Selective participation of somatodendritic HCN channels in inhibitory but not excitatory synaptic integration in neurons of the subthalamic nucleus
Journal of Neuroscience. 2010-11-24; 30(47): 16025-16040
DOI: 10.1523/JNEUROSCI.3898-10.2010
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1. J Neurosci. 2010 Nov 24;30(47):16025-40. doi: 10.1523/JNEUROSCI.3898-10.2010.
Selective participation of somatodendritic HCN channels in inhibitory but not
excitatory synaptic integration in neurons of the subthalamic nucleus.
Atherton JF(1), Kitano K, Baufreton J, Fan K, Wokosin D, Tkatch T, Shigemoto R,
Surmeier DJ, Bevan MD.
Author information:
(1)Department of Physiology, Northwestern University, Chicago, IL, USA.
The activity patterns of subthalamic nucleus (STN) neurons are intimately linked
to motor function and dysfunction and arise through the complex interaction of
intrinsic properties and inhibitory and excitatory synaptic inputs. In many
neurons, hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play
key roles in intrinsic excitability and synaptic integration both under normal
conditions and in disease states. However, in STN neurons, which strongly express
HCN channels, their roles remain relatively obscure. To address this deficit,
complementary molecular and cellular electrophysiological, imaging, and
computational approaches were applied to the rat STN. Molecular profiling
demonstrated that individual STN neurons express mRNA encoding several HCN
subunits, with HCN2 and 3 being the most abundant. Light and electron microscopic
analysis showed that HCN2 subunits are strongly expressed and distributed
throughout the somatodendritic plasma membrane. Voltage-, current-, and
dynamic-clamp analysis, two-photon Ca(2+) imaging, and computational modeling
revealed that HCN channels are activated by GABA(A) receptor-mediated inputs and
thus limit synaptic hyperpolarization and deinactivation of low-voltage-activated
Ca(2+) channels. Although HCN channels also limited the temporal summation of
EPSPs, generated through two-photon uncaging of glutamate, this action was
largely shunted by GABAergic inhibition that was necessary for HCN channel
activation. Together the data demonstrate that HCN channels in STN neurons
selectively counteract GABA(A) receptor-mediated inhibition arising from the
globus pallidus and thus promote single-spike activity rather than rebound burst
firing.
DOI: 10.1523/JNEUROSCI.3898-10.2010
PMCID: PMC3073577
PMID: 21106841 [Indexed for MEDLINE]