Bi-directional Control of Synaptic Input Summation and Spike Generation by GABAergic Inputs at the Axon Initial Segment / 神经科学通报·英文版

Differing from other subtypes of inhibitory interneuron, chandelier or axo-axonic cells form depolarizing GABAergic synapses exclusively onto the axon initial segment (AIS) of targeted pyramidal cells (PCs). However, the debate whether these AIS-GABAergic inputs produce excitation or inhibition in neuronal processing is not resolved. Using realistic NEURON modeling and electrophysiological recording of cortical layer-5 PCs, we quantitatively demonstrate that the onset-timing of AIS-GABAergic input, relative to dendritic excitatory glutamatergic inputs, determines its bi-directional regulation of the efficacy of synaptic integration and spike generation in a PC. More specifically, AIS-GABAergic inputs promote the boosting effect of voltage-activated Na+ channels on summed synaptic excitation when they precede glutamatergic inputs by >15 ms, while for nearly concurrent excitatory inputs, they primarily produce a shunting inhibition at the AIS. Thus, our findings offer an integrative mechanism by which AIS-targeting interneurons exert sophisticated regulation of the input-output function in targeted PCs.

Projection-Specific Heterogeneity of the Axon Initial Segment of Pyramidal Neurons in the Prelimbic Cortex / 神经科学通报·英文版

The axon initial segment (AIS) is a highly specialized axonal compartment where the action potential is initiated. The heterogeneity of AISs has been suggested to occur between interneurons and pyramidal neurons (PyNs), which likely contributes to their unique spiking properties. However, whether the various characteristics of AISs can be linked to specific PyN subtypes remains unknown. Here, we report that in the prelimbic cortex (PL) of the mouse, two types of PyNs with axon projections either to the contralateral PL or to the ipsilateral basal lateral amygdala, possess distinct AIS properties reflected by morphology, ion channel expression, action potential initiation, and axo-axonic synaptic inputs from chandelier cells. Furthermore, projection-specific AIS diversity is more prominent in the superficial layer than in the deep layer. Thus, our study reveals the cortical layer- and axon projection-specific heterogeneity of PyN AISs, which may endow the spiking of various PyN types with exquisite modulation.

Aligned Organization of Synapses and Mitochondria in Auditory Hair Cells / 神经科学通报·英文版

Recent studies have revealed great functional and structural heterogeneity in the ribbon-type synapses at the basolateral pole of the isopotential inner hair cell (IHC). This feature is believed to be critical for audition over a wide dynamic range, but whether the spatial gradient of ribbon morphology is fine-tuned in each IHC and how the mitochondrial network is organized to meet local energy demands of synaptic transmission remain unclear. By means of three-dimensional electron microscopy and artificial intelligence-based algorithms, we demonstrated the cell-wide structural quantification of ribbons and mitochondria in mature mid-cochlear IHCs of mice. We found that adjacent IHCs in staggered pairs differ substantially in cell body shape and ribbon morphology gradient as well as mitochondrial organization. Moreover, our analysis argues for a location-specific arrangement of correlated ribbon and mitochondrial function at the basolateral IHC pole.

Effects of ring finger and tryptophan-aspartic acid 2 on dendritic spines and synapse formation in cerebral cortex neurons of mice / 南方医科大学学报

OBJECTIVE@#To clarify the functional effects of differential expression of ring finger and tryptophan-aspartic acid 2 (RFWD2) on dendritic development and formation of dendritic spines in cerebral cortex neurons of mice.@*METHODS@#Immunofluorescent staining was used to identify the location and global expression profile of RFWD2 in mouse brain and determine the co-localization of RFWD2 with the synaptic proteins in the cortical neurons. We also examined the effects of RFWD2 over-expression (RFWD2-Myc) and RFWD2 knockdown (RFWD2-shRNA) on dendritic development, dendritic spine formation and synaptic function in cultured cortical neurons.@*RESULTS@#RFWD2 is highly expressed in the cerebral cortex and hippocampus of mice, and its expression level was positively correlated with the development of cerebral cortex neurons and dendrites. RFWD2 expression was detected on the presynaptic membrane and postsynaptic membrane of the neurons, and its expression levels were positively correlated with the length, number of branches and complexity of the dendrites. In cultured cortical neurons, RFWD2 overexpression significantly lowered the expressions of the synaptic proteins synaptophysin (P < 0.01) and postsynapic density protein 95 (P < 0.01), while RFWD2 knockdown significantly increased their expressions (both P < 0.05). Compared with the control and RFWD2-overexpressing cells, the neurons with RFWD2 knockdown showed significantly reduced number of dendritic spines (both P < 0.05).@*CONCLUSION@#RFWD2 can regulate the expression of the synaptic proteins, the development of the dendrites, the formation of the dendritic spines and synaptic function in mouse cerebral cortex neurons through ubiquitination of Pea3 family members and c-Jun, which may serve as potential treatment targets for neurological diseases.

Effect of Baihe Dihuang Decoction on synaptic plasticity of hippocampus in rats with anxious depression / 中国中药杂志

To explore the effect of Baihe Dihuang Decoction on the synaptic plasticity of hippocampal neurons in rats with anxious depression. Fifty SD rats were randomly divided into normal group, model group, venlafaxine group(6.75 mg·kg~(-1)), high-dose Baihe Dihuang Decoction group(8.64 g·kg~(-1)) and low-dose Baihe Dihuang Decoction group(4.32 g·kg~(-1)). Chronic restraint stress(6 h) combined with corticosterone(ih, 30 mg·kg~(-1)) was used to establish an anxious depression model, and 7 days after modeling, the administration started and continued for 21 days. The anxiety and depression-like behaviors of the rats were evaluated. Golgi-Cox staining and electron microscopy were used to observe the morphology and ultrastructural changes of synaptic dendrites. Immunofluorescence was used to detect the expression of hippocampal synaptic plasticity protein synapsin-1 and postsynaptic density protein 95(PSD-95). Western blot method was used to detect the expression of functional protein synaptophysin(SYP) and synaptic Ras GTPase activating protein(SynGap). The results showed that the rats in the model group had obvious anxiety and depression-like behaviors, the hip-pocampal dendritic spine density and branch length were reduced, the number of synapses was cut, and the internal structure was da-maged. The average fluorescence intensity of synapsin-1 and PSD-95 was significantly reduced and the expression of SYP and SynGap also decreased. High-dose Baihe Dihuang Decoction could significantly improve the anxiety and depression-like behaviors of model rats, relieve synaptic damage, and increase the expression of synapsin-1, PSD-95, SYP, and SynGap proteins. Therefore, we believe that Baihe Dihuang Decoction can improve anxiety and depression behaviors by regulating the synaptic plasticity of hippocampal neurons.

Steroid Receptor Coactivator 3 Regulates Synaptic Plasticity and Hippocampus-dependent Memory / 神经科学通报·英文版

Steroid hormones play important roles in brain development and function. The signaling of steroid hormones depends on the interaction between steroid receptors and their coactivators. Although the function of steroid receptor coactivators has been extensively studied in other tissues, their functions in the central nervous system are less well investigated. In this study, we addressed the function of steroid receptor coactivator 3 (SRC3) - a member of the p160 SRC protein family that is expressed predominantly in the hippocampus. While hippocampal development was not altered in Src3

The roles of GluN3-containing N-methyl-D-aspartate receptor in central nerve system / 浙江大学学报·医学版

The N-methyl-D-aspartate receptor (NMDAR) in central nerve system is mostly composed of GluN1 and GluN2 subunits. The classical NMDAR has been intensively studied. However, GluN3‑containing NMDAR is much less expressed and have atypical channel properties. Recently, accumulating evidences have revealed two types of GluN3‑containing NMDAR: glutamate-gated GluN1/GluN2/GluN3 NMDAR and glycine-gated GluN1/GluN3 NMDAR. The former may play important roles in regulating synapse maturation and pruning non-used synapses, and its elevated expression at the adult stage may alter synaptic reorganization in some neuropsychiatric disorders. The latter is expressed in the medial habenula and involves in control of aversion. This article reviews the recent progresses on the expression, functional properties of GluN3‑containing atypical NMDARs and the physiological and pathological relevance.

Privación sensorial temprana durante el neurodesarrollo y sus consecuencias cognitivas / Early sensory deprivation in neurodevelopment and its cognitive consequences / Privação sensorial precoce durante o neuro-desenvolvimento e suas consequências cognitivas

La aparición progresiva de habilidades sensoriales, motoras y cognitivo-afectivas en el humano a lo largo de su desarrollo es un reflejo de cambios fisiológicos que se gestan al interior del sistema nervioso. Dichos cambios hacen parte de procesos dinámicos y dependen, después del nacimiento, de la actividad eléctrica inducida por la experiencia. Considerando lo anterior, el sistema nervioso en desarrollo constituye una especie de protomapa, sobre el que la experiencia moldea características moleculares, neuroquímicas y de conectividad, que se reflejan en las actividades emergentes del sistema. La evidencia que soporta la importancia que la influencia experiencial tiene sobre el desarrollo del sistema nervioso viene en aumento. Esta revisión reúne información sobre estudios en modelos biológicos y en humanos sometidos a privación sensorial y ambiental. Se enfatiza en la caracterización de los rasgos cognitivos y sociales.

The progressive advent of sensory, motor, affective, and cognitive skills in the human being through its development, demonstrate physiological changes that are gestated within the nervous system. These processes are dynamic and dependent postnatally on electrical activity induced by experience. Taking this into account, the developing nervous system constitutes a protomap molded by experience dependent molecular, physiological and connectivity characteristics, which are reflected in the emergent principles of the system. The evidence that supports the importance of experience as influence over the development of this system has increased in the past years. This document gathers information about animal models and human studies enduring sensory and environmental deprivation, emphasizing in the characterization of their cognitive and social remarks.

O aparecimento progressivo de habilidades sensoriais, motoras e cognitivo-afetivas no humano ao longo do seu desenvolvimento é um reflexo de mudanças fisiológicas que se gestam no interior do sistema nervoso. Ditas mudanças fazem parte de processos dinâmicos e dependem, depois do nascimento, da atividade elétrica induzida pela experiência. Considerando o anterior, o sistema nervoso em desenvolvimento constitui uma espécie de "protomapa", sobre o que a experiência molda características moleculares, neuroquímicas e de conectividade, que se refletem nas atividades emergentes do sistema. A evidência que suporta a importância que a influência experiencial tem sobre o desenvolvimento do sistema nervoso vem em aumento. Esta revisão reúne informação sobre estudos em modelos biológicos e em humanos submetidos a privação sensorial e ambiental. Se enfatiza na caracterização das características cognitivas e sociais.

Analysis of common genetic variants associated with neuro-synapse development among 60 family trios affected with sporadic autism spectrum disorders / 中华医学遗传学杂志

OBJECTIVE@#To explore susceptibility genes for autism spectrum disorders (ASD).@*METHODS@#Whole-exome sequencing was carried out for 60 family trios affected with sporadic ASD. Genetic variants discovered in over 10% of the patients were selected for genotype-phenotype correlation and pathway enrichment analysis using Phenolyzer software and metascape database. Combining gene-phenotypic scores, pathway-related genes associated with neural and neurite triggering were screened for the candidates.@*RESULTS@#A total of 170 common variants were found to be associated with the ASD phenotype. Among these, there was only one high-confidence gene [SHANK2(0.8146)] and four medium-confidence genes [ERBB2(0.1322), LAMC3(0.1117), PPFIA4(0.1059), DISC1(0.1002)]. Twenty-pathways and four biological processes were found to be statistically significant by pathway enrichment analysis, which included neuron projection morphogenesis (GO: 0048812), regulation of neuroblast proliferation (GO: 1902692), modulation of excitatory postsynaptic potential (GO: 0098815), and dendrite morphogenesis (GO: 0048813). Twenty-one genes were found to be closely associated with neurological and neurite triggering, among which only SHANK2, ERBB2, and DISC1 had above-medium confidence correlation scores with the ASD phenotypes.@*CONCLUSION@#Abnormal neuron projection morphogenesis (GO: 0048812) may be closely related to the occurrence of ASD. SHANK2, ERBB2, and DISC1 are susceptibility genes for ASD.

Progress on the role of synaptic cell adhesion molecules in stress / 生理学报

Synaptic cell adhesion molecules (CAMs) are a type of membrane surface glycoproteins that mediate the structural and functional interactions between pre- and post-synaptic sites. Synaptic CAMs dynamically regulate synaptic activity and plasticity, and their expression and function are modulated by environmental factors. Synaptic CAMs are also important effector molecules of stress response, and mediate the adverse impact of stress on cognition and emotion. In this review, we will summarize the recent progress on the role of synaptic CAMs in stress, and aim to provide insight into the molecular mechanisms and drug development of stress-related disorders.

Comprendiendo el código neuronal: un análisis de cuatro perspectivas / Understanding the neural code: a four-perspective analysis

El objetivo de este artículo de revisión es dar a conocer diferentes perspectivas que han contribuido al estudio del Código Neuronal, un concepto que proviene de la Neurociencia y que explica el funcionamiento del cerebro a través de conexiones de neuronas. Se entregan cuatro ideas relacionadas con el análisis de este funcionamiento. En primer lugar, la propuesta de Convergencia Jerárquica, que ofrece una explicación asociada a un correlato neuronal específico para una conducta determinada. En segundo lugar, se aborda la idea del Código de Poblaciones, que explica el trabajo de un grupo de neuronas que representan un determinado estado. Posteriormente se expone la propuesta de Correlación Temporal, que plantea la presencia de poblaciones neuronales activas que se diferencian entre sí en base a patrones temporales de descarga para, finalmente, llegar al concepto de redes neuronales y sus diferentes modelos explicativos que han actuado como cimientos para el desarrollo de la Neurociencia moderna y que han sido desarrollados gracias a los aportes de la Biología, la Física, las Matemáticas, entre otras disciplinas, y que han generado las bases para la comprensión del funcionamiento del cerebro a través de neuronas interconectadas para lograr la expresión de los diferentes procesos cognitivos. El presente artículo pretende que el lector desarrolle una visión panorámica y general de cómo opera el flujo de la información que procesa el sistema nervioso central y el impacto que este fenómeno genera en el proceso de integración sensorial como parte de la emoción y la cognición en el cerebro humano.

The objective of this review article is to present different perspectives that have contributed to the study of the Neural Code, a concept that comes from Neuroscience and that explains the functioning of the brain through neuron connections. Four ideas related to the analysis of this functioning are presented. Firstly, the proposal of Hierarchical Convergence, which offers an explanation associated with a specific neuronal correlate for a specific behavior. Secondly, the idea of the Population Code is discussed, which explains the work of a group of neurons that represent a certain state. Subsequently, the proposal of Temporal Correlation is addressed, which proposes the presence of active neuronal populations that differentiate each other based on temporal discharge patterns, finally arriving at the concept of neural networks and their different explanatory models. The latter have acted as foundations for the development of modern Neuroscience and have been developed thanks to the contributions of Biology, Physics, Mathematics, among other disciplines, and have generated the basis for understanding the functioning of the brain through interconnected neurons to achieve the expression of the different cognitive processes. The paper aims to develop a panoramic and general view of how the flow of information processed by the central nervous system operates and the impact that this phenomenon generates in the process of sensory integration as part of emotion and cognition in the human brain.

Bases neurobiológicas del autismo y modelos celulares para su estudio experimental / Neurobiological bases of autism and cellular models for its experimental study

Los trastornos del espectro autista (TEA) son una alteración funcional de la corteza cerebral, que presenta anomalías estructurales del neurodesarrollo que afectan fundamentalmente a la función sináptica y el patrón de conexiones dentro y entre columnas corticales. Desde su aspecto etiológico, el TEA tiene una importante carga genética, considerándose un desorden derivado de una combinación de mutaciones "de novo", asociadas a una predisposición derivada de variaciones comunes heredadas. Las principales anomalías genéticas asociadas a TEA implican genes que codifican proteínas de la sinapsis. Así, en pacientes con TEA se han descrito alteraciones del desarrollo inicial de las sinapsis en los circuitos de conexión entre áreas corticales de procesamiento complejo. La complejidad molecular observada en la predisposición a desarrollar un TEA, junto con la diversidad de fenotipos estructurales neuronales, ha hecho que los modelos animales reproduzcan solo parcialmente el TEA. Para avanzar en el estudio experimental se hace pues necesario desarrollar modelos más representativos, como son los modelos celulares derivados de células humanas. En las últimas décadas, el desarrollo de la biología de las células madre nos da medios para acceder a paradigmas experimentales sobre células derivadas de individuos con TEA. Actualmente, los modelos de células plutipotentes inducidas (IPs) derivadas de células humanas permiten profundizar en el estudio de las bases moleculares y celulares del TEA. Sin embargo, presentan problemas inherentes derivados de la manipulación experimental que conlleva la reprogramación de la expresión génica, por lo que otros modelos celulares se están también postulando como válidos.

Autism Spectrum Disorders (ASD) are a functional alteration of the cerebral cortex, which presents structural neurodevelopmental anomalies that affect synaptic function and the pattern of connections within and between cortical columns. From its etiological aspect, ASD has an important genetic load, considering a polygenic disorder, derived from a combination of "de novo" genetic mutations, associated to a predisposition derived from common inherited variations. The main genetic anomalies associated with ASD involve genes that encode proteins of the synapse. Thus, in patients with ASD, alterations in the initial development of the synapses have been described in the connection circuits between complex processing cortical areas. The molecular complexity observed in the predisposition to develop an ASD, together with the diversity of structural phenotypes, has made animal models reproduce only partially the ASD. To advance in the experimental study it is therefore necessary to develop representative models, such as cellular models derived from human cells. In recent decades, the advances in stem cell biology give us a way to apply experimental paradigms in cells derived from individuals with ASD. Currently, induced pluripotent cells (IPs) derived from human adult cells allow deepening the study of molecular and cellular bases of the neuronal development in humans, as well as the anomalies in this development, which give rise to disorders such as ASD. However, they present inherent problems derived from the experimental manipulation that involves the reprogramming of gene expression, therefore other models are also been explored.

Role of secretory C1q protein in the formation and regulation of synapse / 生理学报

The C1q family is one of the subcomponents of the C1 complex that recognizes immune complexes and initiates the classical pathway of the complement system. In addition, as a pattern recognition receptor (PRR), the C1q family binds to a wide variety of ligands. As a member of the C1q family, the secretory C1q includes several subtypes. The main subtypes are cerebellin (Cbln) and C1q-like protein (C1ql). In the nervous system, secretory C1q is involved in the formation and regulation of various types of synapses, thus secretory C1q is closely related to diseases of the central nervous system. In this article, we review the role of secretory C1q in synapse formation and regulation, and its relationship with some diseases of the central nervous system.

Study of dynamic characteristics of scale-free spiking neural networks based on synaptic plasticity / 生物医学工程学杂志

Biological neural networks have dual properties of small-world attributes and scale-free attributes. Most of the current researches on neural networks are based on small-world networks or scale-free networks with lower clustering coefficient, however, the real brain network is a scale-free network with small-world attributes. In this paper, a scale-free spiking neural network with high clustering coefficient and small-world attribute was constructed. The dynamic evolution process was analyzed from three aspects: synaptic regulation process, firing characteristics and complex network characteristics. The experimental results show that, as time goes by, the synaptic strength gradually decreases and tends to be stable. As a result, the connection strength of the network decreases and tends to be stable; the firing rate of neurons gradually decreases and tends to be stable, and the synchronization becomes worse; the local information transmission efficiency is stable, the global information transmission efficiency is reduced and tends to be stable, and the small-world attributes are relatively stable. The dynamic characteristics vary with time and interact with each other. The regulation of synapses is based on the firing time of neurons, and the regulation of synapses will affect the firing of neurons and complex characteristics of networks. In this paper, a scale-free spiking neural network was constructed, which has biological authenticity. It lays a foundation for the research of artificial neural network and its engineering application.

Neuroligins Differentially Mediate Subtype-Specific Synapse Formation in Pyramidal Neurons and Interneurons / 神经科学通报·英文版

Neuroligins (NLs) are postsynaptic cell-adhesion proteins that play important roles in synapse formation and the excitatory-inhibitory balance. They have been associated with autism in both human genetic and animal model studies, and affect synaptic connections and synaptic plasticity in several brain regions. Yet current research mainly focuses on pyramidal neurons, while the function of NLs in interneurons remains to be understood. To explore the functional difference among NLs in the subtype-specific synapse formation of both pyramidal neurons and interneurons, we performed viral-mediated shRNA knockdown of NLs in cultured rat cortical neurons and examined the synapses in the two major types of neurons. Our results showed that in both types of neurons, NL1 and NL3 were involved in excitatory synapse formation, and NL2 in GABAergic synapse formation. Interestingly, NL1 affected GABAergic synapse formation more specifically than NL3, and NL2 affected excitatory synapse density preferentially in pyramidal neurons. In summary, our results demonstrated that different NLs play distinct roles in regulating the development and balance of excitatory and inhibitory synapses in pyramidal neurons and interneurons.

Vesicular Glutamate Transporter 1 (VGLUT1)- and VGLUT2-containing Terminals on the Rat Jaw-closing γ-Motoneurons

Currently, compared to jaw-closing (JC) α-motoneurons, the information on the distribution and morphology of glutamatergic synapses on the jaw-closing (JC) γ-motoneurons, which may help elucidate the mechanism of isometric contraction of the JC muscle, is very limited. This study investigated the distribution and ultrastructural features of vesicular glutamate transporter 1 (VGLUT1)- and VGLUT2-immunopositive (+) axon terminals (boutons) on JC γ-motoneurons by retrograde tracing with horseradish peroxidase, electron microscopic immunocytochemistry, and quantitative analysis. About 35% of the boutons on identified JC γ-motoneurons were VGLUT+, and of those, 99% were VGLUT2+. The fraction of VGLUT1+ boutons of all boutons and the percentage of membrane of JC γ-motoneurons covered by these boutons were significantly lower than those for the JC α-motoneurons, revealed in our previous work. The bouton volume, mitochondrial volume, and active zone area of the VGLUT2+ boutons on the JC γ-motoneurons were uniformly small. These findings suggest that the JC γ-motoneurons, in contrast to the JC α-motoneurons, receive generally weak glutamatergic synaptic input almost exclusively from VGLUT2+ premotoneurons that form direct synapse with motoneurons.

Basal Forebrain Cholinergic-induced Activation of Cholecystokinin Inhibitory Neurons in the Basolateral Amygdala

The basolateral amygdala (BLA) receives dense projections from cholinergic neurons of the basal forebrain. Acetylcholine can contributes to amygdala-dependent behaviors: formation and extinction of fear memory and appetitive instrumental learning. However, the cholinergic mechanism at the circuit level has not been defined yet. We demonstrated that cholinergic-induced di-synaptic inhibition of BLA pyramidal neurons exhibits a retrograde form of short-term synaptic inhibition, depolarization-induced suppression of inhibition (DSI). Activation of nicotinic receptors was sufficient to evoke action potentials in cholecystokinin (CCK)-positive inhibitory neurons, which strongly inhibit pyramidal neurons through their perisomatic synapses. Our cell type-specific monosynaptic retrograde tracing also revealed that CCK neurons are innervated by basal forebrain cholinergic neurons. Therefore, our data indicated that CCK inhibitory neurons mediate the cholinergic-induced di-synaptic inhibition of BLA pyramidal neurons.

Can we delineate preoperatively the right and ventral margins of caudate lobe of the liver?

PURPOSE: Complete removal of the caudate lobe, which is sometimes necessary, is accomplished via isolated caudate lobectomy or hepatectomy that includes the caudate lobe. It is impossible, however, to confirm the right and ventral margins of the caudate lobe by preoperative imaging. This study was undertaken to determine whether we could identify the right and ventral margins of the caudate lobe preoperatively using Synapse 3D visualization software. METHODS: Ninety-four preoperative 3-dimensional (3D) computed tomographic images (1-mm slices) of the liver from candidate donors were examined. The images of the caudate lobe were subjected to a counter-staining method according to Synapse 3D to delineate their dimensions. We first examined whether the right margin of the caudate lobe exceeded the plane formed by the root of the right hepatic vein (RHV) and the right side of the inferior vena cava (IVC). Second, we determined whether the ventral margin of the caudate lobe exceeded the plane formed by the root of the middle hepatic vein (MHV) and the root of the RHV. RESULTS: For the right margin, 17 cases (18%) exceeded the RHV-IVC plane by a mean of 10.2 mm (range, 2.4–27.2 mm). For the ventral margin, 28 cases (30%) exceeded the MHV-RHV plane by a mean of 17.4 mm (range, 1.2–49.1 mm). CONCLUSION: Evaluating the anatomy of caudate lobe using Synapse 3D preoperatively could be helpful for more precise anatomical resection of the caudate lobe.

Layer-specific cholinergic modulation of synaptic transmission in layer 2/3 pyramidal neurons of rat visual cortex

It is known that top-down associative inputs terminate on distal apical dendrites in layer 1 while bottom-up sensory inputs terminate on perisomatic dendrites of layer 2/3 pyramidal neurons (L2/3 PyNs) in primary sensory cortex. Since studies on synaptic transmission in layer 1 are sparse, we investigated the basic properties and cholinergic modulation of synaptic transmission in layer 1 and compared them to those in perisomatic dendrites of L2/3 PyNs of rat primary visual cortex. Using extracellular stimulations of layer 1 and layer 4, we evoked excitatory postsynaptic current/potential in synapses in distal apical dendrites (L1-EPSC/L1-EPSP) and those in perisomatic dendrites (L4-EPSC/L4-EPSP), respectively. Kinetics of L1-EPSC was slower than that of L4-EPSC. L1-EPSC showed presynaptic depression while L4-EPSC was facilitating. In contrast, inhibitory postsynaptic currents showed similar paired-pulse ratio between layer 1 and layer 4 stimulations with depression only at 100 Hz. Cholinergic stimulation induced presynaptic depression by activating muscarinic receptors in excitatory and inhibitory synapses to similar extents in both inputs. However, nicotinic stimulation enhanced excitatory synaptic transmission by ~20% in L4-EPSC. Rectification index of AMPA receptors and AMPA/NMDA ratio were similar between synapses in distal apical and perisomatic dendrites. These results provide basic properties and cholinergic modulation of synaptic transmission between distal apical and perisomatic dendrites in L2/3 PyNs of the visual cortex, which might be important for controlling information processing balance depending on attentional state.

Restorative Mechanism of Neural Progenitor Cells Overexpressing Arginine Decarboxylase Genes Following Ischemic Injury

Cell replacement therapy using neural progenitor cells (NPCs) following ischemic stroke is a promising potential therapeutic strategy, but lacks efficacy for human central nervous system (CNS) therapeutics. In a previous in vitro study, we reported that the overexpression of human arginine decarboxylase (ADC) genes by a retroviral plasmid vector promoted the neuronal differentiation of mouse NPCs. In the present study, we focused on the cellular mechanism underlying cell proliferation and differentiation following ischemic injury, and the therapeutic feasibility of NPCs overexpressing ADC genes (ADC-NPCs) following ischemic stroke. To mimic cerebral ischemia in vitro , we subjected the NPCs to oxygen-glucose deprivation (OGD). The overexpressing ADC-NPCs were differentiated by neural lineage, which was related to excessive intracellular calcium-mediated cell cycle arrest and phosphorylation in the ERK1/2, CREB, and STAT1 signaling cascade following ischemic injury. Moreover, the ADC-NPCs were able to resist mitochondrial membrane potential collapse in the increasingly excessive intracellular calcium environment. Subsequently, transplanted ADC-NPCs suppressed infarct volume, and promoted neural differentiation, synapse formation, and motor behavior performance in an in vivo tMCAO rat model. The results suggest that ADC-NPCs are potentially useful for cell replacement therapy following ischemic stroke.