| First Author | Chun S | Year | 2014 |
| Journal | Science | Volume | 344 |
| Issue | 6188 | Pages | 1178-82 |
| PubMed ID | 24904170 | Mgi Jnum | J:211625 |
| Mgi Id | MGI:5575787 | Doi | 10.1126/science.1253895 |
| Citation | Chun S, et al. (2014) Specific disruption of thalamic inputs to the auditory cortex in schizophrenia models. Science 344(6188):1178-82 |
| abstractText | 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. |
