Frontiers in Synaptic Neuroscience最新文献

{"title":"Blast-Induced Mild Traumatic Brain Injury Alterations of Corticotropin-Releasing Factor Neuronal Activity in the Mouse Hypothalamic Paraventricular Nucleus.","authors":"Sarah Simmons,&nbsp;Ludovic D Langlois,&nbsp;Mario G Oyola,&nbsp;Shawn Gouty,&nbsp;T John Wu,&nbsp;Fereshteh S Nugent","doi":"10.3389/fnsyn.2021.804898","DOIUrl":"https://doi.org/10.3389/fnsyn.2021.804898","url":null,"abstract":"<p><p>Blast-induced mild traumatic brain injury (mbTBI) is the most common cause of TBI in US service members and veterans. Those exposed to TBI are at greater risk of developing neuropsychiatric disorders such as posttraumatic stress disorder, anxiety and depressive disorders, and substance use disorders following TBI. Previously, we have demonstrated that mbTBI increases anxiety-like behaviors in mice and dysregulates stress at the level of corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus (PVN). To expand on how mTBI may dysregulate the stress axis centrally, here PVN CRF neuronal activity was evaluated using whole cell-patch clamp recordings in hypothalamic slices from sham and mbTBI adult male CRF:tdTomato mice 7 days post-injury. We found that mbTBI generally did not affect the neuronal excitability and intrinsic membrane properties of PVN CRF neurons; this injury selectively increased the frequency of spontaneous neuronal firing of PVN CRF neurons localized to the dorsal PVN (dPVN) but not ventral PVN (vPVN). Consistently, mbTBI-induced dPVN CRF hyperactivity was associated with pre- and post-synaptic depression of spontaneous GABAergic transmission onto dPVN CRF neurons suggesting that mbTBI-induced GABAergic synaptic dysfunction may underlie dPVN CRF neuronal hyperactivity and increases in dPVN CRF signaling. The present results provide the first evidence for mbTBI-induced alterations in PVN CRF neuronal activity and GABAergic synaptic function that could mediate hypothalamic CRF dysregulation following mbTBI contributing to stress psychopathology associated with blast injury.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"804898"},"PeriodicalIF":3.7,"publicationDate":"2022-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8828487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39790265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transsynaptic Long-Term Potentiation in the Hippocampus of Behaving Mice.","authors":"Maria Teresa Romero-Barragán,&nbsp;Agnes Gruart,&nbsp;José M Delgado-García","doi":"10.3389/fnsyn.2021.811806","DOIUrl":"https://doi.org/10.3389/fnsyn.2021.811806","url":null,"abstract":"<p><p>Long-term potentiation (LTP) is an experimental procedure that shares certain mechanisms with neuronal learning and memory processes and represents a well-known example of synaptic plasticity. LTP consists of an increase of the synaptic response to a control stimulus following the presentation of a high-frequency stimulation (HFS) train to an afferent pathway. This technique is studied mostly in the hippocampus due to the latter's high susceptibility and its laminar nature which facilitates the location of defined synapses. Although most preceding studies have been performed <i>in vitro</i>, we have developed an experimental approach to carry out these experiments in alert behaving animals. The main goal of this study was to confirm the existence of synaptic changes in strength in synapses that are post-synaptic to the one presented with the HFS. We recorded field excitatory post-synaptic potentials (fEPSPs) evoked in five hippocampal synapses, from both hemispheres, of adult male mice. HFS was presented to the perforant pathway (PP). We characterized input/output curves, paired-pulse stimulation, and LTP of these synapses. We also performed depth-profile recordings to determine differences in fEPSP latencies. Collected data indicate that the five selected synapses have similar basic electrophysiological properties, a fact that enables an easier comparison of LTP characteristics. Importantly, we observed the presence of significant LTP in the contralateral CA1 (cCA1) area following the control stimulation of non-HFS-activated pathways. These results indicate that LTP appears as a physiological process present in synapses located far away from the HFS-stimulated afferent pathway.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"811806"},"PeriodicalIF":3.7,"publicationDate":"2022-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39894175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spindle-Shaped Neurons in the Human Posteromedial (Precuneus) Cortex.","authors":"Francisco Javier Fuentealba-Villarroel,&nbsp;Josué Renner,&nbsp;Arlete Hilbig,&nbsp;Oliver J Bruton,&nbsp;Alberto A Rasia-Filho","doi":"10.3389/fnsyn.2021.769228","DOIUrl":"https://doi.org/10.3389/fnsyn.2021.769228","url":null,"abstract":"<p><p>The human posteromedial cortex (PMC), which includes the precuneus (PC), represents a multimodal brain area implicated in emotion, conscious awareness, spatial cognition, and social behavior. Here, we describe the presence of Nissl-stained elongated spindle-shaped neurons (suggestive of von Economo neurons, VENs) in the cortical layer V of the anterior and central PC of adult humans. The adapted \"single-section\" Golgi method for <i>postmortem</i> tissue was used to study these neurons close to pyramidal ones in layer V until merging with layer VI polymorphic cells. From three-dimensional (3D) reconstructed images, we describe the cell body, two main longitudinally oriented ascending and descending dendrites as well as the occurrence of spines from proximal to distal segments. The primary dendritic shafts give rise to thin collateral branches with a radial orientation, and pleomorphic spines were observed with a sparse to moderate density along the dendritic length. Other spindle-shaped cells were observed with straight dendritic shafts and rare branches or with an axon emerging from the soma. We discuss the morphology of these cells and those considered VENs in cortical areas forming integrated brain networks for higher-order activities. The presence of spindle-shaped neurons and the current discussion on the morphology of putative VENs address the need for an in-depth neurochemical and transcriptomic characterization of the PC cytoarchitecture. These findings would include these spindle-shaped cells in the synaptic and information processing by the default mode network and for general intelligence in healthy individuals and in neuropsychiatric disorders involving the PC in the context of the PMC functioning.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"769228"},"PeriodicalIF":3.7,"publicationDate":"2022-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8787311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39955289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypothesis Relating the Structure, Biochemistry and Function of Active Zone Material Macromolecules at a Neuromuscular Junction.","authors":"Joseph A Szule","doi":"10.3389/fnsyn.2021.798225","DOIUrl":"https://doi.org/10.3389/fnsyn.2021.798225","url":null,"abstract":"<p><p>This report integrates knowledge of <i>in situ</i> macromolecular structures and synaptic protein biochemistry to propose a unified hypothesis for the regulation of certain vesicle trafficking events (i.e., docking, priming, Ca²⁺-triggering, and membrane fusion) that lead to neurotransmitter secretion from specialized \"active zones\" of presynaptic axon terminals. Advancements in electron tomography, to image tissue sections in 3D at nanometer scale resolution, have led to structural characterizations of a network of different classes of macromolecules at the active zone, called \"Active Zone Material'. At frog neuromuscular junctions, the classes of Active Zone Material macromolecules \"top-masts\", \"booms\", \"spars\", \"ribs\" and \"pins\" direct synaptic vesicle docking while \"pins\", \"ribs\" and \"pegs\" regulate priming to influence Ca²⁺-triggering and membrane fusion. Other classes, \"beams\", \"steps\", \"masts\", and \"synaptic vesicle luminal filaments' likely help organize and maintain the structural integrity of active zones. Extensive studies on the biochemistry that regulates secretion have led to comprehensive characterizations of the many conserved proteins universally involved in these trafficking events. Here, a hypothesis including a partial proteomic atlas of Active Zone Material is presented which considers the common roles, binding partners, physical features/structure, and relative positioning in the axon terminal of both the proteins and classes of macromolecules involved in the vesicle trafficking events. The hypothesis designates voltage-gated Ca²⁺ channels and Ca²⁺-gated K⁺ channels to ribs and pegs that are connected to macromolecules that span the presynaptic membrane at the active zone. SNARE proteins (Syntaxin, SNAP25, and Synaptobrevin), SNARE-interacting proteins Synaptotagmin, Munc13, Munc18, Complexin, and NSF are designated to ribs and/or pins. Rab3A and Rabphillin-3A are designated to top-masts and/or booms and/or spars. RIM, Bassoon, and Piccolo are designated to beams, steps, masts, ribs, spars, booms, and top-masts. Spectrin is designated to beams. Lastly, the luminal portions of SV2 are thought to form the bulk of the observed synaptic vesicle luminal filaments. The goal here is to help direct future studies that aim to bridge Active Zone Material structure, biochemistry, and function to ultimately determine how it regulates the trafficking events <i>in vivo</i> that lead to neurotransmitter secretion.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"798225"},"PeriodicalIF":3.7,"publicationDate":"2022-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39852348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"(M)Unc13s in Active Zone Diversity: A <i>Drosophila</i> Perspective.","authors":"Chengji Piao,&nbsp;Stephan J Sigrist","doi":"10.3389/fnsyn.2021.798204","DOIUrl":"https://doi.org/10.3389/fnsyn.2021.798204","url":null,"abstract":"<p><p>The so-called active zones at pre-synaptic terminals are the ultimate filtering devices, which couple between action potential frequency and shape, and the information transferred to the post-synaptic neurons, finally tuning behaviors. Within active zones, the release of the synaptic vesicle operates from specialized \"release sites.\" The (M)Unc13 class of proteins is meant to define release sites topologically and biochemically, and diversity between Unc13-type release factor isoforms is suspected to steer diversity at active zones. The two major Unc13-type isoforms, namely, Unc13A and Unc13B, have recently been described from the molecular to the behavioral level, exploiting <i>Drosophila</i> being uniquely suited to causally link between these levels. The exact nanoscale distribution of voltage-gated Ca²⁺ channels relative to release sites (\"coupling\") at pre-synaptic active zones fundamentally steers the release of the synaptic vesicle. Unc13A and B were found to be either tightly or loosely coupled across <i>Drosophila</i> synapses. In this review, we reported recent findings on diverse aspects of <i>Drosophila</i> Unc13A and B, importantly, their nano-topological distribution at active zones and their roles in release site generation, active zone assembly, and pre-synaptic homeostatic plasticity. We compared their stoichiometric composition at different synapse types, reviewing the correlation between nanoscale distribution of these two isoforms and release physiology and, finally, discuss how isoform-specific release components might drive the functional heterogeneity of synapses and encode discrete behavior.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"798204"},"PeriodicalIF":3.7,"publicationDate":"2022-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39835304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metaplasticity framework for cross-modal synaptic plasticity in adults.","authors":"Hey-Kyoung Lee","doi":"10.3389/fnsyn.2022.1087042","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.1087042","url":null,"abstract":"<p><p>Sensory loss leads to widespread adaptation of neural circuits to mediate cross-modal plasticity, which allows the organism to better utilize the remaining senses to guide behavior. While cross-modal interactions are often thought to engage multisensory areas, cross-modal plasticity is often prominently observed at the level of the primary sensory cortices. One dramatic example is from functional imaging studies in humans where cross-modal recruitment of the deprived primary sensory cortex has been observed during the processing of the spared senses. In addition, loss of a sensory modality can lead to enhancement and refinement of the spared senses, some of which have been attributed to compensatory plasticity of the spared sensory cortices. Cross-modal plasticity is not restricted to early sensory loss but is also observed in adults, which suggests that it engages or enables plasticity mechanisms available in the adult cortical circuit. Because adult cross-modal plasticity is observed without gross anatomical connectivity changes, it is thought to occur mainly through functional plasticity of pre-existing circuits. The underlying cellular and molecular mechanisms involve activity-dependent homeostatic and Hebbian mechanisms. A particularly attractive mechanism is the sliding threshold metaplasticity model because it innately allows neurons to dynamically optimize their feature selectivity. In this mini review, I will summarize the cellular and molecular mechanisms that mediate cross-modal plasticity in the adult primary sensory cortices and evaluate the metaplasticity model as an effective framework to understand the underlying mechanisms.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 ","pages":"1087042"},"PeriodicalIF":3.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9853192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9819103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heightened sympathetic neuron activity and altered cardiomyocyte properties in spontaneously hypertensive rats during the postnatal period.","authors":"Marián Haburčák,&nbsp;Joshua Harrison,&nbsp;Melda M Buyukozturk,&nbsp;Surbhi Sona,&nbsp;Samuel Bates,&nbsp;Susan J Birren","doi":"10.3389/fnsyn.2022.995474","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.995474","url":null,"abstract":"<p><p>The Spontaneously Hypertensive Rat (SHR) has increased sympathetic drive to the periphery that precedes and contributes to the development of high blood pressure, making it a useful model for the study of neurogenic hypertension. Comparisons to the normotensive Wistar Kyoto (WKY) rat have demonstrated altered active and intrinsic properties of SHR sympathetic neurons shortly before the onset of hypertension. Here we examine the structural and functional plasticity of postnatal SHR and WKY sympathetic neurons cultured alone or co-cultured with cardiomyocytes under conditions of limited extrinsic signaling. SHR neurons have an increased number of structural synaptic sites compared to age-matched WKY neurons, measured by the co-localization of presynaptic vesicular acetylcholine transporter and postsynaptic shank proteins. Whole cell recordings show that SHR neurons have a higher synaptic charge than WKY neurons, demonstrating that the increase in synaptic sites is associated with increased synaptic transmission. Differences in synaptic properties are not associated with altered firing rates between postnatal WKY and SHR neurons and are not influenced by interactions with target cardiomyocytes from either strain. Both SHR and WKY neurons show tonic firing patterns in our cultures, which are depleted of non-neuronal ganglionic cells and provide limited neurotrophic signaling. This suggests that the normal mature, phasic firing of sympathetic neurons requires extrinsic signaling, with potentially differential responses in the prehypertensive SHR, which have been reported to maintain tonic firing at later developmental stages. While cardiomyocytes do not drive neuronal differences in our cultures, SHR cardiomyocytes display decreased hypertrophy compared to WKY cells and altered responses to co-cultured sympathetic neurons. These experiments suggest that altered signaling in SHR neurons and cardiomyocytes contributes to changes in the cardiac-sympathetic circuit in prehypertensive rats as early as the postnatal period.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 ","pages":"995474"},"PeriodicalIF":3.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9561918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10671809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The calcineurin regulator Sarah enables distinct forms of homeostatic plasticity at the <i>Drosophila</i> neuromuscular junction.","authors":"Noah S Armstrong,&nbsp;C Andrew Frank","doi":"10.3389/fnsyn.2022.1033743","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.1033743","url":null,"abstract":"<p><p><b>Introduction:</b> The ability of synapses to maintain physiological levels of evoked neurotransmission is essential for neuronal stability. A variety of perturbations can disrupt neurotransmission, but synapses often compensate for disruptions and work to stabilize activity levels, using forms of homeostatic synaptic plasticity. Presynaptic homeostatic potentiation (PHP) is one such mechanism. PHP is expressed at the <i>Drosophila melanogaster</i> larval neuromuscular junction (NMJ) synapse, as well as other NMJs. In PHP, presynaptic neurotransmitter release increases to offset the effects of impairing muscle transmitter receptors. Prior <i>Drosophila</i> work has studied PHP using different ways to perturb muscle receptor function-either acutely (using pharmacology) or chronically (using genetics). Some of our prior data suggested that cytoplasmic calcium signaling was important for expression of PHP after genetic impairment of glutamate receptors. Here we followed up on that observation. <b>Methods:</b> We used a combination of transgenic <i>Drosophila</i> RNA interference and overexpression lines, along with NMJ electrophysiology, synapse imaging, and pharmacology to test if regulators of the calcium/calmodulin-dependent protein phosphatase calcineurin are necessary for the normal expression of PHP. <b>Results:</b> We found that either pre- or postsynaptic dysregulation of a <i>Drosophila</i> gene regulating calcineurin, <i>sarah</i> (<i>sra</i>), blocks PHP. Tissue-specific manipulations showed that either increases or decreases in <i>sra</i> expression are detrimental to PHP. Additionally, pharmacologically and genetically induced forms of expression of PHP are functionally separable depending entirely upon which <i>sra</i> genetic manipulation is used. Surprisingly, dual-tissue pre- and postsynaptic <i>sra</i> knockdown or overexpression can ameliorate PHP blocks revealed in single-tissue experiments. Pharmacological and genetic inhibition of calcineurin corroborated this latter finding. <b>Discussion:</b> Our results suggest tight calcineurin regulation is needed across multiple tissue types to stabilize peripheral synaptic outputs.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 ","pages":"1033743"},"PeriodicalIF":3.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9846150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9536951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patch-to-Seq and Transcriptomic Analyses Yield Molecular Markers of Functionally Distinct Brainstem Serotonin Neurons.","authors":"Gary C Mouradian,&nbsp;Pengyuan Liu,&nbsp;Pablo Nakagawa,&nbsp;Erin Duffy,&nbsp;Javier Gomez Vargas,&nbsp;Kirthikaa Balapattabi,&nbsp;Justin L Grobe,&nbsp;Curt D Sigmund,&nbsp;Matthew R Hodges","doi":"10.3389/fnsyn.2022.910820","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.910820","url":null,"abstract":"<p><p>Acute regulation of CO₂ and pH homeostasis requires sensory feedback from peripheral (carotid body) and central (central) CO₂/pH sensitive cells - so called respiratory chemoreceptors. Subsets of brainstem serotonin (5-HT) neurons in the medullary raphe are CO₂ sensitive or insensitive based on differences in embryonic origin, suggesting these functionally distinct subpopulations may have unique transcriptional profiles. Here, we used Patch-to-Seq to determine if the CO₂ responses in brainstem 5-HT neurons could be correlated to unique transcriptional profiles and/or unique molecular markers and pathways. First, firing rate changes with hypercapnic acidosis were measured in fluorescently labeled 5-HT neurons in acute brainstem slices from transgenic, Dahl SS (SSMcwi) rats expressing T2/ePet-eGFP transgene in Pet-1 expressing (serotonin) neurons (SS ^{<i>ePet</i>1-eGFP} rats). Subsequently, the transcriptomic and pathway profiles of CO₂ sensitive and insensitive 5-HT neurons were determined and compared by single cell RNA (scRNAseq) and bioinformatic analyses. Low baseline firing rates were a distinguishing feature of CO₂ sensitive 5-HT neurons. scRNAseq of these recorded neurons revealed 166 differentially expressed genes among CO₂ sensitive and insensitive 5-HT neurons. Pathway analyses yielded novel predicted upstream regulators, including the transcription factor <i>Egr2</i> and <i>Leptin</i>. Additional bioinformatic analyses identified 6 candidate gene markers of CO₂ sensitive 5-HT neurons, and 2 selected candidate genes (<i>CD46</i> and <i>Iba57</i>) were both expressed in 5-HT neurons determined via <i>in situ</i> mRNA hybridization. Together, these data provide novel insights into the transcriptional control of cellular chemoreception and provide unbiased candidate gene markers of CO₂ sensitive 5-HT neurons. Methodologically, these data highlight the utility of the patch-to-seq technique in enabling the linkage of gene expression to specific functions, like CO₂ chemoreception, in a single cell to identify potential mechanisms underlying functional differences in otherwise similar cell types.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 ","pages":"910820"},"PeriodicalIF":3.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9542397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>GRIN2B</i>-related neurodevelopmental disorder: current understanding of pathophysiological mechanisms.","authors":"Shasta L Sabo,&nbsp;Jessica M Lahr,&nbsp;Madelyn Offer,&nbsp;Anika LA Weekes,&nbsp;Michael P Sceniak","doi":"10.3389/fnsyn.2022.1090865","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.1090865","url":null,"abstract":"<p><p><i>The GRIN2B</i>-related neurodevelopmental disorder is a rare disease caused by mutations in the <i>GRIN2B</i> gene, which encodes the GluN2B subunit of NMDA receptors. Most individuals with <i>GRIN2B</i>-related neurodevelopmental disorder present with intellectual disability and developmental delay. Motor impairments, autism spectrum disorder, and epilepsy are also common. A large number of pathogenic <i>de novo</i> mutations have been identified in <i>GRIN2B</i>. However, it is not yet known how these variants lead to the clinical symptoms of the disease. Recent research has begun to address this issue. Here, we describe key experimental approaches that have been used to better understand the pathophysiology of this disease. We discuss the impact of several distinct pathogenic <i>GRIN2B</i> variants on NMDA receptor properties. We then critically review pivotal studies examining the synaptic and neurodevelopmental phenotypes observed when disease-associated GluN2B variants are expressed in neurons. These data provide compelling evidence that various GluN2B mutants interfere with neuronal differentiation, dendrite morphogenesis, synaptogenesis, and synaptic plasticity. Finally, we identify important open questions and considerations for future studies aimed at understanding this complex disease. Together, the existing data provide insight into the pathophysiological mechanisms that underlie <i>GRIN2B</i>-related neurodevelopmental disorder and emphasize the importance of comparing the effects of individual, disease-associated variants. Understanding the molecular, cellular and circuit phenotypes produced by a wide range of <i>GRIN2B</i> variants should lead to the identification of core neurodevelopmental phenotypes that characterize the disease and lead to its symptoms. This information could help guide the development and application of effective therapeutic strategies for treating individuals with <i>GRIN2B</i>-related neurodevelopmental disorder.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 ","pages":"1090865"},"PeriodicalIF":3.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9873235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10628596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}