Parvalbumin Interneuron Dysfunction in a Thalamo-Prefrontal Cortical Circuit in Locus Impairment Mice.

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 () 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 locus impairment (LI) mouse models. Therefore, we used a 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 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 LI model provide insight into biology that may be relevant to neuropsychiatric disorders including schizophrenia.