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.

p140Cap Regulates GABAergic Synaptogenesis and Development of Hippocampal Inhibitory Circuits

Russo, Isabella;Gavello, Daniela;Vandael, David;VEGLIA, CAROLA;Morello, Noemi;Alfieri, Annalisa;Angelini, Costanza;Bianchi, Federico Tommaso;Morellato, Alessandro;Marcantoni, Andrea;Sassoè-Pognetto, Marco;Ottaviani, Matteo Maria;Giustetto, Maurizio;Carabelli, Valentina;Carbone, Emilio;Turco, Emilia;Defilippi, Paola
2019

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.
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https://academic.oup.com/cercor/advance-article/doi/10.1093/cercor/bhx306/4637601
https://iris.unito.it/handle/2318/1660509
GABAergic neuron development; GABAergic neurotransmission; GABAergic synaptogenesis; p140Cap
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
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