TY - JOUR T1 - Parvalbumin Interneuron Dysfunction in a Thalamo-Prefrontal Cortical Circuit in <em>Disc1</em> Locus Impairment Mice JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0496-19.2020 VL - 7 IS - 2 SP - ENEURO.0496-19.2020 AU - Kristen Delevich AU - Hanna Jaaro-Peled AU - Mario Penzo AU - Akira Sawa AU - Bo Li Y1 - 2020/03/01 UR - http://www.eneuro.org/content/7/2/ENEURO.0496-19.2020.abstract N2 - Altered cortical excitation-inhibition (E-I) balance resulting from abnormal parvalbumin interneuron (PV IN) function is a proposed pathophysiological mechanism of schizophrenia and other major psychiatric disorders. Preclinical studies have indicated that disrupted-in-schizophrenia-1 (Disc1) is a useful molecular lead to address the biology of prefrontal cortex (PFC)-dependent cognition and PV IN function. To date, PFC inhibitory circuit function has not been investigated in depth in Disc1 locus impairment (LI) mouse models. Therefore, we used a Disc1 LI mouse model to investigate E-I balance in medial PFC (mPFC) circuits. We found that inhibition onto layer 2/3 excitatory pyramidal neurons in the mPFC was significantly reduced in Disc1 LI mice. This reduced inhibition was accompanied by decreased GABA release from local PV, but not somatostatin (SOM) INs, and by impaired feedforward inhibition (FFI) in the mediodorsal thalamus (MD) to mPFC circuit. Our mechanistic findings of abnormal PV IN function in a Disc1 LI model provide insight into biology that may be relevant to neuropsychiatric disorders including schizophrenia. ER -