RT Journal Article
SR Electronic
T1 Parvalbumin interneuron dysfunction in a thalamus - prefrontal cortex circuit in Disc1 deficiency mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 054759
DO 10.1101/054759
A1 Kristen Delevich
A1 Hanna Jaaro-Peled
A1 Mario Penzo
A1 Akira Sawa
A1 Bo Li
YR 2016
UL http://biorxiv.org/content/early/2016/05/21/054759.abstract
AB Two of the most consistent findings across disrupted-in-schizophrenia-1 (DISC1) mouse models are impaired working memory and reduced number or function of parvalbumin interneurons within the prefrontal cortex. While these findings suggest parvalbumin interneuron dysfunction in DISC1-related pathophysiology, to date, cortical inhibitory circuit function has not been investigated in depth in DISC1 deficiency mouse models. Here we assessed the function of a feedforward circuit between the mediodorsal thalamus (MD) and the medial prefrontal cortex (mPFC) in mice harboring a deletion in one allele of the Disc1 gene. We found that the inhibitory drive onto layer 3 pyramidal neurons in the mPFC was significantly reduced in the Disc1 deficient mice. This reduced inhibition was accompanied by decreased GABA release from local parvalbumin, but not somatostatin, inhibitory interneurons, and by impaired feedforward inhibition in the MD-mPFC circuit. Our results reveal a cellular mechanism by which deficiency in DISC1 causes neural circuit dysfunction frequently implicated in psychiatric disorders.