Expression of Transcripts Selective for GABA Neuron Subpopulations across the Cortical Visuospatial Working Memory Network in the Healthy State and Schizophrenia

Cereb Cortex. 2019 Jul 22;29(8):3540-3550. doi: 10.1093/cercor/bhy227.


Visuospatial working memory (WM), which is impaired in schizophrenia, depends on a distributed network including visual, posterior parietal, and dorsolateral prefrontal cortical regions. Within each region, information processing is differentially regulated by subsets of γ-aminobutyric acid (GABA) neurons that express parvalbumin (PV), somatostatin (SST), or vasoactive intestinal peptide (VIP). In schizophrenia, WM impairments have been associated with alterations of PV and SST neurons in the dorsolateral prefrontal cortex. Here, we quantified transcripts selectively expressed in GABA neuron subsets across four cortical regions in the WM network from comparison and schizophrenia subjects. In comparison subjects, PV mRNA levels declined and SST mRNA levels increased from posterior to anterior regions, whereas VIP mRNA levels were comparable across regions except for the primary visual cortex (V1). In schizophrenia subjects, each transcript in PV and SST neurons exhibited similar alterations across all regions, whereas transcripts in VIP neurons were unaltered in any region except for V1. These findings suggest that the contribution of each GABA neuron subset to inhibitory regulation of local circuitry normally differs across cortical regions of the visuospatial WM network and that in schizophrenia alterations of PV and SST neurons are a shared feature across these regions, whereas VIP neurons are affected only in V1.

Keywords: calretinin; parvalbumin; postmortem; somatostatin; vasoactive intestinal peptide.

MeSH terms

  • Adult
  • Brain / metabolism*
  • Case-Control Studies
  • Female
  • GABAergic Neurons / metabolism*
  • Gene Expression Profiling
  • Glutamate Decarboxylase / genetics
  • Humans
  • LIM-Homeodomain Proteins / genetics
  • Male
  • Memory, Short-Term / physiology*
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Parietal Lobe / metabolism
  • Parvalbumins / genetics*
  • Potassium Channels, Voltage-Gated / genetics
  • Prefrontal Cortex / metabolism
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Receptors, Opioid, mu / genetics
  • Schizophrenia / genetics*
  • Schizophrenia / physiopathology
  • Somatostatin / genetics*
  • Spatial Processing
  • Transcription Factors / genetics
  • Vasoactive Intestinal Peptide / genetics*
  • Visual Cortex / metabolism


  • KCNS3 protein, human
  • LHX6 protein, human
  • LIM-Homeodomain Proteins
  • Nerve Tissue Proteins
  • OPRM1 protein, human
  • PVALB protein, human
  • Parvalbumins
  • Potassium Channels, Voltage-Gated
  • RNA, Messenger
  • Receptors, Opioid, mu
  • Transcription Factors
  • Vasoactive Intestinal Peptide
  • Somatostatin
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1