Enhanced GABA Transmission Drives Bradykinesia Following Loss of Dopamine D2 Receptor Signaling.

ABSTRACT: Bradykinesia is a prominent phenotype of Parkinson's disease, depression, and other neurological conditions. Disruption of dopamine (DA) transmission plays an important role, but progress in understanding the exact mechanisms driving slowness of movement has been impeded due to the heterogeneity of DA receptor distribution on multiple cell types within the striatum. Here we show that selective deletion of DA D2 receptors (D2Rs) from indirect-pathway medium spiny neurons (iMSNs) is sufficient to impair locomotor activity, phenocopying DA depletion models of Parkinson's disease, despite this mouse model having intact DA transmission. There was a robust enhancement of GABAergic transmission and a reduction of in vivo firing in striatal and pallidal neurons. Mimicking D2R signaling in iMSNs wi

SUBMITTER: Lemos JC 

PROVIDER: S-EPMC4882167 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature