Differential impact of GABAA receptors and gephyrin post-translational modifications on layer 2/3 pyramidal neuron responsiveness in vivo
العنوان: | Differential impact of GABAA receptors and gephyrin post-translational modifications on layer 2/3 pyramidal neuron responsiveness in vivo |
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المؤلفون: | Yuan-Chen Tsai, Mohammad Hleihil, Kanako Otomo, Andrin Abegg, Anna Cavaccini, Patrizia Panzanelli, Teresa Cramer, Kim David Ferrari, Matthew J.P. Barrett, Giovanna Bosshard, Theofanis Karayannis, Bruno Weber, Jillian L. Stobart, Shiva K. Tyagarajan |
بيانات النشر: | Cold Spring Harbor Laboratory, 2020. |
سنة النشر: | 2020 |
مصطلحات موضوعية: | Scaffold protein, Gephyrin, biology, Postsynaptic potential, GABAA receptor, Conditional gene knockout, Synaptic plasticity, biology.protein, Stimulation, Inhibitory postsynaptic potential, Neuroscience |
الوصف: | A diverse set of GABAA receptors (GABAARs) enable synaptic plasticity adaptations at inhibitory postsynaptic sites in collaboration with the scaffolding protein gephyrin. Early studies helped to identify distinctions between GABAAR subtypes allocated within specific functional circuits, but their contribution to the changing dynamics of a microcircuit remains unclear. Here, using the whisker-barrel system in mouse, we assessed the contribution of specific synaptic GABAAR subtypes and gephyrin scaffolding changes to sensory processing in vivo. We monitored spontaneous and evoked Ca2+ transients in layer 2/3 pyramidal cells with the genetically encoded Ca2+ sensor RCaMP1.07. Using Gabra1 or Gabra2 global and conditional knockout mice, we uncovered that α1- and α2-GABAARs determine the sparseness of L2/3 pyramidal neuron encoding. In a cell-type dependent manner, α1-GABAARs and α2-GABAARs affected neuronal excitability and the reliability of neuronal responses after whisker stimulation. We also discerned that gephyrin with its diverse post-translational modifications (PTMs) shows preference for specific GABAAR subtype to facilitate microcircuit activity. Our results underscore the relevance of the diversity of GABAARs within a cortical microcircuit.Key pointsWhile GABAergic inhibition from interneuron subtypes regulates cortical microcircuit activity the molecular determinants have remain unclear.We demonstrate that specific-GABAA receptor subtypes contribute differentially to layer 2/3 neuronal activities in mouse barrel cortex.Importantly, we link the GABAAR contributions to the scaffolding properties of its important postsynaptic density protein gephyrin. We show that different PTMs on gephyrin determines neuronal excitability via GABAAR recruitment and modulation of inhibition within layer 2/3 neurons.Specifically, α1 and α2 subunits containing GABAA receptors, along with their scaffolding protein gephyrin determine the distribution of high, medium and low activity pyramidal neurons during sensory encoding, whereby controlling the total activity of cortical microcircuit. |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::c7fd2aff0c65ae3671aacdabde34ecc4 https://doi.org/10.1101/2020.11.25.397877 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi...........c7fd2aff0c65ae3671aacdabde34ecc4 |
قاعدة البيانات: | OpenAIRE |
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