title: Altered resonance properties of somatosensory responses in mice deficient for the schizophrenia risk gene Neuregulin 1.
abstract: To reveal the neuronal underpinnings of sensory processing deficits in patients with schizophrenia, previous studies have investigated brain activity in response to sustained sensory stimulation at various frequencies. This paradigm evoked neural activity at the stimulation frequency and harmonics thereof. During visual and auditory stimulation that elicited enhanced or 'resonant' responses in healthy controls, patients with schizophrenia displayed reduced activity. The present study sought to elucidate the cellular basis of disease-related deficits in sensory resonance properties using mice heterozygous for the schizophrenia susceptibility gene Neuregulin 1 (NRG1). We applied repetitive whisker stimulation at 1-15 Hz, a range relevant to whisking behavior in mice, and measured cellular activity in the primary somatosensory cortex. At frequencies where control mice displayed enhancements in measures of response magnitude and precision, NRG1 (+/-) mutants showed reductions. Our results demonstrate for the first time a link between a mutation of a schizophrenia risk gene and altered neuronal resonance properties in sensory cortex.
authors.affiliation: Function of Cortical Microcircuits Group, Institute for Neuroscience and Medicine, Research Centre Jülich, Leo-Brandt-Str., 52425, Jülich, Germany. c.barz@fz-juelich.de.|Department of Psychiatry, Psychotherapy and Psychosomatics, Medical School, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany. c.barz@fz-juelich.de.|Department of Neuropathology, Medical School, RWTH Aachen University, Aachen, Germany. c.barz@fz-juelich.de.|Department of Ophthalmology, Medical School, RWTH Aachen University, Aachen, Germany. c.barz@fz-juelich.de.|IZKF Aachen, Medical School, RWTH Aachen University, Aachen, Germany. c.barz@fz-juelich.de.
authors.forename: Claudia S
authors.initials: CS
authors.lastname: Barz
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UM CR18, Neuroscience Paris Seine, Paris, France.|INSERM, UMR-S 1130, Neuroscience Paris Seine, Paris, France.|CNRS, UMR 8246, Neuroscience Paris Seine, Paris, France.|Université Pierre et Marie Curie, Laboratoire Neuroscience Paris Seine, 9 quai Staint Bernard, Bat B, 5e etage, Case courrier 16, 75005, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bessaih
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, USA.|10-133 Smilow Center for Translational Research, 3400 Civic Center Boulevard, Building 421, Philadelphia, PA, 19104, USA.
authors.forename: Ted
authors.initials: T
authors.lastname: Abel
authors.affiliation: Function of Cortical Microcircuits Group, Institute for Neuroscience and Medicine, Research Centre Jülich, Leo-Brandt-Str., 52425, Jülich, Germany.|Department of Psychiatry, Psychotherapy and Psychosomatics, Medical School, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany.|Jülich Aachen Research Alliance (JARA)-Translational Brain Medicine, Aachen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Feldmeyer
authors.affiliation: Department of Neuroscience, School of Medicine, University of Pennsylvania, 215 Stemmler Hall, Philadelphia, PA, 19104-6074, USA.
authors.forename: Diego
authors.initials: D
authors.lastname: Contreras
mesh_terms: D000200:Action Potentials; D000222:Adaptation, Physiological; D000818:Animals; D005073:Evoked Potentials, Somatosensory; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020890:Neuregulin-1 / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010812:Physical Stimulation; D012559:Schizophrenia / Q000503:physiopathology*; D013003:Somatosensory Cortex / Q000502:physiology*; D055698:Touch Perception / Q000502:physiology*; D014738:Vibrissae / Q000502:physiology
chemical_list: D020890:Neuregulin-1; C490581:Nrg1 protein, mouse
keywords: Adaptation; Endophenotypes; Neuregulin 1; Resonance; Schizophrenia; Somatosensory cortex; Synchrony