HCN2 and HCN1 channels govern the regularity of autonomous pacemaking and synaptic resetting in globus pallidus neurons

S. Chan, R. Shigemoto, J. Mercer, J. Surmeier, Journal of Neuroscience 24 (2004) 9921–9932.

Download
No fulltext has been uploaded. References only!

Journal Article | Published
Author
Chan, Savio; Shigemoto, RyuichiIST Austria ; Mercer, Jeff N; Surmeier, James D
Abstract
The globus pallidus (GP) is a critical component of the basal ganglia circuitry controlling motor behavior. Dysregulation of GP activity has been implicated in a number of psychomotor disorders, including Parkinson's disease (PD), in which a cardinal feature of the pathophysiology is an alteration in the pattern and synchrony of discharge in GP neurons. Yet the determinants of this activity in GP neurons are poorly understood. To help fill this gap, electrophysiological, molecular, and computational approaches were used to identify and characterize GABAergic GP neurons in tissue slices from rodents. In vitro, GABAergic GP neurons generate a regular, autonomous, single-spike pacemaker activity. Hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels make an important contribution to this process: their blockade with ZD7288 significantly slowed discharge rate and decreased its regularity. HCN currents evoked by somatic voltage clamp had fast and slow components. Single-cell RT-PCR and immunohistochemical approaches revealed robust expression of HCN2 subunits as well as significant levels of HCN1 subunits in GABAergic GP neurons. Transient activation of striatal GABAergic input to GP neurons led to a resetting of rhythmic discharge that was dependent on HCN currents. Simulations suggested that the ability of transient striatal GABAergic input to reset pacemaking was dependent on dendritic HCN2/HCN1 channels. Together, these studies show that HCN channels in GABAergic GP neurons are key determinants of the regularity and rate of pacemaking as well as striatal resetting of this activity, implicating HCN channels in the emergence of synchrony in PD.
Publishing Year
Date Published
2004-11-03
Journal Title
Journal of Neuroscience
Volume
24
Issue
44
Page
9921 - 9932
IST-REx-ID

Cite this

Chan S, Shigemoto R, Mercer J, Surmeier J. HCN2 and HCN1 channels govern the regularity of autonomous pacemaking and synaptic resetting in globus pallidus neurons. Journal of Neuroscience. 2004;24(44):9921-9932. doi:10.1523/JNEUROSCI.2162-04.2004
Chan, S., Shigemoto, R., Mercer, J., & Surmeier, J. (2004). HCN2 and HCN1 channels govern the regularity of autonomous pacemaking and synaptic resetting in globus pallidus neurons. Journal of Neuroscience, 24(44), 9921–9932. https://doi.org/10.1523/JNEUROSCI.2162-04.2004
Chan, Savio, Ryuichi Shigemoto, Jeff Mercer, and James Surmeier. “HCN2 and HCN1 Channels Govern the Regularity of Autonomous Pacemaking and Synaptic Resetting in Globus Pallidus Neurons.” Journal of Neuroscience 24, no. 44 (2004): 9921–32. https://doi.org/10.1523/JNEUROSCI.2162-04.2004.
S. Chan, R. Shigemoto, J. Mercer, and J. Surmeier, “HCN2 and HCN1 channels govern the regularity of autonomous pacemaking and synaptic resetting in globus pallidus neurons,” Journal of Neuroscience, vol. 24, no. 44, pp. 9921–9932, 2004.
Chan S, Shigemoto R, Mercer J, Surmeier J. 2004. HCN2 and HCN1 channels govern the regularity of autonomous pacemaking and synaptic resetting in globus pallidus neurons. Journal of Neuroscience. 24(44), 9921–9932.
Chan, Savio, et al. “HCN2 and HCN1 Channels Govern the Regularity of Autonomous Pacemaking and Synaptic Resetting in Globus Pallidus Neurons.” Journal of Neuroscience, vol. 24, no. 44, Society for Neuroscience, 2004, pp. 9921–32, doi:10.1523/JNEUROSCI.2162-04.2004.

Export

Marked Publications

Open Data IST Research Explorer

Search this title in

Google Scholar