p140Cap Regulates GABAergic Synaptogenesis and Development of Hippocampal Inhibitory Circuits
| Autor: | Maurizio Giustetto, Stefano Taverna, Isabella Russo, Andrea Marcantoni, David Vandael, Alessandro Morellato, Emilia Turco, Emilio Carbone, Carola Veglia, Matteo Maria Ottaviani, F. Bianchi, Daniela Gavello, Marco Sassoè-Pognetto, Elisa Focchi, Valentina Carabelli, Michela Matteoli, Noemi Morello, Latefa Yekhlef, Elisabetta Menna, Costanza Angelini, Paola Defilippi, Irene Corradini, Annalisa Alfieri |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Cognitive Neuroscience
Synaptogenesis Mice Transgenic Hippocampal formation Inhibitory postsynaptic potential Hippocampus 050105 experimental psychology GABAergic neuron development GABAergic neurotransmission GABAergic synaptogenesis p140Cap Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Postsynaptic potential Animals 0501 psychology and cognitive sciences GABAergic Neurons Cells Cultured Mice Knockout biology Chemistry GABAA receptor 05 social sciences Neural Inhibition Mice Inbred C57BL Inhibitory Postsynaptic Potentials nervous system Synapses biology.protein Excitatory postsynaptic potential GABAergic Nerve Net Carrier Proteins Neuroscience 030217 neurology & neurosurgery Parvalbumin |
| Popis: | The neuronal scaffold protein p140Cap was investigated during hippocampal network formation. p140Cap is present in presynaptic GABAergic terminals and its genetic depletion results in a marked alteration of inhibitory synaptic activity. p140Cap-/- cultured neurons display higher frequency of miniature inhibitory postsynaptic currents (mIPSCs) with no changes of their mean amplitude. Consistent with a potential presynaptic alteration of basal GABA release, p140Cap-/- neurons exhibit a larger synaptic vesicle readily releasable pool, without any variation of single GABAA receptor unitary currents and number of postsynaptic channels. Furthermore, p140Cap-/- neurons show a premature and enhanced network synchronization and appear more susceptible to 4-aminopyridine-induced seizures in vitro and to kainate-induced seizures in vivo. The hippocampus of p140Cap-/- mice showed a significant increase in the number of both inhibitory synapses and of parvalbumin- and somatostatin-expressing interneurons. Specific deletion of p140Cap in forebrain interneurons resulted in increased susceptibility to in vitro epileptic events and increased inhibitory synaptogenesis, comparable to those observed in p140Cap-/- mice. Altogether, our data demonstrate that p140Cap finely tunes inhibitory synaptogenesis and GABAergic neurotransmission, thus regulating the establishment and maintenance of the proper hippocampal excitatory/inhibitory balance. |
| Databáze: | OpenAIRE |
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