p140Cap Regulates GABAergic Synaptogenesis and Development of Hippocampal Inhibitory Circuits

Isabella Russo, Daniela Gavello, Elisabetta Menna, David Vandael, Carola Veglia, Noemi Morello, Irene Corradini, Elisa Focchi, Annalisa Alfieri, Costanza Angelini, Federico Tommaso Bianchi, Alessandro Morellato, Andrea Marcantoni, Marco Sassoè-Pognetto, Matteo Maria Ottaviani, Latefa Yekhlef, Maurizio Giustetto, Stefano Taverna, Valentina Carabelli, Michela MatteoliEmilio Carbone, Emilia Turco, Paola Defilippi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1-15
Number of pages15
JournalCerebral cortex (New York, N.Y. : 1991)
DOIs
Publication statusE-pub ahead of print - Nov 17 2017

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