title: Altered Cortical Ensembles in Mouse Models of Schizophrenia.
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.
authors.affiliation: Neurotechnology Center, Department of Biological Sciences, Columbia University, New York, NY 10027, USA. Electronic address: jph2164@columbia.edu.
authors.forename: Jordan P
authors.initials: JP
authors.lastname: Hamm
authors.affiliation: Neurotechnology Center, Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors.forename: Darcy S
authors.initials: DS
authors.lastname: Peterka
authors.affiliation: Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA; Department of Neuroscience, Columbia University, New York, NY 10032, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Gogos
authors.affiliation: Neurotechnology Center, Department of Biological Sciences, Columbia University, New York, NY 10027, USA; Department of Neuroscience, Columbia University, New York, NY 10032, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Yuste
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001921:Brain; D004062:DiGeorge Syndrome / Q000235:genetics / Q000523:psychology; D004195:Disease Models, Animal; D005074:Evoked Potentials, Visual / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity; D065818:Gamma Rhythm / Q000502:physiology*; D007395:Interneurons / Q000502:physiology; D007649:Ketamine / Q000633:toxicity; D051379:Mice; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010320:Parvalbumins; D012559:Schizophrenia / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D014793:Visual Cortex / Q000503:physiopathology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D010320:Parvalbumins; D007649:Ketamine
keywords: 22q11.2; attractor; calcium imaging; gamma oscillations; interneuron; ketamine; parvalbumin; schizophrenia; two-photon; visual cortex