AUTHOR=Roux Sébastien , Lohof Ann , Ben-Ari Yehezkel , Poulain Bernard , Bossu Jean-Louis 

TITLE=Maturation of GABAergic Transmission in Cerebellar Purkinje Cells Is Sex Dependent and Altered in the Valproate Model of Autism

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=Volume 12 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2018.00232

DOI=10.3389/fncel.2018.00232

ISSN=1662-5102

ABSTRACT=The development of GABAergic signals includes receptor subunits reorganization, alterations of (Cl-)I levels and GABA depolarizing-excitatory/hyperpolarizing-inhibitory shift. This sequence is altered in animal models of autism stressing its relevance to disorders. Here, using cell-attached single GABAA receptor channel recordings in cerebellar Purkinje cells (PCs), we report the presence in males and females of two conductance levels (18 & 10 pS), the former being dominant in newborns and the latter in young-adults. The conductance shift like the depolarizing/excitatory to hyperpolarizing\inhibitory GABA shift occurred 4 days later in females than males. The conductance alterations like the GABA actions shifts were also delayed in valproate-treated mice. Our data support a parallel sex dependent developmental shift of  GABA conductance and chloride gradient leading to distinct excitatory/inhibitory developmental sequences in males and females. The observation that these developmental sequences are deviated in autism further stresses the importance of correct timing in the pathogenesis of disorders.