Rapid alterations in corticostriatal ensemble coordination during acute dopamine-dependent motor dysfunction.

Published

Journal Article

Dopaminergic dysregulation can cause motor dysfunction, but the mechanisms underlying dopamine-related motor disorders remain under debate. We used an inducible and reversible pharmacogenetic approach in dopamine transporter knockout mice to investigate the simultaneous activity of neuronal ensembles in the dorsolateral striatum and primary motor cortex during hyperdopaminergia ( approximately 500% of controls) with hyperkinesia, and after rapid and profound dopamine depletion (<0.2%) with akinesia in the same animal. Surprisingly, although most cortical and striatal neurons ( approximately 70%) changed firing rate during the transition between dopamine-related hyperkinesia and akinesia, the overall cortical firing rate remained unchanged. Conversely, neuronal oscillations and ensemble activity coordination within and between cortex and striatum did change rapidly between these periods. During hyperkinesia, corticostriatal activity became largely asynchronous, while during dopamine-depletion the synchronicity increased. Thus, dopamine-related disorders like Parkinson's disease may not stem from changes in the overall levels of cortical activity, but from dysfunctional activity coordination in corticostriatal circuits.

Full Text

Duke Authors

Cited Authors

  • Costa, RM; Lin, S-C; Sotnikova, TD; Cyr, M; Gainetdinov, RR; Caron, MG; Nicolelis, MAL

Published Date

  • October 2006

Published In

Volume / Issue

  • 52 / 2

Start / End Page

  • 359 - 369

PubMed ID

  • 17046697

Pubmed Central ID

  • 17046697

Electronic International Standard Serial Number (EISSN)

  • 1097-4199

International Standard Serial Number (ISSN)

  • 0896-6273

Digital Object Identifier (DOI)

  • 10.1016/j.neuron.2006.07.030

Language

  • eng