Frontiers in Synaptic Neuroscience最新文献

{"title":"Neurexins and their ligands at inhibitory synapses.","authors":"Emma E Boxer, Jason Aoto","doi":"10.3389/fnsyn.2022.1087238","DOIUrl":"10.3389/fnsyn.2022.1087238","url":null,"abstract":"<p><p>Since the discovery of neurexins (Nrxns) as essential and evolutionarily conserved synaptic adhesion molecules, focus has largely centered on their functional contributions to glutamatergic synapses. Recently, significant advances to our understanding of neurexin function at GABAergic synapses have revealed that neurexins can play pleiotropic roles in regulating inhibitory synapse maintenance and function in a brain-region and synapse-specific manner. GABAergic neurons are incredibly diverse, exhibiting distinct synaptic properties, sites of innervation, neuromodulation, and plasticity. Different classes of GABAergic neurons often express distinct repertoires of Nrxn isoforms that exhibit differential alternative exon usage. Further, Nrxn ligands can be differentially expressed and can display synapse-specific localization patterns, which may contribute to the formation of a complex <i>trans</i>-synaptic molecular code that establishes the properties of inhibitory synapse function and properties of local circuitry. In this review, we will discuss how Nrxns and their ligands sculpt synaptic inhibition in a brain-region, cell-type and synapse-specific manner.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 ","pages":"1087238"},"PeriodicalIF":2.8,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9812575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10512814","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":"Effects of the clathrin inhibitor Pitstop-2 on synaptic vesicle recycling at a central synapse <i>in vivo</i>.","authors":"Alp Paksoy,&nbsp;Simone Hoppe,&nbsp;Yvette Dörflinger,&nbsp;Heinz Horstmann,&nbsp;Kurt Sätzler,&nbsp;Christoph Körber","doi":"10.3389/fnsyn.2022.1056308","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.1056308","url":null,"abstract":"<p><p>Four modes of endocytosis and subsequent synaptic vesicle (SV) recycling have been described at the presynapse to ensure the availability of SVs for synaptic release. However, it is unclear to what extend these modes operate under physiological activity patterns <i>in vivo</i>. The coat protein clathrin can regenerate SVs either directly from the plasma membrane (PM) via clathrin-mediated endocytosis (CME), or indirectly from synaptic endosomes by SV budding. Here, we examined the role of clathrin in SV recycling under physiological conditions by applying the clathrin inhibitor Pitstop-2 to the calyx of Held, a synapse optimized for high frequency synaptic transmission in the auditory brainstem, <i>in vivo.</i> The effects of clathrin-inhibition on SV recycling were investigated by serial sectioning scanning electron microscopy (S³EM) and 3D reconstructions of endocytic structures labeled by the endocytosis marker horseradish peroxidase (HRP). We observed large endosomal compartments as well as HRP-filled, black SVs (bSVs) that have been recently recycled. The application of Pitstop-2 led to reduced bSV but not large endosome density, increased volumes of large endosomes and shifts in the localization of both types of endocytic compartments within the synapse. These changes after perturbation of clathrin function suggest that clathrin plays a role in SV recycling from both, the PM and large endosomes, under physiological activity patterns, <i>in vivo</i>.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"1056308"},"PeriodicalIF":3.7,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9714552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35346358","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":"Serotonin as a volume transmission signal in the \"simple nervous system\" of mollusks: From axonal guidance to behavioral orchestration.","authors":"Elena E Voronezhskaya","doi":"10.3389/fnsyn.2022.1024778","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.1024778","url":null,"abstract":"COPYRIGHT © 2022 Voronezhskaya. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Serotonin as a volume transmission signal in the “simple nervous system” of mollusks: From axonal guidance to behavioral orchestration","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"1024778"},"PeriodicalIF":3.7,"publicationDate":"2022-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9679287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40494184","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":"Membrane lipid rafts are required for AMPA receptor tyrosine phosphorylation.","authors":"Takashi Hayashi","doi":"10.3389/fnsyn.2022.921772","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.921772","url":null,"abstract":"<p><p>Membrane lipid rafts are sphingolipids and cholesterol-enriched membrane microdomains, which form a center for the interaction or assembly of palmitoylated signaling molecules, including Src family non-receptor type protein tyrosine kinases. Lipid rafts abundantly exist in neurons and function in the maintenance of synapses. Excitatory synaptic strength is largely controlled by the surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors in the mammalian brain. AMPA receptor endocytosis from the synaptic surface is regulated by phosphorylation of the GluA2 subunit at tyrosine 876 by Src family kinases. Here, I revealed that tyrosine phosphorylated GluA2 is concentrated in the lipid rafts fraction. Furthermore, stimulation-induced upregulation of GluA2 tyrosine phosphorylation is disrupted by the treatment of neurons with a cholesterol-depleting compound, filipin III. These results indicate the importance of lipid rafts as enzymatic reactive sites for AMPA receptor tyrosine phosphorylation and subsequent AMPA receptor internalization from the synaptic surface.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"921772"},"PeriodicalIF":3.7,"publicationDate":"2022-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9662747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40691335","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":"Palmitoylation of A-kinase anchoring protein 79/150 modulates its nanoscale organization, trafficking, and mobility in postsynaptic spines.","authors":"Xiaobing Chen, Kevin C Crosby, Austin Feng, Alicia M Purkey, Maria A Aronova, Christine A Winters, Virginia T Crocker, Richard D Leapman, Thomas S Reese, Mark L Dell'Acqua","doi":"10.3389/fnsyn.2022.1004154","DOIUrl":"10.3389/fnsyn.2022.1004154","url":null,"abstract":"<p><p>A-kinase anchoring protein 79-human/150-rodent (AKAP79/150) organizes signaling proteins to control synaptic plasticity. AKAP79/150 associates with the plasma membrane and endosomes through its N-terminal domain that contains three polybasic regions and two Cys residues that are reversibly palmitoylated. Mutations abolishing palmitoylation (AKAP79/150 CS) reduce its endosomal localization and association with the postsynaptic density (PSD). Here we combined advanced light and electron microscopy (EM) to characterize the effects of AKAP79/150 palmitoylation on its postsynaptic nanoscale organization, trafficking, and mobility in hippocampal neurons. Immunogold EM revealed prominent extrasynaptic membrane AKAP150 labeling with less labeling at the PSD. The label was at greater distances from the spine membrane for AKAP150 CS than WT in the PSD but not in extra-synaptic locations. Immunogold EM of GFP-tagged AKAP79 WT showed that AKAP79 adopts a vertical, extended conformation at the PSD with its N-terminus at the membrane, in contrast to extrasynaptic locations where it adopts a compact or open configurations of its N- and C-termini with parallel orientation to the membrane. In contrast, GFP-tagged AKAP79 CS was displaced from the PSD coincident with disruption of its vertical orientation, while proximity and orientation with respect to the extra-synaptic membrane was less impacted. Single-molecule localization microscopy (SMLM) revealed a heterogeneous distribution of AKAP150 with distinct high-density, nano-scale regions (HDRs) overlapping the PSD but more prominently located in the extrasynaptic membrane for WT and the CS mutant. Thick section scanning transmission electron microscopy (STEM) tomography revealed AKAP150 immunogold clusters similar in size to HDRs seen by SMLM and more AKAP150 labeled endosomes in spines for WT than for CS, consistent with the requirement for AKAP palmitoylation in endosomal trafficking. Hidden Markov modeling of single molecule tracking data revealed a bound/immobile fraction and two mobile fractions for AKAP79 in spines, with the CS mutant having shorter dwell times and faster transition rates between states than WT, suggesting that palmitoylation stabilizes individual AKAP molecules in various spine subpopulations. These data demonstrate that palmitoylation fine tunes the nanoscale localization, mobility, and trafficking of AKAP79/150 in dendritic spines, which might have profound effects on its regulation of synaptic plasticity.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"1004154"},"PeriodicalIF":2.8,"publicationDate":"2022-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9521714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40388390","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":"Molecular mechanisms of synaptogenesis.","authors":"Cai Qi,&nbsp;Li-Da Luo,&nbsp;Irena Feng,&nbsp;Shaojie Ma","doi":"10.3389/fnsyn.2022.939793","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.939793","url":null,"abstract":"<p><p>Synapses are the basic units for information processing and storage in the nervous system. It is only when the synaptic connection is established, that it becomes meaningful to discuss the structure and function of a circuit. In humans, our unparalleled cognitive abilities are correlated with an increase in the number of synapses. Additionally, genes involved in synaptogenesis are also frequently associated with neurological or psychiatric disorders, suggesting a relationship between synaptogenesis and brain physiology and pathology. Thus, understanding the molecular mechanisms of synaptogenesis is the key to the mystery of circuit assembly and neural computation. Furthermore, it would provide therapeutic insights for the treatment of neurological and psychiatric disorders. Multiple molecular events must be precisely coordinated to generate a synapse. To understand the molecular mechanisms underlying synaptogenesis, we need to know the molecular components of synapses, how these molecular components are held together, and how the molecular networks are refined in response to neural activity to generate new synapses. Thanks to the intensive investigations in this field, our understanding of the process of synaptogenesis has progressed significantly. Here, we will review the molecular mechanisms of synaptogenesis by going over the studies on the identification of molecular components in synapses and their functions in synaptogenesis, how cell adhesion molecules connect these synaptic molecules together, and how neural activity mobilizes these molecules to generate new synapses. Finally, we will summarize the human-specific regulatory mechanisms in synaptogenesis and results from human genetics studies on synaptogenesis and brain disorders.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"939793"},"PeriodicalIF":3.7,"publicationDate":"2022-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9513053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40384995","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 plasticity of cardiac sympathetic nerves and its clinical implication in cardiovascular disease.","authors":"Hideaki Kanazawa,&nbsp;Keiichi Fukuda","doi":"10.3389/fnsyn.2022.960606","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.960606","url":null,"abstract":"<p><p>The heart is electrically and mechanically controlled by the autonomic nervous system, which consists of both the sympathetic and parasympathetic systems. It has been considered that the sympathetic and parasympathetic nerves regulate the cardiomyocytes' performance independently; however, recent molecular biology approaches have provided a new concept to our understanding of the mechanisms controlling the diseased heart through the plasticity of the autonomic nervous system. Studies have found that cardiac sympathetic nerve fibers in hypertrophic ventricles strongly express an immature neuron marker and simultaneously cause deterioration of neuronal cellular function. This phenomenon was explained by the rejuvenation of cardiac sympathetic nerves. Moreover, heart failure and myocardial infarction have been shown to cause cholinergic trans-differentiation of cardiac sympathetic nerve fibers <i>via</i> gp130-signaling cytokines secreted from the failing myocardium, affecting cardiac performance and prognosis. This phenomenon is thought to be one of the adaptations that prevent the progression of heart disease. Recently, the concept of using device-based neuromodulation therapies to attenuate sympathetic activity and increase parasympathetic (vagal) activity to treat cardiovascular disease, including heart failure, was developed. Although several promising preclinical and pilot clinical studies using these strategies have been conducted, the results of clinical efficacy vary. In this review, we summarize the current literature on the plasticity of cardiac sympathetic nerves and propose potential new therapeutic targets for heart disease.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"960606"},"PeriodicalIF":3.7,"publicationDate":"2022-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9500163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33485457","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":"Killer or helper? The mechanism underlying the role of adenylate activated kinase in sound conditioning.","authors":"Rui Zhao,&nbsp;Changhong Ma,&nbsp;Minjun Wang,&nbsp;Xinxin Li,&nbsp;Wei Liu,&nbsp;Lin Shi,&nbsp;Ning Yu","doi":"10.3389/fnsyn.2022.940788","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.940788","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To investigate whether sound conditioning influences auditory system protection by activating adenylate activated kinase (AMPK), and if such adaption protects ribbon synapses from high-intensity noise exposure.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;CBA mice (12 weeks old) were randomly divided into four groups (&lt;i&gt;n&lt;/i&gt; = 24 mice per group): control, sound conditioning (SC), sound conditioning plus noise exposure (SC+NE), and noise exposure (NE). Hearing thresholds were assessed before testing, after sound conditioning, and 0, 3, 7, and 14 days after 110 dB noise exposure. Amplitudes and latencies of wave I at 90 dB intensity were assessed before test, after conditioning, and at 0 and 14 days after 110 dB noise exposure. One cochlea from each mouse was subjected to immunofluorescence staining to assess synapse numbers and AMPK activation, while the other cochlea was analyzed for phosphorylated adenylate activated kinase (p-AMPK) protein expression by western blot.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;There was no significant difference in auditory brainstem response (ABR) threshold between SC and control mice. The degree of hearing loss of animals in the two SC groups was significantly reduced compared to the NE group after 110 dB noise exposure. Animals in the SC group showed faster recovery to normal thresholds, and 65 dB SPL sound conditioning had a stronger auditory protection effect. After sound conditioning, the amplitude of ABR I wave in the SC group was higher than that in the control group. Immediately after noise exposure (D0), the amplitudes of ABR I wave decreased significantly in all groups; the most significant decrease was in the NE group, with amplitude in 65SC+NE group significantly higher than that in the 85SC+NE group. Wave I latency in the SC group was significantly shorter than that in the control group. At D0, latency was prolonged in the NE group compared with the control group. In contrast, there was no significant difference in latency between the 65SC+NE and 85SC+NE groups. Further, at D14, there was no significant difference between the NE and control groups, while latency remained significantly shorter in the 65SC+NE and 85SC+NE groups compared with controls. Number of ribbon synapses in SC mice did not differ significantly from that in controls. After 110 dB noise exposure, there were significantly more ribbon synapses in the SC+NE group than the NE group. Ribbon synapses of all groups were recovered 14 days after the noise exposure, while the SC group had a shorter recovery time than the non-SC groups (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). AMPK was highly activated in the SC group, and p-AMPK expression was detected; however, after 110 dB noise exposure, the strongest protein expression was detected in the NE group, followed by the SC+NE groups, and the lowest protein expression was detected in the control group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Sound conditioning animals were more noise resistant and","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"940788"},"PeriodicalIF":3.7,"publicationDate":"2022-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9490174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33485458","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":"Editorial: Quantifying and controlling the nano-architecture of neuronal synapses.","authors":"Xiaobing Chen,&nbsp;Thomas Kuner,&nbsp;Thomas A Blanpied","doi":"10.3389/fnsyn.2022.1024073","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.1024073","url":null,"abstract":"COPYRIGHT © 2022 Chen, Kuner and Blanpied. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Quantifying and controlling the nano-architecture of neuronal synapses","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"1024073"},"PeriodicalIF":3.7,"publicationDate":"2022-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9491271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33485456","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":"Synaptic determinants of cholinergic interneurons hyperactivity during parkinsonism.","authors":"Montserrat Padilla-Orozco,&nbsp;Mariana Duhne,&nbsp;Alejandra Fuentes-Serrano,&nbsp;Aidán Ortega,&nbsp;Elvira Galarraga,&nbsp;José Bargas,&nbsp;Esther Lara-González","doi":"10.3389/fnsyn.2022.945816","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.945816","url":null,"abstract":"<p><p>Parkinson's disease is a neurodegenerative ailment generated by the loss of dopamine in the basal ganglia, mainly in the striatum. The disease courses with increased striatal levels of acetylcholine, disrupting the balance among these modulatory transmitters. These modifications disturb the excitatory and inhibitory balance in the striatal circuitry, as reflected in the activity of projection striatal neurons. In addition, changes in the firing pattern of striatal tonically active interneurons during the disease, including cholinergic interneurons (CINs), are being searched. Dopamine-depleted striatal circuits exhibit pathological hyperactivity as compared to controls. One aim of this study was to show how striatal CINs contribute to this hyperactivity. A second aim was to show the contribution of extrinsic synaptic inputs to striatal CINs hyperactivity. Electrophysiological and calcium imaging recordings in Cre-mice allowed us to evaluate the activity of dozens of identified CINs with single-cell resolution in <i>ex vivo</i> brain slices. CINs show hyperactivity with bursts and silences in the dopamine-depleted striatum. We confirmed that the intrinsic differences between the activity of control and dopamine-depleted CINs are one source of their hyperactivity. We also show that a great part of this hyperactivity and firing pattern change is a product of extrinsic synaptic inputs, targeting CINs. Both glutamatergic and GABAergic inputs are essential to sustain hyperactivity. In addition, cholinergic transmission through nicotinic receptors also participates, suggesting that the joint activity of CINs drives the phenomenon; since striatal CINs express nicotinic receptors, not expressed in striatal projection neurons. Therefore, CINs hyperactivity is the result of changes in intrinsic properties and excitatory and inhibitory inputs, in addition to the modification of local circuitry due to cholinergic nicotinic transmission. We conclude that CINs are the main drivers of the pathological hyperactivity present in the striatum that is depleted of dopamine, and this is, in part, a result of extrinsic synaptic inputs. These results show that CINs may be a main therapeutic target to treat Parkinson's disease by intervening in their synaptic inputs.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"945816"},"PeriodicalIF":3.7,"publicationDate":"2022-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9485566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33478819","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}