HCN channelopathy in external globus pallidus neurons in models of Parkinson's disease

C. Savio Chan, Kelly E. Glajch, Tracy S. Gertler, Jaime N. Guzman, Jeff N. Mercer, Alan S. Lewis, Alan B. Goldberg, Tatiana Tkatch, Ryuichi Shigemoto, Sheila M. Fleming, Dane M. Chetkovich, Pavel Osten, Hitoshi Kita, D. James Surmeier

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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.

Original languageEnglish (US)
Pages (from-to)85-94
Number of pages10
JournalNature Neuroscience
Volume14
Issue number1
DOIs
StatePublished - Jan 1 2011

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Channelopathies
Globus Pallidus
Cyclic Nucleotides
Parkinson Disease
Dopamine
Cyclic Nucleotide-Gated Cation Channels
Neurons
Ion Channels
Neurodegenerative Diseases
Down-Regulation

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Chan, C. S., Glajch, K. E., Gertler, T. S., Guzman, J. N., Mercer, J. N., Lewis, A. S., ... Surmeier, D. J. (2011). HCN channelopathy in external globus pallidus neurons in models of Parkinson's disease. Nature Neuroscience, 14(1), 85-94. https://doi.org/10.1038/nn.2692

HCN channelopathy in external globus pallidus neurons in models of Parkinson's disease. / Chan, C. Savio; Glajch, Kelly E.; Gertler, Tracy S.; Guzman, Jaime N.; Mercer, Jeff N.; Lewis, Alan S.; Goldberg, Alan B.; Tkatch, Tatiana; Shigemoto, Ryuichi; Fleming, Sheila M.; Chetkovich, Dane M.; Osten, Pavel; Kita, Hitoshi; Surmeier, D. James.

In: Nature Neuroscience, Vol. 14, No. 1, 01.01.2011, p. 85-94.

Research output: Contribution to journalArticle

Chan, CS, Glajch, KE, Gertler, TS, Guzman, JN, Mercer, JN, Lewis, AS, Goldberg, AB, Tkatch, T, Shigemoto, R, Fleming, SM, Chetkovich, DM, Osten, P, Kita, H & Surmeier, DJ 2011, 'HCN channelopathy in external globus pallidus neurons in models of Parkinson's disease', Nature Neuroscience, vol. 14, no. 1, pp. 85-94. https://doi.org/10.1038/nn.2692
Chan CS, Glajch KE, Gertler TS, Guzman JN, Mercer JN, Lewis AS et al. HCN channelopathy in external globus pallidus neurons in models of Parkinson's disease. Nature Neuroscience. 2011 Jan 1;14(1):85-94. https://doi.org/10.1038/nn.2692
Chan, C. Savio ; Glajch, Kelly E. ; Gertler, Tracy S. ; Guzman, Jaime N. ; Mercer, Jeff N. ; Lewis, Alan S. ; Goldberg, Alan B. ; Tkatch, Tatiana ; Shigemoto, Ryuichi ; Fleming, Sheila M. ; Chetkovich, Dane M. ; Osten, Pavel ; Kita, Hitoshi ; Surmeier, D. James. / HCN channelopathy in external globus pallidus neurons in models of Parkinson's disease. In: Nature Neuroscience. 2011 ; Vol. 14, No. 1. pp. 85-94.
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