P140Cap Regulates GABAergic Synaptogenesis and Development of Hippocampal Inhibitory Circuits. (17th November 2017)

• Record Type: Journal Article
• Authors: Russo, Isabella; Gavello, Daniela; Menna, Elisabetta; Vandael, David; Veglia, Carola; Morello, Noemi; Corradini, Irene; Focchi, Elisa; Alfieri, Annalisa; Angelini, Costanza; Bianchi, Federico Tommaso; Morellato, Alessandro; Marcantoni, Andrea; Sassoè-Pognetto, Marco; Ottaviani, Matteo Maria; Yekhlef, Latefa; Giustetto, Maurizio; Taverna, Stefano; Carabelli, Valentina; Matteoli, Michela; Carbone, Emilio; Turco, Emilia; Defilippi, Paola
• Is Part Of: Cerebral cortex. Volume 29:Number 1(2019)
• Page Start: 91
• Page End: 105
• Publication Date: 2017-11-17
• Subjects: p140Cap -- GABAergic synaptogenesis -- GABAergic neuron development -- GABAergic neurotransmission; Cerebral cortex -- Periodicals; Brain -- Periodicals; 612.825
• DOI: 10.1093/cercor/bhx306
• Languages: English
• ISSNs: 1047-3211

Abstract

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.