zhou, Z.; Miao, Z.; et al. Oxytocin in the anterior cingulate cortex attenuates neuropathic pain and emotional anxiety by inhibiting presynaptic long-term potentiation. Cell Rep. 2021, 36, 109411. [Google Scholar] [CrossRef]
  167. Shankar, G.M.; Li, S.; Mehta, T.H.; Garcia-Munoz, A.; Shepardson, N.E.; Smith, I.; Brett, F.M.; Farrell, M.A.; Rowan, M.J.; Lemere, C.A.; et al. Amyloid-beta protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nat. Med. 2008, 14, 837–842. [Google Scholar] [CrossRef] [Green Version]
  168. Di Lorenzo, F.; Motta, C.; Bonnì, S.; Mercuri, N.B.; Caltagirone, C.; Martorana, A.; Koch, G. LTP-like cortical plasticity is associated with verbal memory impairment in Alzheimer’s disease patients. Brain Stimul. 2019, 12, 148–151. [Google Scholar] [CrossRef]
  169. Bialas, M.; Mandziuk, J. Spike-Timing-Dependent Plasticity With Activation-Dependent Scaling for Receptive Fields Development. IEEE Trans. Neural Netw. Learn. Syst. 2022, 33, 5215–5228. [Google Scholar] [CrossRef]
  170. Cutsuridis, V. GABA inhibition modulates NMDA-R mediated spike timing dependent plasticity (STDP) in a biophysical model. Neural Netw. 2011, 24, 29–42. [Google Scholar] [CrossRef]
  171. Inglebert, Y.; Debanne, D. Calcium and Spike Timing-Dependent Plasticity. Front. Cell Neurosci. 2021, 15, 727336. [Google Scholar] [CrossRef]
  172. Wang, Y.; Fu, W.Y.; Cheung, K.; Hung, K.W.; Chen, C.; Geng, H.; Yung, W.H.; Qu, J.Y.; Fu, A.K.Y.; Ip, N.Y. Astrocyte-secreted IL-33 mediates homeostatic synaptic plasticity in the adult hippocampus. Proc. Natl. Acad. Sci. USA 2021, 118, e2020810118. [Google Scholar] [CrossRef]
  173. Shin, R.M.; Tully, K.; Li, Y.; Cho, J.H.; Higuchi, M.; Suhara, T.; Bolshakov, V.Y. Hierarchical order of coexisting pre- and postsynaptic forms of long-term potentiation at synapses in amygdala. Proc. Natl. Acad. Sci. USA 2010, 107, 19073–19078. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  174. Shrivastava, K.; Schayek, R.; Kritman, M.; Maroun, M. Differential Age-dependent Mechanisms of High-frequency Stimulation-induced Potentiation in the Prefrontal Cortex-Basolateral Amygdala Pathway Following Fear Extinction. Neuroscience 2022, 491, 215–224. [Google Scholar] [CrossRef] [PubMed]
  175. Mendoza, M.L.; Quigley, L.D.; Dunham, T.; Volk, L.J. KIBRA regulates activity-induced AMPA receptor expression and synaptic plasticity in an age-dependent manner. iScience 2022, 25, 105623. [Google Scholar] [CrossRef] [PubMed]
  176. Wong, L.W.; Chong, Y.S.; Lin, W.; Kisiswa, L.; Sim, E.; Ibáñez, C.F.; Sajikumar, S. Age-related changes in hippocampal-dependent synaptic plasticity and memory mediated by p75 neurotrophin receptor. Aging Cell. 2021, 20, e13305. [Google Scholar] [CrossRef] [PubMed]
  177. Lewis, S. Interspecies differences. Nat. Rev. Neurosci. 2022, 23, 69. [Google Scholar] [CrossRef]
  178. Olsen, M.L.; Khakh, B.S.; Skatchkov, S.N.; Zhou, M.; Lee, C.J.; Rouach, N. New insights on astrocyte ion channels: Critical for homeostasis and neuron-glia signaling. J. Neurosci. 2015, 35, 13827–13835. [Google Scholar] [CrossRef] [Green Version]
  179. Lioy, D.T.; Garg, S.K.; Monaghan, C.E.; Raber, J.; Foust, K.D.; Kaspar, B.K.; Hirrlinger, P.G.; Kirchhoff, F.; Bissonnette, J.M.; Ballas, N.; et al. A role for glia in the progression of Rett’s syndrome. Nature 2011, 475, 497–500. [Google Scholar] [CrossRef] [Green Version]
  180. Tong, X.; Ao, Y.; Faas, G.C.; Nwaobi, S.E.; Xu, J.; Haustein, M.D.; Anderson, M.A.; Mody, I.; Olsen, M.L.; Sofroniew, M.V.; et al. Astrocyte Kir4.1 ion channel deficits contribute to neuronal dysfunction in Huntington’s disease model mice. Nat. Neurosci. 2014, 17, 694–703. [Google Scholar] [CrossRef] [Green Version]
  181. Jo, S.; Yarishkin, O.; Hwang, Y.J.; Chun, Y.E.; Park, M.; Woo, D.H.; Bae, J.Y.; Kim, T.; Lee, J.; Chun, H.; et al. GABA from reactive astrocytes impairs memory in mouse models of Alzheimer’s disease. Nat. Med. 2014, 20, 886–896. [Google Scholar] [CrossRef]
Figure 1. Three types of electrophysiological recordings in long-term potentiation (LTP). (A): In vivo optogenetics recordings. (B): In vitro electrode array recording. (C): In vitro whole-cell patch-clamp recordings. (D,E): Traces and normalized slope of excitatory postsynaptic potential or inhibitory postsynaptic current EPSC/IPSC before and after stimulation.
Figure 1. Three types of electrophysiological recordings in long-term potentiation (LTP). (A): In vivo optogenetics recordings. (B): In vitro electrode array recording. (C): In vitro whole-cell patch-clamp recordings. (D,E): Traces and normalized slope of excitatory postsynaptic potential or inhibitory postsynaptic current EPSC/IPSC before and after stimulation.
Ijms 24 07134 g001
Figure 2. Mechanism of iLTP and the underlying mechanism of astrocyte regulation of iLTP. The red, green, and purple pathways represent the mechanism of NO-mediated long-term potentiation, BDNF-TrkB_iLTP, and NMDAR-dependent _iLTP, respectively. Astrocytes release ATP and D-serine by increasing intracellular calcium ions, which is necessary for NMDA-dependent LTP. Polyamine putrescine (PUT) is an important source of astrocyte GABA production. Significant GABA release suggests that the astrocyte Glu-GABA exchange mechanism is the key to limiting ictal discharge. This evidence may show a new mechanism for regulating iLTP.
Figure 2. Mechanism of iLTP and the underlying mechanism of astrocyte regulation of iLTP. The red, green, and purple pathways represent the mechanism of NO-mediated long-term potentiation, BDNF-TrkB_iLTP, and NMDAR-dependent _iLTP, respectively. Astrocytes release ATP and D-serine by increasing intracellular calcium ions, which is necessary for NMDA-dependent LTP. Polyamine putrescine (PUT) is an important source of astrocyte GABA production. Significant GABA release suggests that the astrocyte Glu-GABA exchange mechanism is the key to limiting ictal discharge. This evidence may show a new mechanism for regulating iLTP.
Ijms 24 07134 g002
Figure 3. Coordinated plasticity of excitatory and inhibitory synapses [55]. LTP induction at a single glutamatergic spine leads to inhibition of nearby GABAergic inhibitory synapses (<3 μm, iLTD), while more distant synapses are enhanced (>3 μm, iLTP), and such GABA_iLTP is heterosynaptic.
Figure 3. Coordinated plasticity of excitatory and inhibitory synapses [55]. LTP induction at a single glutamatergic spine leads to inhibition of nearby GABAergic inhibitory synapses (<3 μm, iLTD), while more distant synapses are enhanced (>3 μm, iLTP), and such GABA_iLTP is heterosynaptic.
Ijms 24 07134 g003
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Jiang, F.; Bello, S.T.; Gao, Q.; Lai, Y.; Li, X.; He, L. Advances in the Electrophysiological Recordings of Long-Term Potentiation. Int. J. Mol. Sci. 2023, 24, 7134. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24087134

AMA Style

Jiang F, Bello ST, Gao Q, Lai Y, Li X, He L. Advances in the Electrophysiological Recordings of Long-Term Potentiation. International Journal of Molecular Sciences. 2023; 24(8):7134. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24087134

Chicago/Turabian Style

Jiang, Feixu, Stephen Temitayo Bello, Qianqian Gao, Yuanying Lai, Xiao Li, and Ling He. 2023. "Advances in the Electrophysiological Recordings of Long-Term Potentiation" International Journal of Molecular Sciences 24, no. 8: 7134. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24087134

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop