Synaptic Long-term Potentiation Research Articles

Hebbian plasticity: the elusive missing link at the heart of Alzheimer's disease pathogenesis?

Hebbian plasticity: the elusive missing link at the heart of Alzheimer's disease pathogenesis?

PINK1-mediated Drp1S616 phosphorylation modulates synaptic development and plasticity via promoting mitochondrial fission

Dynamic change of mitochondrial morphology and distribution along neuronal branches are essential for neural circuitry formation and synaptic efficacy. However, the underlying mechanism remains elusive. We show here that Pink1 knockout (KO) mice display defective dendritic spine maturation, reduced axonal synaptic vesicles, abnormal synaptic connection, and attenuated long-term synaptic potentiation (LTP). Drp1 activation via S616 phosphorylation rescues deficits of spine maturation in Pink1 KO neurons. Notably, mice harboring a knockin (KI) phosphor-null Drp1S616A recapitulate spine immaturity and synaptic abnormality identified in Pink1 KO mice. Chemical LTP (cLTP) induces Drp1S616 phosphorylation in a PINK1-dependent manner. Moreover, phosphor-mimetic Drp1S616D restores reduced dendritic spine localization of mitochondria in Pink1 KO neurons. Together, this study provides the first in vivo evidence of functional regulation of Drp1 by phosphorylation and suggests that PINK1-Drp1S616 phosphorylation coupling is essential for convergence between mitochondrial dynamics and neural circuitry formation and refinement.

Recovery of Angelman syndrome rat deficits with UBE3A protein supplementation

We recently generated a novel Angelman syndrome (AS) rat model with a complete Ube3a gene deletion, that recapitulates the loss of UBE3A protein and shows cognitive and EEG deficits. We also recently published the identification of extracellular UBE3A protein within the brain using microdialysis. Here we explored the effects of supplementation of exogenous UBE3A protein to hippocampal slices and intrahippocampal injection of AS rats. We report that the AS rat model demonstrates deficits in hippocampal long-term potentiation (LTP) which can be recovered with the application of exogenous UBE3A protein. Furthermore, injection of recombinant UBE3A protein into the hippocampus of the AS rat can rescue the associative learning and memory deficits seen in the fear conditioning task. These data suggest that extracellular UBE3A protein may play a role in synaptic function, LTP induction and hippocampal-dependent memory formation.

Matrix Metalloproteinase-9 as an Important Contributor to the Pathophysiology of Depression.

Matrix metalloproteinases (MMPs) are physiologically expressed in the central nervous system in neurons, astrocytes and microglia, and their aberrant elevation contributes to a number of diseases. Amongst the MMP members, MMP−9 has generated considerable attention because of its possible involvement in inflammatory responses, blood-brain barrier permeability, the regulation of perineuronal nets, demyelination, and synaptic long-term potentiation. Emerging evidence indicate an association between MMP−9 and the syndrome of depression. This review provides an updated and comprehensive summary of the probable roles of MMP−9 in depression with an emphasis on the mechanisms and potential of MMP−9 as a biomarker of depression.

Aberrant hippocampal transmission and behavior in mice with a stargazin mutation linked to intellectual disability

Mutations linked to neurodevelopmental disorders, such as intellectual disability (ID), are frequently found in genes that encode for proteins of the excitatory synapse. Transmembrane AMPA receptor regulatory proteins (TARPs) are AMPA receptor auxiliary proteins that regulate crucial aspects of receptor function. Here, we investigate a mutant form of the TARP family member stargazin, described in an ID patient. Molecular dynamics analyses predicted that the ID-associated stargazin variant, V143L, weakens the overall interface of the AMPAR:stargazin complex and impairs the stability of the complex. Knock-in mice harboring the V143L stargazin mutation manifest cognitive and social deficits and hippocampal synaptic transmission defects, resembling phenotypes displayed by ID patients. In the hippocampus of stargazin V143L mice, CA1 neurons show impaired spine maturation, abnormal synaptic transmission and long-term potentiation specifically in basal dendrites, and synaptic ultrastructural alterations. These data suggest a causal role for mutated stargazin in the pathogenesis of ID and unveil a new role for stargazin in the development and function of hippocampal synapses.

Advanced maternal age impairs synaptic plasticity in offspring rats

Advanced maternal age (AMA) has become more common in the last decade and is associated with poor neurodevelopmental outcomes in offspring. Neurocognitive and emotional development is associated with synaptic structural and functional plasticity. In the present study, we investigated the relationship between AMA and synapse plasticity in the offspring. We examined the synaptic ultrastructure, synapse-related proteins and long-term potentiation (LTP) in the offspring of Sprague–Dawley female rats aged 12 months (AMA group) and 3 months (Control group) on postnatal (P) days 7, 14, 28 and 60. Immunofluorescence analysis revealed decreases in the expression of neurofilament 200 (NF200) and axon length in the AMA group compared with the control group at P14. Western blot analysis showed that the expression of postsynaptic density-95 (PSD-95) and synaptophysin (SYP) was reduced in the immature offspring of the AMA group at P7. Transmission electron microscopy showed decreased thickness of the PSD and increased length of the active zone (AZ) in the offspring of the AMA group. Electrophysiological recordings in hippocampal slices revealed impaired LTP in the AMA offspring. Our data suggest that AMA impairs the synaptic plasticity of offspring, which may underlie the mechanism of neurodevelopmental disorders.

Activity-dependent PI4P synthesis by PI4KIIIα regulates long-term synaptic potentiation

Phosphatidylinositol 4-phosphate (PI4P) is a low abundant phospholipid with important roles in lipid transport and membrane trafficking. However, little is known of its metabolism and function in neurons. Here, we investigate its subcellular distribution and functional roles in dendrites of rodent hippocampal neurons during resting state and long-term synaptic potentiation (LTP). We show that neural activity causes dynamic reversible changes in PI4P metabolism in dendrites. Upon LTP induction, PI4KIIIα, a type III phosphatidylinositol 4-kinase, localizes to the dendritic plasma membrane (PM) in a calcium-dependent manner and causes substantial increase in the levels of PI4P. Acute inhibition of PI4KIIIα activity abolishes trafficking of the AMPA-type glutamate receptor to the PM during LTP induction, and silencing of PI4KIIIα expression in the hippocampal CA1 region causes severe impairment of LTP and long-term memory. Collectively, our results identify an essential role for PI4KIIIα-dependent PI4P synthesis in synaptic plasticity of central nervous system neurons.

Pharmacological inhibition of STriatal-Enriched protein tyrosine Phosphatase by TC-2153 reduces hippocampal excitability and seizure propensity.

STriatal-Enriched protein tyrosine Phosphatase (STEP) is a brain-specific tyrosine phosphatase. Membrane-bound STEP61 is the only isoform expressed in hippocampus and cortex. Genetic deletion of STEP enhances excitatory synaptic currents and long-term potentiation in the hippocampus. However, whether STEP61 affects seizure susceptibility is unclear. Here we investigated the effects of STEP inhibitor TC-2153 on seizure propensity in a murine model displaying kainic acid (KA)-induced status epilepticus and its effect on hippocampal excitability. Adult male and female C57BL/6J mice received intraperitoneal injection of either vehicle (2.8% dimethylsulfoxide [DMSO] in saline) or TC-2153 (10mg/kg) and then either saline or KA (30mg/kg) 3h later before being monitored for behavioral seizures. A subset of female mice was ovariectomized (OVX). Acute hippocampal slices from Thy1-GCaMP6s mice were treated with either DMSO or TC-2153 (10μM) for 1h, and then incubated in artificial cerebrospinal fluid (ACSF) and potassium chloride (15mM) for 2min prior to live calcium imaging. Pyramidal neurons in dissociated rat hippocampal culture (DIV 8-10) were pre-treated with DMSO or TC-2153 (10µM) for 1h before whole-cell patch-clamp recording. TC-2153 treatment significantly reduced KA-induced seizure severity, with greater trend seen in female mice. OVX abolished this TC-2153-induced decrease in seizure severity in female mice. TC-2153 application significantly decreased overall excitability of acute hippocampal slices from both sexes. Surprisingly, TC-2153 treatment hyperpolarized resting membrane potential and decreased firing rate, sag voltage, and hyperpolarization-induced current (Ih ) of cultured hippocampal pyramidal neurons. This study is the first to demonstrate that pharmacological inhibition of STEP with TC-2153 decreases seizure severity and hippocampal activity in both sexes, and dampens hippocampal neuronal excitability and Ih . We propose that the antiseizure effects of TC-2153 are mediated by its unexpected action on suppressing neuronal intrinsic excitability.

Brain-derived neurotrophic factor-induced regulation of RNA metabolism in neuronal development and synaptic plasticity.

The neurotrophin brain-derived neurotrophic factor (BDNF) plays multiple roles in the nervous system, including in neuronal development, in long-term synaptic potentiation in different brain regions, and in neuronal survival. Alterations in these regulatory mechanisms account for several diseases of the nervous system. The synaptic effects of BDNF mediated by activation of tropomyosin receptor kinase B (TrkB) receptors are partly mediated by stimulation of local protein synthesis which is now considered a ubiquitous feature in both presynaptic and postsynaptic compartments of the neuron. The capacity to locally synthesize proteins is of great relevance at several neuronal developmental stages, including during neurite development, synapse formation, and stabilization. The available evidence shows that the effects of BDNF-TrkB signaling on local protein synthesis regulate the structure and function of the developing and mature synapses. While a large number of studies have illustrated a wide range of effects of BDNF on the postsynaptic proteome, a growing number of studies also point to presynaptic effects of the neurotrophin in the local regulation of the protein composition at the presynaptic level. Here, we will review the latest evidence on the role of BDNF in local protein synthesis, comparing the effects on the presynaptic and postsynaptic compartments. Additionally, we overview the relevance of BDNF-associated local protein synthesis in neuronal development and synaptic plasticity, at the presynaptic and postsynaptic compartments, and their relevance in terms of disease. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA Export and Localization > RNA Localization.

Acid-Sensing Ion Channels in Glial Cells.

Acid-sensing ion channels (ASICs) are proton-gated cation channels and key mediators of responses to neuronal injury. ASICs exhibit unique patterns of distribution in the brain, with high expression in neurons and low expression in glial cells. While there has been a lot of focus on ASIC in neurons, less is known about the roles of ASICs in glial cells. ASIC1a is expressed in astrocytes and might contribute to synaptic transmission and long-term potentiation. In oligodendrocytes, constitutive activation of ASIC1a participates in demyelinating diseases. ASIC1a, ASIC2a, and ASIC3, found in microglial cells, could mediate the inflammatory response. Under pathological conditions, ASIC dysregulation in glial cells can contribute to disease states. For example, activation of astrocytic ASIC1a may worsen neurodegeneration and glioma staging, activation of microglial ASIC1a and ASIC2a may perpetuate ischemia and inflammation, while oligodendrocytic ASIC1a might be involved in multiple sclerosis. This review concentrates on the unique ASIC components in each of the glial cells and integrates these glial-specific ASICs with their physiological and pathological conditions. Such knowledge provides promising evidence for targeting of ASICs in individual glial cells as a therapeutic strategy for a diverse range of conditions.

Adiponectin Ameliorates Cognitive Behaviors and in vivo Synaptic Plasticity Impairments in 3xTg-AD Mice.

Cognitive deficit is mainly clinical characteristic of Alzheimer's disease (AD). Recent reports showed adiponectin and its analogues could reverse cognitive impairments, lower amyloid-β protein (Aβ) deposition, and exert anti-inflammatory effects in different APP/PS1 AD model mice mainly exhibiting amyloid plaque pathology. However, the potential in vivo electrophysiological mechanism of adiponectin protecting against cognitive deficits in AD and the neuroprotective effects of adiponectin on 3xTg-AD mice including both plaque and tangle pathology are still unclear. To observe the effects of adiponectin treatment on cognitive deficits in 3xTg-AD mice, investigate its potential in vivo electrophysiological mechanism, and testify its anti-inflammatory effects. Barnes maze test, Morris water maze test, and fear conditioning test were used to evaluate the memory-ameliorating effects of adiponectin on 3xTg-AD mice. In vivo hippocampal electrophysiological recording was used to observe the change of basic synaptic transmission, long-term potentiation, and long-term depression. Immunohistochemistry staining and western blot were used to observe the activation of microglia and astroglia, and the expression levels of proinflammatory factors and anti-inflammtory factor IL-10. Adiponectin treatment could alleviate spatial memory and conditioned fear memory deficits observed in 3xTg-AD mice, improve in vivo LTP depression and LTD facilitation, inhibit overactivation of microglia and astroglia, decrease the expression of proinflammatory factors NF- κB and IL-1β, and increase the expression level of IL-10 in the hippocampus of 3xTg-AD mice. Adiponectin could ameliorate cognitive deficits in 3xTg-AD mice through improving in vivo synaptic plasticity impairments and alleviating neuroinflammation in the hippocampus of 3xTg-AD mice.

Late-Onset Behavioral and Synaptic Consequences of L-Type Ca2+ Channel Activation in the Basolateral Amygdala of Developing Rats.

Postnatal CNS development is fine-tuned to drive the functional needs of succeeding life stages; accordingly, the emergence of sensory and motor functions, behavioral patterns and cognitive abilities relies on a complex interplay of signaling pathways. Strictly regulated Ca2+ signaling mediated by L-type channels (LTCCs) is crucial in neural circuit development and aberrant increases in neuronal LTCC activity are linked to neurodevelopmental and psychiatric disorders. In the amygdala, a brain region that integrates signals associated with aversive and rewarding stimuli, LTCCs contribute to NMDA-independent long-term potentiation (LTP) and are required for the consolidation and extinction of fear memory. In vitro studies have elucidated distinct electrophysiological and synaptic properties characterizing the transition from immature to functionally mature basolateral subdivision of the amygdala (BLA) principal neurons. Further, acute increase of LTCC activity selectively regulates excitability and spontaneous synaptic activity in immature BLA neurons, suggesting an age-dependent regulation of BLA circuitry by LTCCs. This study aimed to elucidate whether early life alterations in LTCC activity subsequently affect synaptic strength and amygdala-dependent behaviors in early adulthood. In vivo intra-amygdala injection of an LTCC agonist at a critical period of postnatal neurodevelopment in male rat pups was used to examine synaptic plasticity of BLA excitatory inputs, expression of immediate early genes (IEGs) and glutamate receptors, as well as anxiety and social affiliation behaviors at a juvenile age. Results indicate that enhanced LTCC activity in immature BLA principal neurons trigger persistent changes in the developmental trajectory to modify membrane properties and synaptic LTP at later stages, concomitant with alterations in amygdala-related behavioral patterns.

Emulating Switching From Short-Term to Long-Term Plasticity of Bio-Synapse Using Split Gate MOSFET

For the development of brain-inspired neuromorphic hardware with high integration density and connectivity in this work, we have proposed a fully planar, CMOS compatible, and energy efficient (inference energy &#x003D; 7.4x10^-17 J) tunable-split gate synaptic transistor (T-SGST) with correlation-based plasticity. Valence band offset (VBO) in the device due to SiGe region and charge trapping&#x002F;de-trapping in the nitride layer are found to be effective for synaptic learning (short-term potentiation (STP), long-term potentiation (LTP), and long-term depression (LTD)) at low trapping&#x002F;de-trapping voltage (<inline-formula><tex-math notation="LaTeX">${V}_{G2S} = | {3.5} |V$</tex-math></inline-formula>). Furthermore, the switching from STP to LTP is governed by repeated input pulses (correlation-based plasticity) and the bias potential on gate 1 (G1). The proposed T-SGST offers a switching at the 8^th input pulse when G1 is tuned at <i>V_G</i>₁<i>_S</i> &#x003D; 0 V, whereas for <i>V_G</i>₁<i>_S</i> &#x003D; -0.2 V there is no switching. In addition, we have also reported the strong dependence of the interval time between input pulses on switching. These findings in our proposed T-SGST device make it a promising candidate for application in the neuromorphic technology.

Heterogeneity of intrinsic plasticity in cerebellar Purkinje cells linked with cortical molecular zones

SummaryIn the cerebellar cortex, heterogeneous populations of Purkinje cells (PCs), classified into zebrin (aldolase C)-positive (Z+) and -negative (Z-) types, are arranged into separate longitudinal zones. They have different topographic neuronal connections and show different patterns of activity in behavior tasks. However, whether the zebrin type of PCs directly links with the physiological properties of the PC has not been well clarified. Therefore, we applied in vitro whole-cell patch-clamp recording in Z+ and Z- PCs in vermal and hemispheric neighboring zebrin zones in zebrin-visualized mice. Intrinsic excitability is significantly higher in Z- PCs than in Z+ PCs. Furthermore, intrinsic plasticity and synaptic long-term potentiation are enhanced more in Z- PCs than in Z+ PCs. The difference was mediated by different modulation of SK channel activities between Z+ and Z- PCs. The results indicate that cellular physiology differentially tunes to the functional compartmentalization of heterogeneous PCs.

Neuron-Derived Estrogen-A Key Neuromodulator in Synaptic Function and Memory.

In addition to being a steroid hormone, 17β-estradiol (E2) is also a neurosteroid produced in neurons in various regions of the brain of many species, including humans. Neuron-derived E2 (NDE2) is synthesized from androgen precursors via the action of the biosynthetic enzyme aromatase, which is located at synapses and in presynaptic terminals in neurons in both the male and female brain. In this review, we discuss evidence supporting a key role for NDE2 as a neuromodulator that regulates synaptic plasticity and memory. Evidence supporting an important neuromodulatory role of NDE2 in the brain has come from studies using aromatase inhibitors, aromatase overexpression in neurons, global aromatase knockout mice, and the recent development of conditional forebrain neuron-specific knockout mice. Collectively, these studies demonstrate a key role of NDE2 in the regulation of synapse and spine density, efficacy of excitatory synaptic transmission and long-term potentiation, and regulation of hippocampal-dependent recognition memory, spatial reference memory, and contextual fear memory. NDE2 is suggested to achieve these effects through estrogen receptor-mediated regulation of rapid kinase signaling and CREB-BDNF signaling pathways, which regulate actin remodeling, as well as transcription, translation, and transport of synaptic proteins critical for synaptic plasticity and function.

D1/D5 Dopamine Receptors and mGluR5 Jointly Enable Non-Hebbian Long-Term Potentiation at Sensory Synapses onto Lamina I Spinoparabrachial Neurons

Highly correlated firing of primary afferent inputs and lamina I projection neurons evokes synaptic long-term potentiation (LTP), a mechanism by which ascending nociceptive transmission can be amplified at the level of the spinal dorsal horn. However, the degree to which neuromodulatory signaling shapes the temporal window governing spike-timing-dependent plasticity (STDP) at sensory synapses onto projection neurons remains unclear. The present study demonstrates that activation of spinal D1/D5 dopamine receptors (D1/D5Rs) creates a highly permissive environment for the production of LTP in male and female adult mouse spinoparabrachial neurons by promoting non-Hebbian plasticity. Bath application of the mixed D1/D5R agonist SKF82958 unmasked LTP at STDP pairing intervals that normally fail to alter synaptic efficacy. Furthermore, during D1/D5R signaling, action potential discharge in projection neurons became dispensable for LTP generation, and primary afferent stimulation alone was sufficient to induce strengthening of sensory synapses. This non-Hebbian LTP was blocked by the D1/D5R antagonist SCH 39166 or genetic deletion of D5R, and required activation of mGluR5 and intracellular Ca2+ release but was independent of NMDAR activation. D1/D5R-enabled non-Hebbian plasticity was observed across multiple neuronal subpopulations in the superficial dorsal horn but was more prevalent in spinoparabrachial neurons than interneurons. Interestingly, the ability of neonatal tissue damage to promote non-Hebbian LTP in adult projection neurons was not observed in D5R knock-out mice. Collectively, these findings suggest that joint spinal D1/D5R and mGluR5 activation can allow unfettered potentiation of sensory synapses onto the output neurons responsible for conveying pain and itch information to the brain.SIGNIFICANCE STATEMENT Synaptic LTP in spinal projection neurons has been implicated in the generation of chronic pain. Under normal conditions, plasticity at sensory synapses onto adult mouse spinoparabrachial neurons follows strict Hebbian learning rules, requiring coincident presynaptic and postsynaptic firing. Here, we demonstrate that the activation of spinal D1/D5Rs promotes a switch from Hebbian to non-Hebbian LTP so that primary afferent stimulation alone is sufficient to evoke LTP in the absence of action potential discharge in projection neurons, which required joint activation of mGluR5 and intracellular Ca2+ release but not NMDARs. These results suggest that D1/D5Rs cooperate with mGluR5 receptors in the spinal dorsal horn to powerfully influence the amplification of ascending nociceptive transmission to the brain.

Alterations in amperometric cholinergic signals accompanied by synaptic plasticity and γ oscillations in the hippocampus-medial prefrontal cortex pathway.

Neural projections from the ventral hippocampal CA1 (vCA1) to the medial prefrontal cortex (mPFC) and from the posterior dorsal hippocampal CA1 (pdCA1) to the mPFC are important for information processing. Previous studies have revealed that two forms of long-term synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD), and γ oscillations, which are all believed to be neural bases for learning and memory in the vCA1-mPFC and the pdCA1-mPFC pathways, exhibited distinct profiles. However, the underlying mechanism is unclear. In the present study, amperometric cholinergic signals were monitored during in-vivo electrophysiological recordings of evoked extracellular postsynaptic potentials and spontaneous local field potentials. The results demonstrated that in the vCA1-mPFC pathway, increased cholinergic currents and γ power of the amperometric cholinergic signals were accompanied by the induction of LTD and increased γ power of local field potentials, whereas, in the pdCA1-mPFC pathway, decreased cholinergic currents and increased γ power of the amperometric cholinergic signals were accompanied by the induction of LTP and increased γ power of local field potentials. These findings indicated that some correlations may exist between amperometric cholinergic signals and synaptic plasticity in the hippocampus-mPFC pathway. The pattern of alterations in cholinergic signals may help to illustrate the specific properties of synaptic plasticity and γ oscillations in the vCA1-mPFC and the pdCA1-mPFC pathways.

Weak DCS causes a relatively strong cumulative boost of synaptic plasticity with spaced learning

BackgroundElectric fields generated during direct current stimulation (DCS) are known to modulate activity-dependent synaptic plasticity in-vitro. This provides a mechanistic explanation for the lasting behavioral effects observed with transcranial direct current stimulation (tDCS) in human learning experiments. However, previous in-vitro synaptic plasticity experiments show relatively small effects despite using strong fields compared to what is expected with conventional tDCS in humans (20 V/m vs. 1 V/m). There is therefore a need to improve the effectiveness of tDCS at realistic field intensities. Here we leverage the observation that effects of learning are known to accumulate over multiple bouts of learning, known as spaced learning. HypothesisWe propose that effects of DCS on synaptic long-term potentiation (LTP) accumulate over time in a spaced learning paradigm, thus revealing effects at more realistic field intensities. MethodsWe leverage a standard model for spaced learning by inducing LTP with repeated bouts of theta burst stimulation (TBS) in hippocampal slice preparations. We studied the cumulative effects of DCS paired with TBS at various intensities applied during the induction of LTP in the CA1 region of rat hippocampal slices. ResultsAs predicted, DCS applied during repeated bouts of theta burst stimulation (TBS) resulted in an increase of LTP. This spaced learning effect is saturated quickly with strong TBS protocols and stronger fields. In contrast, weaker TBS and the weakest electric fields of 2.5 V/m resulted in the strongest relative efficacies (12% boost in LTP per 1 V/m applied). ConclusionsWeak DCS causes a relatively strong cumulative effect of spaced learning on synaptic plasticity. Staturarion may have masked stronger effects sizes in previous in-vitro studies. Relative effect sizes of DCS are now closer in line with human tDCS experiments.

Brain-Generated 17β-Estradiol Modulates Long-Term Synaptic Plasticity in the Primary Auditory Cortex of Adult Male Rats.

Neuron-derived 17β-estradiol (E2) alters synaptic transmission and plasticity in brain regions with endocrine and non-endocrine functions. Investigations into a modulatory role of E2 in synaptic activity and plasticity have mainly focused on the rodent hippocampal formation. In songbirds, E2 is synthesized by auditory forebrain neurons and promotes auditory signal processing and memory for salient acoustic stimuli; however, the modulatory effects of E2 on memory-related synaptic plasticity mechanisms have not been directly examined in the auditory forebrain. We investigated the effects of bidirectional E2 manipulations on synaptic transmission and long-term potentiation (LTP) in the rat primary auditory cortex (A1). Immunohistochemistry revealed widespread neuronal expression of the E2 biosynthetic enzyme aromatase in multiple regions of the rat sensory and association neocortex, including A1. In A1, E2 application reduced the threshold for in vivo LTP induction at layer IV synapses, whereas pharmacological suppression of E2 production by aromatase inhibition abolished LTP induction at layer II/III synapses. In acute A1 slices, glutamate and γ-aminobutyric acid (GABA) receptor-mediated currents were sensitive to E2 manipulations in a layer-specific manner. These findings demonstrate that locally synthesized E2 modulates synaptic transmission and plasticity in A1 and suggest potential mechanisms by which E2 contributes to auditory signal processing and memory.

The Association of Brain-Derived Neurotrophic Factor with Long-Term Potentiation

: Long-term potentiation (LTP) is one of the most important topics in neuroscience. It refers to a long-lasting increase in synaptic efficacy and is considered as a molecular and cellular mechanism of learning and memory. Neurotrophins play essential roles in different processes in the central nervous system (CNS), such as synaptogenesis, survival of specific populations of neurons, and neuroplasticity. Some evidence suggests that neurotrophins also participate in the synaptic plasticity related to learning and memory formation. Brain-derived neurotrophic factor (BDNF) is an important neurotrophic factor that is extensively expressed in the hippocampus and cerebral cortex, where it promotes neuroprotection, increases synaptogenesis and neurotransmission, and mediates synapse formation and synaptic plasticity. In this review, we first focused on the research investigating the effects of BDNF on synaptic plasticity and LTP induction and then reviewed the neuronal signaling molecules employed by BDNF to promote its effects on these processes.