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
Last
2019-01-01

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.
2019
29
1
91
105
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
File in questo prodotto:
File Dimensione Formato  
Russo 2017 bhx306-1.pdf

Accesso riservato

Descrizione: PDF Articolo
Tipo di file: PDF EDITORIALE
Dimensione 1.12 MB
Formato Adobe PDF
1.12 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Russo-2019-p140Cap Regulates GABAergic Synapto.pdf

Accesso riservato

Tipo di file: PDF EDITORIALE
Dimensione 1.12 MB
Formato Adobe PDF
1.12 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1660509
Citazioni
  • ???jsp.display-item.citation.pmc??? 6
  • Scopus 11
  • ???jsp.display-item.citation.isi??? 11
social impact