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Impaired synaptic plasticity in an animal model of autism exhibiting early hippocampal GABAergic-BDNF/TrkB signaling alterations.
Sgritta, Martina; Vignoli, Beatrice; Pimpinella, Domenico; Griguoli, Marilena; Santi, Spartaco; Bialowas, Andrzej; Wiera, Grzegorz; Zacchi, Paola; Malerba, Francesca; Marchetti, Cristina; Canossa, Marco; Cherubini, Enrico.
Afiliação
  • Sgritta M; European Brain Research Institute (EBRI), 00161 Rome, Italy.
  • Vignoli B; Department of Physics, University of Trento, Povo, 38123 TN, Italy.
  • Pimpinella D; European Brain Research Institute (EBRI), 00161 Rome, Italy.
  • Griguoli M; European Brain Research Institute (EBRI), 00161 Rome, Italy.
  • Santi S; Institute of Molecular Biology and Pathology, National Research Council, 00185 Rome, Italy.
  • Bialowas A; Institute of Molecular Genetics "Cavalli-Sforza", National Research Council/IRCCS, Istituto Ortopedico Rizzoli, 40136 Bologna, Italy.
  • Wiera G; Department of Neuroscience, International School for Advanced Studies (SISSA), 34136 Trieste, Italy.
  • Zacchi P; Department of Neuroscience, International School for Advanced Studies (SISSA), 34136 Trieste, Italy.
  • Malerba F; Department of Life Sciences, University of Trieste, 34128 Trieste, Italy.
  • Marchetti C; European Brain Research Institute (EBRI), 00161 Rome, Italy.
  • Canossa M; European Brain Research Institute (EBRI), 00161 Rome, Italy.
  • Cherubini E; Institute of Molecular Biology and Pathology, National Research Council, 00185 Rome, Italy.
iScience ; 26(1): 105728, 2023 Jan 20.
Article em En | MEDLINE | ID: mdl-36582822
In Neurodevelopmental Disorders, alterations of synaptic plasticity may trigger structural changes in neuronal circuits involved in cognitive functions. This hypothesis was tested in mice carrying the human R451C mutation of Nlgn3 gene (NLG3R451C KI), found in some families with autistic children. To this aim, the spike time dependent plasticity (STDP) protocol was applied to immature GABAergic Mossy Fibers (MF)-CA3 connections in hippocampal slices from NLG3R451C KI mice. These animals failed to exhibit STD-LTP, an effect that persisted in adulthood when these synapses became glutamatergic. Similar results were obtained in mice lacking the Nlgn3 gene (NLG3 KO mice), suggesting a loss of function. The loss of STD-LTP was associated with a premature shift of GABA from the depolarizing to the hyperpolarizing direction, a reduced BDNF availability and TrkB phosphorylation at potentiated synapses. These effects may constitute a general mechanism underlying cognitive deficits in those forms of Autism caused by synaptic dysfunctions.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article