title: Evidence for gamma and beta sensory gating deficits as translational endophenotypes for schizophrenia.
abstract: Thorough analysis of translational endophenotypes is needed to improve therapeutic development in schizophrenia. Abnormal sensory gating, one such endophenotype, is associated with reduced expression of the α7 nicotinic receptor. However, typical gating measures such as the P50 evoked response are often low-pass filtered, and it is unclear how α7 expression affects gating at higher frequencies. Therefore, this study used time-frequency analysis to compare sensory gating at the beta and gamma frequencies between human patients and healthy controls as well as between α7 heterozygote mutant mice and wild-type. Gating of total beta (15-26Hz) and gamma (30-50Hz) power during paired clicks was assessed from mouse in vivo hippocampal CA3 recordings. Gating was also assessed in schizophrenia patients and healthy controls using electroencephalography. Relative to wild-type, α7 heterozygote mice showed impaired gating of total beta and gamma power. Similarly, relative to controls, patients showed impaired gating of total beta and gamma power. Poor beta gating was associated with negative symptoms. These results demonstrate that schizophrenia patients and α7 heterozygote mice show similar deficits in gating high frequency power. Time-frequency analysis of beta and gamma gating may thus be a translational method of assessing the genetic basis of gating deficits in schizophrenia.
authors: Neuroscience Program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: Jason.Smucny@ucdenver.edu.
authors: Jason
authors: J
authors: Smucny
authors: Korey
authors: K
authors: Wylie
authors: Donald
authors: D
authors: Rojas
authors: Karen
authors: K
authors: Stevens
authors: Ann
authors: A
authors: Olincy
authors: Eugene
authors: E
authors: Kronberg
authors: Lijun
authors: L
authors: Zheng
authors: Jason
authors: J
authors: Tregellas
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D058256:Brain Waves / Q000502:physiology*; D004569:Electroencephalography; D058068:Endophenotypes; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000503:physiopathology*; D055139:Sensory Gating / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000172:deficiency
chemical_list: D064569:alpha7 Nicotinic Acetylcholine Receptor
keywords: Beta; Gamma; Gating; Nicotinic; Schizophrenia
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