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

Altered Cortical Ensembles in Mouse Models of Schizophrenia.

Author information

1
Neurotechnology Center, Department of Biological Sciences, Columbia University, New York, NY 10027, USA. Electronic address: jph2164@columbia.edu.
2
Neurotechnology Center, Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
3
Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA; Department of Neuroscience, Columbia University, New York, NY 10032, USA.
4
Neurotechnology Center, Department of Biological Sciences, Columbia University, New York, NY 10027, USA; Department of Neuroscience, Columbia University, New York, NY 10032, USA.

Abstract

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

PMID:
28384469
PMCID:
PMC5394986
DOI:
10.1016/j.neuron.2017.03.019
[Indexed for MEDLINE]
Free PMC Article

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