Parvalbumin interneuron dysfunction in a thalamo-prefrontal cortical circuit in disc1 locus impairment mice

Kristen Delevich, Hanna Jaaro-Peled, Mario Penzo, Akira Sawa, Bo Li

Research output: Contribution to journalArticlepeer-review

Abstract

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 ad-dress 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.

Original languageEnglish (US)
Article numberENEURO.0496-19.2020
JournaleNeuro
Volume7
Issue number2
DOIs
StatePublished - 2020

Keywords

  • Disrupted-in-schizophrenia-1
  • Feedforward inhibition
  • Mediodorsal thalamus
  • Parvalbumin interneur-ons
  • Prefrontal cortex

ASJC Scopus subject areas

  • Neuroscience(all)

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