Chan, C. S., Glajch, K. E., Gertler, T. S., Guzman, J. N., Mercer, J. N., Lewis, A. S., Goldberg, A. B., Tkatch, T., Shigemoto, R., Fleming, S. M., Chetkovich, D. M., Osten, P., Kita, H., Surmeier, D. J. (January 2011) HCN channelopathy in external globus pallidus neurons in models of Parkinson's disease. Nature Neuroscience, 14 (1). 85-U117. ISSN 1097-6256
Abstract
Parkinson's disease is a common neurodegenerative disorder characterized by a profound motor disability that is traceable to the emergence of synchronous, rhythmic spiking in neurons of the external segment of the globus pallidus (GPe). The origins of this pathophysiology are poorly defined for the generation of pacemaking. After the induction of a parkinsonian state in mice, there was a progressive decline in autonomous GPe pacemaking, which normally serves to desynchronize activity. The loss was attributable to the downregulation of an ion channel that is essential in pacemaking, the hyperpolarization and cyclic nucleotide-gated (HCN) channel. Viral delivery of HCN2 subunits restored pacemaking and reduced burst spiking in GPe neurons. However, the motor disability induced by dopamine (DA) depletion was not reversed, suggesting that the loss of pacemaking was a consequence, rather than a cause, of key network pathophysiology, a conclusion that is consistent with the ability of L-type channel antagonists to attenuate silencing after DA depletion.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | BASAL GANGLIA IN-VITRO ABSENCE EPILEPSY DOPAMINE PLASTICITY OSCILLATIONS DISORDERS RECEPTORS MICE PATHOPHYSIOLOGY |
| Subjects: | diseases & disorders > nervous system diseases and disorders > Parkinson's disease organism description > animal > mammal > rodent > mouse |
| CSHL Authors: | |
| Communities: | CSHL labs > Osten lab |
| Highlight: | Osten, Pavel |
| Depositing User: | CSHL Librarian |
| Date: | January 2011 |
| Date Deposited: | 07 Nov 2011 20:30 |
| Last Modified: | 18 Nov 2014 16:30 |
| PMCID: | PMC3058391 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/15614 |
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