Altered Cortical Ensembles in Mouse Models of Schizophrenia

Neuron. 2017 Apr 5;94(1):153-167.e8. doi: 10.1016/j.neuron.2017.03.019.


In schizophrenia, brain-wide alterations have been identified at the molecular and cellular levels, yet how these phenomena affect cortical circuit activity remains unclear. We studied two mouse models of schizophrenia-relevant disease processes: chronic ketamine (KET) administration and Df(16)A+/-, modeling 22q11.2 microdeletions, a genetic variant highly penetrant for schizophrenia. Local field potential recordings in visual cortex confirmed gamma-band abnormalities similar to patient studies. Two-photon calcium imaging of local cortical populations revealed in both models a deficit in the reliability of neuronal coactivity patterns (ensembles), which was not a simple consequence of altered single-neuron activity. This effect was present in ongoing and sensory-evoked activity and was not replicated by acute ketamine administration or pharmacogenetic parvalbumin-interneuron suppression. These results are consistent with the hypothesis that schizophrenia is an "attractor" disease and demonstrate that degraded neuronal ensembles are a common consequence of diverse genetic, cellular, and synaptic alterations seen in chronic schizophrenia.

Keywords: 22q11.2; attractor; calcium imaging; gamma oscillations; interneuron; ketamine; parvalbumin; schizophrenia; two-photon; visual cortex.

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Brain
  • DiGeorge Syndrome / genetics
  • DiGeorge Syndrome / psychology
  • Disease Models, Animal*
  • Evoked Potentials, Visual / physiology*
  • Excitatory Amino Acid Antagonists / toxicity
  • Gamma Rhythm / physiology*
  • Interneurons / physiology
  • Ketamine / toxicity
  • Mice
  • Mice, Knockout
  • Neural Inhibition / physiology
  • Neurons / physiology*
  • Parvalbumins
  • Schizophrenia / chemically induced
  • Schizophrenia / genetics
  • Schizophrenia / physiopathology*
  • Visual Cortex / physiopathology*


  • Excitatory Amino Acid Antagonists
  • Parvalbumins
  • Ketamine