Specific disruption of thalamic inputs to the auditory cortex in schizophrenia models.
Publication/Presentation Date
6-6-2014
Abstract
Auditory hallucinations in schizophrenia are alleviated by antipsychotic agents that inhibit D2 dopamine receptors (Drd2s). The defective neural circuits and mechanisms of their sensitivity to antipsychotics are unknown. We identified a specific disruption of synaptic transmission at thalamocortical glutamatergic projections in the auditory cortex in murine models of schizophrenia-associated 22q11 deletion syndrome (22q11DS). This deficit is caused by an aberrant elevation of Drd2 in the thalamus, which renders 22q11DS thalamocortical projections sensitive to antipsychotics and causes a deficient acoustic startle response similar to that observed in schizophrenic patients. Haploinsufficiency of the microRNA-processing gene Dgcr8 is responsible for the Drd2 elevation and hypersensitivity of auditory thalamocortical projections to antipsychotics. This suggests that Dgcr8-microRNA-Drd2-dependent thalamocortical disruption is a pathogenic event underlying schizophrenia-associated psychosis.
Volume
344
Issue
6188
First Page
1178
Last Page
1182
ISSN
1095-9203
Published In/Presented At
Chun, S., Westmoreland, J. J., Bayazitov, I. T., Eddins, D., Pani, A. K., Smeyne, R. J., Yu, J., Blundon, J. A., & Zakharenko, S. S. (2014). Specific disruption of thalamic inputs to the auditory cortex in schizophrenia models. Science (New York, N.Y.), 344(6188), 1178–1182. https://doi.org/10.1126/science.1253895
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
24904170
Department(s)
Administration and Leadership
Document Type
Article