Interneuron epigenomes during the critical period of cortical plasticity: Implications for schizophrenia

Neurobiol Learn Mem. 2015 Oct;124:104-10. doi: 10.1016/j.nlm.2015.03.005. Epub 2015 Apr 4.


Schizophrenia, a major psychiatric disorder defined by delusions and hallucinations, among other symptoms, often with onset in early adulthood, is potentially associated with molecular and cellular alterations in parvalbumin-expressing fast spiking interneurons and other constituents of the cortical inhibitory GABAergic circuitry. The underlying mechanisms, including the role of disease-associated risk factors operating in adolescence such as drug abuse and social stressors, remain incompletely understood. Here, we summarize emerging findings from animal models, highlighting the ability of parvalbuminergic interneurons (PVI) to induce, during the juvenile period, long-term plastic changes in prefrontal and visual cortex, thereby altering perception, cognition and behavior in the adult. Of note, molecular alterations in PVI from subjects with schizophrenia, including downregulated expression of a subset of GABAergic genes, have also been found in juvenile stress models of the disorder. Some of the transcriptional alterations observed in schizophrenia postmortem brain could be linked to changes in the epigenetic architecture of GABAergic gene promoters, including dysregulated DNA methylation, histone modification patterns and disruption of promoter-enhancer interactions at site of chromosomal loop formations. Therefore, we predict that, in the not-to-distant future, PVI- and other cell-type specific epigenomic mappings in the animal model and human brain will provide novel insights into the pathophysiology of schizophrenia and related psychotic diseases, including the role of cortical GABAergic circuitry in shaping long-term plasticity and cognitive function of the cerebral cortex.

Keywords: Cortical plasticity; Critical period; Epigenome; Parvalbuminergic interneuron; Schizophrenia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cerebral Cortex / growth & development*
  • Cerebral Cortex / physiopathology
  • DNA Methylation
  • Disease Models, Animal
  • Epigenesis, Genetic*
  • GABAergic Neurons / physiology*
  • Glutamate Decarboxylase / genetics
  • Humans
  • Interneurons / physiology*
  • Neuronal Plasticity*
  • Parvalbumins / metabolism
  • Prefrontal Cortex / growth & development
  • Prefrontal Cortex / physiopathology
  • Schizophrenia / genetics*
  • Schizophrenia / physiopathology*
  • Time Factors
  • Visual Cortex / growth & development
  • Visual Cortex / physiopathology


  • Parvalbumins
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1