Neuroscientist最新文献

{"title":"Forthcoming Articles.","authors":"","doi":"10.1177/10738584231179065","DOIUrl":"https://doi.org/10.1177/10738584231179065","url":null,"abstract":"","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 4","pages":"388-389"},"PeriodicalIF":5.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9693805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>The Neuroscientist</i> Comments.","authors":"","doi":"10.1177/10738584231178681","DOIUrl":"https://doi.org/10.1177/10738584231178681","url":null,"abstract":"","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 4","pages":"390"},"PeriodicalIF":5.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9751710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>The Neuroscientist</i> Comments.","authors":"","doi":"10.1177/10738584231178682","DOIUrl":"https://doi.org/10.1177/10738584231178682","url":null,"abstract":"The NeuroscieNTisT commeNTs ~ The NeuroscieNTisT commeNTs~ The NeuroscieNTisT commeNTs T h e N e u r o s c ie N T is T c o m m e N T s ~ T h e N e u r o s c ie N T is T c o m m e N T s ~ T h e N e u r o s c ie N T is T c o m m e N T s ~ T h e N e u r o s c ie N T is T c o m m e N T s T h e N e u r o s c ie N T is T c o m m e N T s ~ T h e N e u r o s c ie N T is T c o m m e N T s ~ T h e N e u r o s c ie N T is T c o m m e N T s ~ T h e N e u r o s c ie N T is T c o m m e N T s A Dynamic Astrocyte Chloride Reservoir: Regulating Inhibitory Neurotransmission during Sustained Neuronal","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 4","pages":"391"},"PeriodicalIF":5.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10055025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Insights on Glutamatergic Dysfunction in Alzheimer's Disease and Therapeutic Implications.","authors":"Priyanka D Pinky,&nbsp;Jeremiah C Pfitzer,&nbsp;Jared Senfeld,&nbsp;Hao Hong,&nbsp;Subhrajit Bhattacharya,&nbsp;Vishnu Suppiramaniam,&nbsp;Irfan Qureshi,&nbsp;Miranda N Reed","doi":"10.1177/10738584211069897","DOIUrl":"https://doi.org/10.1177/10738584211069897","url":null,"abstract":"<p><p>Alzheimer's disease (AD) poses a critical public health challenge, and there is an urgent need for novel treatment options. Glutamate, the principal excitatory neurotransmitter in the human brain, plays a critical role in mediating cognitive and behavioral functions; and clinical symptoms in AD patients are highly correlated with the loss of glutamatergic synapses. In this review, we highlight how dysregulated glutamatergic mechanisms can underpin cognitive and behavioral impairments and contribute to the progression of AD via complex interactions with neuronal and neural network hyperactivity, Aβ, tau, glial dysfunction, and other disease-associated factors. We focus on the tripartite synapse, where glutamatergic neurotransmission occurs, and evidence elucidating how the tripartite synapse can be pathologically altered in AD. We also discuss promising therapeutic approaches that have the potential to rescue these deficits. These emerging data support the development of novel glutamatergic drug candidates as compelling approaches for treating AD.</p>","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 4","pages":"461-471"},"PeriodicalIF":5.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9700073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sculpting Astrocyte Diversity through Circuits and Transcription.","authors":"Yi-Ting Cheng,&nbsp;Junsung Woo,&nbsp;Benjamin Deneen","doi":"10.1177/10738584221082620","DOIUrl":"https://doi.org/10.1177/10738584221082620","url":null,"abstract":"<p><p>Astrocytes are the most abundant glial cell in the central nervous system and occupy a wide range of roles that are essential for brain function. Over the past few years, evidence has emerged that astrocytes exhibit cellular and molecular heterogeneity, raising the possibility that subsets of astrocytes are functionally distinct and that transcriptional mechanisms are involved in encoding this prospective diversity. In this review, we focus on three emerging areas of astrocyte biology: region-specific circuit regulation, molecular diversity, and transcriptional regulation. This review highlights our nascent understanding of how molecular diversity is converted to functional diversity of astrocytes through the lens of brain region-specific circuits. We articulate our understanding of how transcriptional mechanisms regulate this diversity and key areas that need further exploration to achieve the overarching goal of a functional taxonomy of astrocytes in the brain.</p>","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 4","pages":"445-460"},"PeriodicalIF":5.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9526762/pdf/nihms-1808875.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10289001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanosensitive Ion Channels, Axonal Growth, and Regeneration.","authors":"Leann Miles,&nbsp;Jackson Powell,&nbsp;Casey Kozak,&nbsp;Yuanquan Song","doi":"10.1177/10738584221088575","DOIUrl":"https://doi.org/10.1177/10738584221088575","url":null,"abstract":"<p><p>Cells sense and respond to mechanical stimuli by converting those stimuli into biological signals, a process known as mechanotransduction. Mechanotransduction is essential in diverse cellular functions, including tissue development, touch sensitivity, pain, and neuronal pathfinding. In the search for key players of mechanotransduction, several families of ion channels were identified as being mechanosensitive and were demonstrated to be activated directly by mechanical forces in both the membrane bilayer and the cytoskeleton. More recently, Piezo ion channels were discovered as a bona fide mechanosensitive ion channel, and its characterization led to a cascade of research that revealed the diverse functions of Piezo proteins and, in particular, their involvement in neuronal repair.</p>","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 4","pages":"421-444"},"PeriodicalIF":5.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9556659/pdf/nihms-1819329.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9910387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perspectives on Neuroscience and Behavior.","authors":"","doi":"10.1177/10738584231178683","DOIUrl":"https://doi.org/10.1177/10738584231178683","url":null,"abstract":"Schizophrenia (SZ) and bipolar disorder (BPD) have many common clinical features and they have shared polygenetic risks. An improved understanding of the common neurobiological pathways involved would be an important advance. Now, this has been accomplished in an outstanding study where it was found that SZ and BPD have upregulation of miR-124-3p in olfactory epithelium derived neuronal cells and postmortem prefrontal cortex, and that this was associated with shared polygenetic risks of the two disorders. In a mouse model with upregulation of miR-124-3p in the medial prefrontal cortex (mPFC) there was increased GRIA2lacking calcium-permeable AMPA receptors (AMPARs) and the mice had impaired social interaction and increased sensitivity to amphetamine. The increase in GRIA2 lacking calcium-permeable AMPARs increased the post-synaptic conductance of AMPARs and miniature excitatory postsynaptic currents (mESPC) amplitude. The selective antagonism of GRIA2-lacking calcium-permeable AMPARs by Naspm normalized the increased amplitude of mESPCs, and local infusion of Naspm into the mPFC reduced the behavioral deficits in social interaction and amphetamine sensitivity. Adeno-associated virus mediated expression of GRIA2 in mouse prefrontal cortex excitatory neurons reduced the behavioral defects (Namkung and others 2023). This article is an outstanding example of how the focus on neurobiological mechanisms underlying behavioral dimensions can improve our understanding of key biological pathways involved in the pathogenesis of behavioral abnormalities. This in turn provides new opportunities for the development of more efficacious therapeutic interventions.","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 4","pages":"392"},"PeriodicalIF":5.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10055026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influencers in the Somatosensory System: Extrinsic Control of Sensory Neuron Phenotypes.","authors":"Joriene C de Nooij","doi":"10.1177/10738584221074350","DOIUrl":"https://doi.org/10.1177/10738584221074350","url":null,"abstract":"<p><p>Somatosensory neurons in dorsal root ganglia (DRG) comprise several main subclasses: high threshold nociceptors/thermoceptors, high- and low-threshold mechanoreceptors, and proprioceptors. Recent years have seen an explosion in the identification of molecules that underlie the functional diversity of these sensory modalities. They also have begun to reveal the developmental mechanisms that channel the emergence of this subtype diversity, solidifying the importance of peripheral instructive signals. Somatic sensory neurons collectively serve numerous essential physiological and protective roles, and as such, an increased understanding of the processes that underlie the specialization of these sensory subtypes is not only biologically interesting but also clinically relevant.</p>","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 4","pages":"472-487"},"PeriodicalIF":5.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9694347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long Noncoding RNAs in CNS Myelination and Disease.","authors":"Jing Zhang,&nbsp;Menglong Guan,&nbsp;Xianyao Zhou,&nbsp;Kalen Berry,&nbsp;Xuelian He,&nbsp;Q Richard Lu","doi":"10.1177/10738584221083919","DOIUrl":"https://doi.org/10.1177/10738584221083919","url":null,"abstract":"<p><p>Myelination by oligodendrocytes is crucial for neuronal survival and function, and defects in myelination or failure in myelin repair can lead to axonal degeneration and various neurological diseases. At present, the factors that promote myelination and overcome the remyelination block in demyelinating diseases are poorly defined. Although the roles of protein-coding genes in oligodendrocyte differentiation have been extensively studied, the majority of the mammalian genome is transcribed into noncoding RNAs, and the functions of these molecules in myelination are poorly characterized. Long noncoding RNAs (lncRNAs) regulate transcription at multiple levels, providing spatiotemporal control and robustness for cell type-specific gene expression and physiological functions. lncRNAs have been shown to regulate neural cell-type specification, differentiation, and maintenance of cell identity, and dysregulation of lncRNA function has been shown to contribute to neurological diseases. In this review, we discuss recent advances in our understanding of the functions of lncRNAs in oligodendrocyte development and myelination as well their roles in neurological diseases and brain tumorigenesis. A more systematic characterization of lncRNA functional networks will be instrumental for a better understanding of CNS myelination, myelin disorders, and myelin repair.</p>","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 3","pages":"287-301"},"PeriodicalIF":5.6,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9406582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>The Neuroscientist</i> Comments.","authors":"","doi":"10.1177/10738584231166316","DOIUrl":"https://doi.org/10.1177/10738584231166316","url":null,"abstract":"Touch is an essential component of life, providing rich and detailed information on our environment that begins with activation of mechanosensitive nerve endings innervating the skin. This information is then conveyed to higher brain centers through the dorsal column nuclei of the brainstem. However, in addition to input directly from low-threshold mechanoreceptors, the dorsal column nuclei also receive signals from postsynaptic dorsal column neurons of the spinal cord, which in turn also integrate mechanoreceptor signals. In their recent study, Turecek and others (2022) sought to investigate the contribution of input from these indirect postsynaptic dorsal column neurons to the coding of touch sensation. By recording from neuron subtypes in the gracile nucleus, in combination with optogenetic tagging and antidromic stimulation, the authors showed that neurons projecting to the ventral posterolateral thalamus responded to low-frequency vibration stimuli and featured small excitatory receptive fields with large regions of surround suppression, suggesting that these neurons convey precise spatial information. In contrast, dorsal column nuclei neurons projecting to the inferior colliculus responded to a large range of vibration frequencies but with large receptive fields, indicative of a larger dynamic range but less discriminative spatial resolution. To determine the contribution of both direct (via Aβ low-threshold mechanoreceptor projections that travel through the dorsal column) and indirect (via postsynaptic dorsal column neurons of the spinal cord) inputs to the responses of dorsal column nuclei neurons, optogenetic silencing through the light-activated chloride channel was used. These experiments revealed that the indirect pathway contributes in particular to responses to very low-frequency mechanical stimulation (10 Hz) but not low-frequency (50 Hz) or high-frequency (300 Hz) vibration. By pharmacologically blocking neurotransmission of postsynaptic dorsal column neurons in the lumbar dorsal horn, a contribution of the indirect pathway to coding of sustained mechanical stimulation, specifically lowto high-intensity skin indentation, was unveiled. Thus, the indirect pathway appears critical for detection and encoding of stimulus intensities, likely through both lowand high-threshold mechanoreceptors (including Aδ and C fiber neurons) that do not project via the direct dorsal column pathway. Using light-induced activation of Calca-expressing highthreshold mechanoreceptors in a Calca-FlpE; Rosa26FSFReaChR mouse line, which exclusively signal via the indirect pathway, as well as stimulation of the direct pathway by vibration, the receptive fields of both dorsal column pathways were found to be highly correlated, suggesting reconvergence of input signals in the dorsal column nuclei to enable precise spatial and intensity representation of mechanical stimuli in single, small receptive fields. Overall, these elegant experiments demonstrate the impo","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 3","pages":"270"},"PeriodicalIF":5.6,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9410481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}