Alterations in cortical interneurons and cognitive function in schizophrenia

Neurobiol Dis. 2019 Nov:131:104208. doi: 10.1016/j.nbd.2018.06.020. Epub 2018 Jun 22.

Abstract

Certain clinical features of schizophrenia, such as working memory disturbances, appear to emerge from altered gamma oscillatory activity in the prefrontal cortex (PFC). Given the essential role of GABA neurotransmission in both working memory and gamma oscillations, understanding the cellular substrate for their disturbances in schizophrenia requires evidence from in vivo neuroimaging studies, which provide a means to link markers of GABA neurotransmission to gamma oscillations and working memory, and from postmortem studies, which provide insight into GABA neurotransmission at molecular and cellular levels of resolution. Here, we review findings from both types of studies which converge on the notions that 1) inhibitory GABA signaling in the PFC, especially between parvalbumin positive GABAergic basket cells and excitatory pyramidal cells, is required for gamma oscillatory activity and working memory function; and 2) disturbances in this signaling contribute to altered gamma oscillations and working memory in schizophrenia. Because the PFC is only one node in a distributed cortical network that mediates working memory, we also review evidence of GABA abnormalities in other cortical regions in schizophrenia.

Keywords: Cognition; GABA; Interneurons; Neuroimaging; Schizophrenia; Working memory.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cerebral Cortex / physiopathology*
  • Cognition / physiology
  • GABAergic Neurons / physiology*
  • Humans
  • Interneurons / physiology*
  • Memory, Short-Term / physiology
  • Models, Neurological
  • Schizophrenia / physiopathology*
  • Synaptic Transmission / physiology*