Synaptic Changes Research Articles

DNA Methylation and Histone Acetylation Contribute to the Maintenance of LTP in the Withdrawal Behavior Interneurons in Terrestrial Snails

Accumulated data indicate that epigenetic regulations, including histone modifications and DNA methylation, are important means for adjusting the expression of genes in response to various stimuli. In contrast to the success in studying the role of DNA methylation in laboratory rodents, the role of DNA methylation in the terrestrial snail Helix lucorum has been studied only in behavioral experiments. This prompted us to further investigate the role of DNA methylation and the interaction between DNA methylation and histone acetylation in the mechanisms of neuroplasticity in terrestrial snails using in vitro experiments. Dysregulation of DNA methylation by the DNMT inhibitor RG108 significantly suppressed the long-term potentiation (LTP) of synaptic inputs in identified neurons. We then tested whether the RG108-induced weakening of potentiation can be reversed under co-application of histone deacetylase inhibitors sodium butyrate or trichostatin A. It was found that increased histone acetylation significantly compensated for RG108-induced LTP deficiency. These data bring important insights into the functional role of DNA methylation as an important regulatory mechanism and a necessary condition for the development and maintenance of long-term synaptic changes in withdrawal interneurons of terrestrial snails. Moreover, these results support the idea of the interaction of DNA methylation and histone acetylation in the epigenetic regulation of synaptic plasticity.

Decreased Expression of the EAAT5 Glutamate Transporter at Photoreceptor Synapses in Early, Pre-Clinical Experimental Autoimmune Encephalomyelitis, a Mouse Model of Multiple Sclerosis

Background: Multiple sclerosis is a frequent neuroinflammatory and neurodegenerative disease of the central nervous system that includes alterations in the white and gray matter of the brain. The visual system is frequently affected in multiple sclerosis. Glutamate excitotoxicity might play a role in disease pathogenesis. Methodology: In the present study, we analyzed with qualitative and quantitative immunofluorescence microscopy and Western blot analyses whether alterations in the EAAT5 (SLC1A7) glutamate transporter could be involved in the previously observed alterations in structure and function of glutamatergic photoreceptor ribbon synapses in the EAE mouse model of MS. EAAT5 is a presynaptic glutamate transporter located near the presynaptic release sites. Results: We found that EAAT5 was strongly reduced at the photoreceptor synapses of EAE retinas in comparison to the photoreceptor synapses of the respective control retinas as early as day 9 post-immunization. The Western blot analyses demonstrated a decreased EAAT5 expression in EAE retinas. Conclusions: Our data illustrate early alterations of the EAAT5 glutamate transporter in the early pre-clinical phase of EAE/MS and suggest an involvement of EAAT5 in the previously observed early synaptic changes at photoreceptor synapses. The precise mechanisms need to be elucidated by future investigations.

Synaptopodin: a key regulator of Hebbian plasticity

Synaptopodin, an actin-associated protein found in a subset of dendritic spines in telencephalic neurons, has been described to influence both functional and morphological plasticity under various plasticity paradigms. Synaptopodin is necessary and sufficient for the formation of the spine apparatus, stacks of smooth endoplasmic reticulum cisternae. The spine apparatus is a calcium store that locally regulates calcium dynamics in response to different patterns of activity and is also thought to be a site for local protein synthesis. Synaptopodin is present in ~30% of telencephalic large dendritic spines in vivo and in vitro highlighting the heterogeneous microanatomy and molecular architecture of dendritic spines, an important but not well understood aspect of neuroplasticity. In recent years, it has become increasingly clear that synaptopodin is a formidable regulator of multiple mechanisms essential for learning and memory. In fact, synaptopodin appears to be the decisive factor that determines whether plasticity can occur, acting as a key regulator for synaptic changes. In this review, we summarize the current understanding of synaptopodin’s role in various forms of Hebbian synaptic plasticity.

Experience-driven competition in neural reorganization after stroke.

Behavioural experiences interact with regenerative responses to shape patterns of neural reorganization after stroke. This review is focused on the competitive nature of these behavioural experience effects. Interactions between learning-related plasticity and regenerative reactions have been found to underlie the establishment of new compensatory behaviours and the efficacy of motor rehabilitative training in rodent stroke models. Learning in intact brains depends on competitive and cooperative mechanisms of synaptic plasticity. Synapses are added in response to learning and selectively maintained and strengthened via activity-dependent competition. Long-term memories for experiences that occur closely in time can be weakened or enhanced by competitive or cooperative interactions in the time-dependent process of stabilizing synaptic changes. Rodent stroke model findings suggest that compensatory reliance on the non-paretic hand after stroke can shape and stabilize synaptic reorganization patterns in both hemispheres, to compete with the capacity for experiences of the paretic side to do so. However, the competitive edge of the non-paretic side can be countered by overlapping experiences of the paretic hand, and might even be shifted in a cooperative direction with skilfully coordinated bimanual experience. Advances in the basic understanding of learning-related synaptic competition are helping to inform the basis of experience-dependent variations in stroke outcome.

Reducing Synaptic Plasticity Decreases Resilience to Depression and Anxiety in an ASCL1 Mouse Model

Synaptic plasticity, the ability of synapses to strengthen or weaken over time in response to activity, plays a crucial role in the brain’s adaptability and function. This paper examines the impact of synaptic plasticity on resilience to depression and anxiety in an ASCL1 mouse model. By studying the molecular and cellular mechanisms of synaptic changes, how these changes affect behavioral outcomes related to stress and emotional regulation analysis. Through the research and findings of this paper, a deeper understanding of the relationship between the enhancement of synaptic plasticity and mood changes, and provide more treatment ideas for depression and emotion-related diseases.

LF-DBS of the ventral striatum shortens persistence for morphine place preference and modulates BDNF expression in the hippocampus

BackgroundDeep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) represents a promising therapy for treatment-refractory patients with substance-use disorders. We previously found that low-frequency (LF) DBS aimed to the VC/VS during extinction training strengthens the extinction memory for morphine seeking under a partial extinction protocol. Objectives/HypothesisIn this study, animals were tested in a full extinction protocol to determine whether LF-DBS applied during extinction facilitates extinction while preventing drug reinstatement, and study the molecular mechanisms underlying the effects of LF-DBS, Methods/ResultsWe used a full extinction CPP paradigm combined with LF-DBS to assess behavior. Western blots for the pro-extinction molecule, brain-derived neurotrophic factor (BDNF) were then performed in corticomesolimbic regions of the brain. Lastly, to determine whether changes in BDNF expression elicited by LF-DBS were specific to the VS/NAc afferents from the hippocampus, amygdala, and medial prefrontal cortex, we performed BDNF-like immunohistochemistry, combined with the retrograde tracer cholera toxin B (CtB). ResultsWe showed a significant reduction in the number of days required to fully extinguish morphine CPP in animals exposed to LF-DBS during extinction training accompanied by a significant increase in BDNF expression in the hippocampus. However, LF-DBS applied during extinction did not prevent drug reinstatement. Lastly, no changes in BDNF/CtB double-labeled cells were found in VS/NAc projecting cells after one-day exposure to LF-DBS. Conclusion(s)These data suggest that LF-DBS can facilitate extinction of morphine CPP by decreasing drug seeking through potential synaptic plasticity changes in the hippocampus to strengthen extinction memories.

NeuropsychopharmARCology: Shaping Neuroplasticity through Arc/Arg3.1 Modulation

Activity-regulated cytoskeletal associated protein (aka activity-regulated gene Arg3.1) belongs to the effector gene family of the immediate early genes. This family encodes effector proteins, which act directly on cellular homeostasis and function. Arc/Arg3.1 is localized at dendritic processes, allowing the protein local synthesis on demand, and it is considered a reliable index of activitydependent synaptic changes. Evidence also exists showing the critical role of Arc/Arg3.1 in memory processes. The high sensitivity to changes in neuronal activity, its specific localization as well as its involvement in long-term synaptic plasticity indeed make this effector gene a potential, critical target of the action of psychotropic drugs. In this review, we focus on antipsychotic and antidepressant drugs as well as on psychostimulants, which belong to the category of drugs of abuse but can also be used as drugs for specific disorders of the central nervous system (i.e., Attention Deficit Hyperactivity Disorder). It is demonstrated that psychotropic drugs with different mechanisms of action converge on Arc/Arg3.1, providing a means whereby Arc/Arg3.1 synaptic modulation may contribute to their therapeutic activity. The potential translational implications for different neuropsychiatric conditions are also discussed, recognizing that the treatment of these disorders is indeed complex and involves the simultaneous regulation of several dysfunctional mechanisms.

Altered Expression of Neuroplasticity-Related Genes in Alcohol Addiction and Treatment

Alcohol use disorder’s complexity arises from genetic and environmental factors, with alcohol metabolism genes and neurotransmitter pathways being critical. This study aims to analyze synaptic plasticity gene expression changes in individuals with AUD in order to study their contribution to AUD development and to identify potential biomarkers of treatment response. RNA was extracted from whole peripheral blood (20 patients, 10 healthy controls), before and after treatment (Qiagen AllPrep RNA/DNA Mini Kit), and the gene expression of 84 genes related to neuroplasticity was studied using the RT2 Profiler for Human Synaptic Plasticity RT-PCR Array (PAHS-126ZA, Qiagen), comparing AUD patients to control and responders to non-responders. The potential prognostic/predictive biomarkers were searched using machine learning models. A total of 35 dysregulated genes were found in AUD patients. EPHB2, EGR, and AKT1 were increased, while TIMP1, NCAM1, and GRM2 were decreased. Responders showed distinct gene expression profiles at baseline. After treatment, the expression of 57 genes was normalized, while NCAM1, GRM2, and BDNF showed the most significant recovery. EGR4, INHBA, and NCAM1 emerged as potential biomarkers to predict treatment success. These results indicate that gene profiles in peripheral blood can serve as prognostic markers for the prognosis and treatment of AUD, although further validation is required.

Distinct modulation of Ih by synaptic potentiation in excitatory and inhibitory neurons.

Selective modifications in the expression or function of dendritic ion channels regulate the propagation of synaptic inputs and determine the intrinsic excitability of a neuron. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels open upon membrane hyperpolarization and conduct a depolarizing inward current (Ih). HCN channels are enriched in the dendrites of hippocampal pyramidal neurons where they regulate the integration of synaptic inputs. Synaptic plasticity can bidirectionally modify dendritic HCN channels in excitatory neurons depending on the strength of synaptic potentiation. In inhibitory neurons, however, the dendritic expression and modulation of HCN channels is largely unknown. In this study, we systematically compared the modulation of Ih by synaptic potentiation in hippocampal CA1 pyramidal neurons and stratum Radiatum (sRad) interneurons in mouse organotypic cultures. Ih properties were similar in inhibitory and excitatory neurons and contributed to resting membrane potential and action potential firing. We found that in sRad interneurons, HCN channels were downregulated after synaptic plasticity, irrespective of the strength of synaptic potentiation. This suggest differential regulation of Ih in excitatory and inhibitory neurons, possibly signifying their distinct role in network activity.Significance statement Learning reflects a change in the way information is processed in neuronal circuits. This occurs via changes in synaptic connections and via alterations of intrinsic excitability of neurons. Here we examined how synaptic changes affect properties of HCN channels, which are important ion channels for intrinsic excitability. We found that strong synaptic potentiation leads to opposite changes in HCN channels in CA1 pyramidal neurons and sRad interneurons. We speculate that this reflects their differential role in the CA1 network. An upregulation of HCN channels in pyramidal neurons results in a decrease in their excitability, which limits overall network excitation. In contrast, sRad interneurons show downregulation of Ih, and therefore an increased excitability after strong synaptic activation, which will strengthen feedforward inhibition and sharpen activity patterns.

Markov Blankets and Cognitive Dysfunction in mTBI: Insights from Simulation Models

<p>Mild Traumatic Brain Injury (mTBI) is a prevalent neurological condition that can lead to persistent cognitive impairments, disrupting memory, attention, and executive function. In this study, we explore the mechanisms of cognitive decline in mTBI through the lens of Markov blankets—a theoretical framework that delineates the statistical boundary between the brain’s internal and external states. By simulating the impact of mTBI on sensory, active, internal, and external states, we demonstrate how disruptions to the Markov blanket structure contribute to impairments in predictive coding and cognitive processing. Our simulation introduces noise and connectivity reductions that mimic the neurometabolic and synaptic changes following mTBI, revealing delayed sensory processing, impaired motor function, and cognitive instability. These findings highlight the importance of Markov blankets in maintaining cognitive integrity and offer novel insights into the pathophysiology of post-concussion syndrome. Understanding how mTBI disrupts the brain's functional architecture through Markov blanket disturbances may inform more effective diagnostic and therapeutic approaches.</p>

9325 Obesity Alters Pomc And Kisspeptin Neuron Crosstalk Leading To Lower Luteinizing Hormone

Abstract Disclosure: P. Villa: None. R. Ruggiero-Ruff: None. B. Jamieson: None. R. Campbell: None. D. Coss: None. Obesity is a significant public health concern due to its high prevalence and numerous comorbidities. It is associated with hypogonadism in males, characterized by low testosterone and sperm number. Previous studies determined that these stem from dysregulation of hypothalamic circuitry that regulates reproduction, by unknown mechanisms, since studies are confounded by chronic nature of this condition that leads to synaptic changes and alterations in neuron responsiveness to stimuli. Herein, we used mice fed chronic high-fat diet, that mimics human obesity, to determine mechanisms of impairment at the level of the hypothalamus, in particular gonadotropin-releasing hormone (GnRH) neurons that regulate luteinizing hormone levels (LH), which in turn regulates testosterone synthesis. Consistent with obese humans, we demonstrated lower LH, and lower pulse frequency of LH secretion, but unchanged pituitary responsiveness to GnRH. Pulse frequency of LH is regulated by pulsatile GnRH secretion, which is controlled by kisspeptin. Peripheral and central kisspeptin injections, and DREADD-mediated activation of kisspeptin neurons, demonstrated that kisspeptin neurons were suppressed in obese mice. Thus, we investigated regulators of kisspeptin secretion. We determined that LH response to NMDA was lower in obese mice, corresponding to fewer glutamate receptors in kisspeptin neurons, which may be critical for kisspeptin synchronization. Given that kisspeptin neurons also interact with POMC neurons, which regulate satiety and are particularly affected by obesity, we examined their crosstalk, and determined that LH response to either DREADD-mediated activation of POMC neurons or central injection of αMSH, a product of POMC, is abolished in obese mice. This was accompanied by diminished levels of αMSH receptor, MC4R, in kisspeptin neurons. The reason may be that chronically higher activity of POMC neurons in response to obesity, downregulates αMSH receptors on target neurons, including kisspeptin. This may lead to suppression of kisspeptin neurons, and their inability to regulate pulsatile secretion of GnRH. Together, our studies determined that obesity leads to downregulation of receptors that regulate kisspeptin neurons, which is associated with lower LH pulse frequency, leading to lower LH and hypogonadism. Presentation: 6/2/2024

Crucial role of Snf7-3 in synaptic function and cognitive behavior revealed by conventional and conditional knockout mouse models

Snf7-3 is a crucial component of the endosomal sorting complexes required for transport (ESCRT) pathway, playing a vital role in endolysosomal functions. To elucidate the role of Snf7-3 in vivo, we developed conventional-like and conditional Snf7-3 knockout (KO) mouse models using a “Knockout-first” strategy. Conventional-like Snf7-3 KO mice showed significantly reduced Snf7-3 mRNA expression, and older mice (25–40 weeks) exhibited impaired social recognition and increased miniature excitatory postsynaptic currents (mEPSCs). Similarly, conditional KO mice aged 8–24 weeks, with Snf7-3 specifically deleted in forebrain excitatory neurons, displayed impaired object location memory and elevated mEPSC frequency. Consistently, Snf7-3 knockdown in cultured mouse hippocampal neurons led to increased densities of pre- and postsynaptic puncta, supporting the observed increase in mEPSC frequency. In addition, enhanced dendritic complexity was observed in the medial prefrontal cortex of these mice, indicating early synaptic disturbances. Our findings underscore the critical role of Snf7-3 in maintaining normal cognitive functions and social behaviors. The observed synaptic and behavioral deficits in both conventional-like and conditional KO mice highlight the importance of Snf7-3 in specific neuronal populations, suggesting that early synaptic changes could precede more pronounced cognitive impairments.

Synaptic weight dynamics underlying memory consolidation: Implications for learning rules, circuit organization, and circuit function

Systems consolidation is a common feature of learning and memory systems, in which a long-term memory initially stored in one brain region becomes persistently stored in another region. We studied the dynamics of systems consolidation in simple circuit architectures with two sites of plasticity, one in an early-learning and one in a late-learning brain area. We show that the synaptic dynamics of the circuit during consolidation of an analog memory can be understood as a temporal integration process, by which transient changes in activity driven by plasticity in the early-learning area are accumulated into persistent synaptic changes at the late-learning site. This simple principle naturally leads to a speed-accuracy tradeoff in systems consolidation and provides insight into how the circuit mitigates the stability-plasticity dilemma of storing new memories while preserving core features of older ones. Furthermore, it imposes two constraints on the circuit. First, the plasticity rule at the late-learning site must stably support a continuum of possible outputs for a given input. We show that this is readily achieved by heterosynaptic but not standard Hebbian rules. Second, to turn off the consolidation process and prevent erroneous changes at the late-learning site, neural activity in the early-learning area must be reset to its baseline activity. We provide two biologically plausible implementations for this reset that propose functional roles in stabilizing consolidation for core elements of the cerebellar circuit.

PEDOT:PSS Wire: A Two-Terminal Synaptic Device for Operation in Electrolyte and Saline Solutions.

Synaptic devices, which are designed to emulate the synaptic functions of neurons, have recently gained attention as key elements in the development of neuromorphic hardware. To date, most synaptic devices utilizing conductive polymer materials, particularly poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS), have been designed as three-terminal devices. Nevertheless, a recent study revealed that a single PEDOT:PSS wire can function as a two-terminal synaptic device through additional polymerization, which creates asymmetry in the wire diameter between the anode and cathode. Owing to its high biocompatibility, PEDOT is considered a promising candidate for use in clinical information-processing devices. However, previous studies examined the synaptic function of PEDOT:PSS only in PSS solutions. Therefore, the performance of PEDOT:PSS wires in other solutions, such as physiological saline solutions, remains unknown. Herein, we investigated the effects of operating environmental conditions (including phosphate-buffered saline (PBS)) on the synaptic functions of the asymmetric PEDOT:PSS wire. Our results indicate that the synaptic conductance change in the PEDOT:PSS wire occurred in all investigated aqueous electrolyte solutions. Moreover, we revealed the relationship between the synaptic conductance change behavior and the molecular properties of the electrolyte ions. Furthermore, the waveform of the conductance change can be controlled by adjusting the conditions for wire asymmetrization. These results demonstrate that the PEDOT:PSS wire exhibits a synaptic conductance change, yielding a waveform suitable for machine learning, even under wet conditions (i.e., in any electrolyte solution, including PBS). Therefore, PEDOT:PSS wire is a promising material for two-terminal synaptic devices applicable in clinical studies.

Neuroimaging Insights into Autism Spectrum Disorder: Structural and Functional Brain

Autism Spectrum Disorder (ASD) is a condition that affects social communication, behavior, and interests. This review analyzes recent brain imaging studies to understand the biological basis of ASD. Studies using structural magnetic resonance imaging (sMRI) show that people with ASD often have less gray matter in key brain areas like the amygdala and superior temporal sulcus. There are also concerns with white matter connections in the brain. Functional magnetic resonance imaging (fMRI)studies show reduced connectivity within critical brain networks and irregular activation patterns when processing social information. Intervention studies suggest that targeted training can improve brain function related to social skills. Postmortem research reveals cellular and synaptic changes, such as fewer Purkinje cells and altered neuron organization. These findings highlight the importance of studying the social brain network in ASD and suggest the need for more long-term, comprehensive studies. This review is intended to contribute to the development of advanced diagnostic tools and therapies that will ultimately enhance the quality of life for individuals with ASD.

Full‐vdW Heterosynaptic Memtransistor with the Ferroelectric Inserted Functional Layer and its Neuromorphic Applications

AbstractThe emergence of 2D van der Waals (vdW) materials, owing to highly tunable electrical conductivity, remarkably free stackability, and excellent compatibility for heterojunction integration, has provided abundant research diversity of artificial synapses. Here, an innovative 2D vdW heterosynaptic memtransistor (vdW‐HT) synapse is proposed with a ferroelectric CuInP2S6 inserted layer. Neuromorphic synaptic weight change of the vdW‐HT synapse in this work are modulated by the synergistic effects of interlayer coupling and ferroelectric polarization reversal. It is the first time to evaluate the required initial energy consumption of ferroelectric vdW‐HT synapses with matrixed biomimetic characteristics of “Learning–Forgetting–Re‐learning–Memorizing.” The required initial energy consumption is only ≈3.06 pJ, which provided supporting evidence to indicate the promising potential of vdW‐HT synapses in exploring neuromorphic applications. A vdW‐HT computing system with artificial recognition capability for intelligent automobiles is established and demonstrated outstanding recognition abilities for multiple targets in various environments. The highest recognition accuracy for pedestrians is 98%. In addition, the excellent recognition property is integrated with a robotic arm, successfully achieving high‐precision grasping behavior and designated position transmission for identified targets. These results provide promising strategies for the integrated development of emerging neuromorphic electronics and industrial applications.

Behavioral regression in shank3Δex4-22 mice during early adulthood corresponds to cerebellar granule cell glutamatergic synaptic changes.

Shank3, a gene encoding a synaptic scaffolding protein, is implicated in autism spectrum disorder (ASD) and is disrupted in Phelan-McDermid syndrome (PMS). Despite evidence of regression or worsening of ASD-like symptoms in individuals with PMS, the underlying mechanisms remain unclear. Although shank3 is highly expressed in the cerebellar cortical granule cells, its role in cerebellar function and contribution to behavioral deficits in ASD models are unknown. This study investigates behavioral changes and cerebellar synaptic alterations in shank3 Δex4-22 mice at two developmental stages. Shank3 Δex4-22 wildtype, heterozygous, and homozygous knockout mice lacking exons 4-22 (all functional isoforms) were subjected to a behavioral battery in both juvenile (5-7 weeks old) and adult (3-5 months old) mouse cohorts of both sexes. Immunostaining was used to show the expression of SHANK3 in the cerebellar cortex. Spontaneous excitatory postsynaptic currents (sEPSCs) from cerebellar granule cells (CGCs) were recorded by whole-cell patch-clamp electrophysiology. Deletion of shank3 ex4-22 caused deficits in motor function, heightened anxiety, and repetitive behaviors. These genotype-dependent behavioral alterations were more prominent in adult mice than in juveniles. Reduced social preference was only identified in adult shank3 Δex4-22 knockout mice and self-grooming was uniquely elevated only in males across both age groups. Immunofluorescence staining indicates the presence of SHANK3 predominantly in the dendrite-containing rosette-like structures in CGCs, colocalizing with presynaptic markers of glutamatergic mossy fiber. Electrophysiological findings identify a parallel relationship between the age-related exacerbation of behavioral impairments and the enhancement of sEPSC amplitude in CGCs. Other behavioral tests of muscle strength (grip strength test), memory (Barnes/water maze), and communication (ultrasonic vocalization), were not performed. Further study is necessary to elucidate how SHANK3 modulates synaptic function at the mossy fiber-granule cell synapse in the cerebellum. Our findings reveal an age-related exacerbation of behavioral impairments in shank3 Δex4-22 mutant mice. These results suggest that SHANK3 may play a role in maintaining glutamatergic receptors and synapses in CGCs, as well as the potential involvement of the cerebellum in ASD.

Activity in the dorsal hippocampus-mPFC circuit modulates stress-coping strategies during inescapable stress

Anatomical connectivity and lesion-deficit studies have shown that the dorsal and ventral hippocampi contribute to cognitive and emotional processes, respectively. However, the role of the dorsal hippocampus (dHP) in emotional or stress-related behaviors remains unclear. Here, we showed that neuronal activity in the dHP affects stress-coping behaviors in mice via excitatory projections to the medial prefrontal cortex (mPFC). The antidepressant ketamine rapidly induced c-Fos expression in both the dorsal and ventral hippocampi. The suppression of GABAergic transmission in the dHP-induced molecular changes similar to those induced by ketamine administration, including eukaryotic elongation factor 2 (eEF2) dephosphorylation, brain-derived neurotrophic factor (BDNF) elevation, and extracellular signal-regulated kinase (ERK) phosphorylation. These synaptic and molecular changes in the dHP induced a reduction in the immobility time of the mice in the tail-suspension and forced swim tests without affecting anxiety-related behavior. Conversely, pharmacological and chemogenetic potentiation of inhibitory neurotransmission in the dHP CA1 region induced passive coping behaviors during the tests. Transneuronal tracing and electrophysiology revealed monosynaptic excitatory connections between dHP CA1 neurons and mPFC neurons. Optogenetic stimulation of dHP CA1 neurons in freely behaving mice produced c-Fos induction and spike firing in the mPFC neurons. Chemogenetic activation of the dHP-recipient mPFC neurons reversed the passive coping behaviors induced by suppression of dHP CA1 neuronal activity. Collectively, these results indicate that neuronal activity in the dHP modulates stress-coping strategies to inescapable stress and contributes to the antidepressant effects of ketamine via the dHP-mPFC circuit.

Competitive processes shape multi-synapse plasticity along dendritic segments

Neurons receive thousands of inputs onto their dendritic arbour, where individual synapses undergo activity-dependent plasticity. Long-lasting changes in postsynaptic strengths correlate with changes in spine head volume. The magnitude and direction of such structural plasticity - potentiation (sLTP) and depression (sLTD) - depend upon the number and spatial distribution of stimulated synapses. However, how neurons allocate resources to implement synaptic strength changes across space and time amongst neighbouring synapses remains unclear. Here we combined experimental and modelling approaches to explore the elementary processes underlying multi-spine plasticity. We used glutamate uncaging to induce sLTP at varying number of synapses sharing the same dendritic branch, and we built a model incorporating a dual role Ca2+-dependent component that induces spine growth or shrinkage. Our results suggest that competition among spines for molecular resources is a key driver of multi-spine plasticity and that spatial distance between simultaneously stimulated spines impacts the resulting spine dynamics.

Progress of researches on the mechanism of acupuncture treatment for Alzheimer's disease by modulating synaptic plasticity.

Alzheimer's disease (AD) is a neurodegenerative disease with high incidence in the elderly population, and the synaptic changes in central neurons are the key pathological feature. The clinical effect of acupuncture and moxibustion in the treatment of AD is positive, and the research on the mechanism of acupuncture intervention of AD from the perspective of central synaptic plasticity regulation has been conducted uninterruptedly. In the present paper, we made a summation about the relevant experimental studies in recent years, and analyzed its mechanisms underlying improvement of AD by regulating synaptic plasticity from 1) repairing synaptic structure (synaptic contact area ［total number of synapses, synaptic surface density, synaptic number density］, postsynaptic dense zone thickness, synaptic gap width, and interface curvature), 2) improving synaptic transmission efficiency (regulating long-term potentiation and long-term depression), 3) promoting the expression of synapse related proteins (synaptophysin, postsynaptic density protein 95, growth associated protein 43), 4) regulating the expression of neurotransmitters (acetylcholine, monoamines, amino acids, etc.) and receptors (α7 nicotinic acetylcholine receptor, glutaminergic receptor, etc.), and 5) improving the level of neurotrophic factors (brain derived neurotrophic factor, BDNF) and BDNF/SYN/microtubule-associated protein 2 signaling, etc., hoping to provide a reference for future studies.