دورية أكاديمية
MDGA2 Constrains Glutamatergic Inputs Selectively onto CA1 Pyramidal Neurons to Optimize Neural Circuits for Plasticity, Memory, and Social Behavior.
العنوان: | MDGA2 Constrains Glutamatergic Inputs Selectively onto CA1 Pyramidal Neurons to Optimize Neural Circuits for Plasticity, Memory, and Social Behavior. |
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المؤلفون: | Wang X; School of Life Sciences, Nanchang University, Nanchang, 330031, China.; Department of Neurology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310052, China., Lin D; Department of Neurology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310052, China., Jiang J; Department of Neurology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310052, China.; Department of Biology, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canada., Liu Y; School of Life Sciences, Nanchang University, Nanchang, 330031, China.; Department of Neurology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310052, China., Dong X; Department of Neurology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310052, China., Fan J; Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, 310015, China., Gong L; Department of Neurology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310052, China., Shen W; Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, 310015, China., Zeng L; Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, 310015, China., Xu T; School of Life Sciences, Nanchang University, Nanchang, 330031, China., Jiang K; Department of Neurology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310052, China. jiangke_zju@zju.edu.cn., Connor SA; Department of Biology, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canada. saconnor@yorku.ca., Xie Y; School of Life Sciences, Nanchang University, Nanchang, 330031, China. ycxie@zju.edu.cn.; Department of Neurology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310052, China. ycxie@zju.edu.cn. |
المصدر: | Neuroscience bulletin [Neurosci Bull] 2024 Jul; Vol. 40 (7), pp. 887-904. Date of Electronic Publication: 2024 Feb 06. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Springer Singapore Country of Publication: Singapore NLM ID: 101256850 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1995-8218 (Electronic) Linking ISSN: 19958218 NLM ISO Abbreviation: Neurosci Bull Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Singapore : Springer Singapore Original Publication: Beijing, China : Science Press, 2005- |
مواضيع طبية MeSH: | CA1 Region, Hippocampal*/metabolism , CA1 Region, Hippocampal*/physiology , Neuronal Plasticity*/physiology , Pyramidal Cells*/physiology , Pyramidal Cells*/metabolism , Social Behavior* , Synapses*/metabolism , Synapses*/physiology, Animals ; Male ; Mice ; Excitatory Postsynaptic Potentials/physiology ; Glutamic Acid/metabolism ; Memory/physiology ; Mice, Inbred C57BL ; Mice, Knockout |
مستخلص: | Synapse organizers are essential for the development, transmission, and plasticity of synapses. Acting as rare synapse suppressors, the MAM domain containing glycosylphosphatidylinositol anchor (MDGA) proteins contributes to synapse organization by inhibiting the formation of the synaptogenic neuroligin-neurexin complex. A previous analysis of MDGA2 mice lacking a single copy of Mdga2 revealed upregulated glutamatergic synapses and behaviors consistent with autism. However, MDGA2 is expressed in diverse cell types and is localized to both excitatory and inhibitory synapses. Differentiating the network versus cell-specific effects of MDGA2 loss-of-function requires a cell-type and brain region-selective strategy. To address this, we generated mice harboring a conditional knockout of Mdga2 restricted to CA1 pyramidal neurons. Here we report that MDGA2 suppresses the density and function of excitatory synapses selectively on pyramidal neurons in the mature hippocampus. Conditional deletion of Mdga2 in CA1 pyramidal neurons of adult mice upregulated miniature and spontaneous excitatory postsynaptic potentials, vesicular glutamate transporter 1 intensity, and neuronal excitability. These effects were limited to glutamatergic synapses as no changes were detected in miniature and spontaneous inhibitory postsynaptic potential properties or vesicular GABA transporter intensity. Functionally, evoked basal synaptic transmission and AMPAR receptor currents were enhanced at glutamatergic inputs. At a behavioral level, memory appeared to be compromised in Mdga2 cKO mice as both novel object recognition and contextual fear conditioning performance were impaired, consistent with deficits in long-term potentiation in the CA3-CA1 pathway. Social affiliation, a behavioral analog of social deficits in autism, was similarly compromised. These results demonstrate that MDGA2 confines the properties of excitatory synapses to CA1 neurons in mature hippocampal circuits, thereby optimizing this network for plasticity, cognition, and social behaviors. (© 2024. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.) |
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فهرسة مساهمة: | Keywords: Autism; CA1 pyramidal neurons; Glutamatergic inputs; MDGA2; Memory; Social behaviors; Synapse organizers; Synaptic plasticity |
المشرفين على المادة: | 3KX376GY7L (Glutamic Acid) |
تواريخ الأحداث: | Date Created: 20240206 Date Completed: 20240715 Latest Revision: 20240718 |
رمز التحديث: | 20240718 |
مُعرف محوري في PubMed: | PMC11250762 |
DOI: | 10.1007/s12264-023-01171-1 |
PMID: | 38321347 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1995-8218 |
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DOI: | 10.1007/s12264-023-01171-1 |