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Dendritic HCN2 channels constrain glutamate-driven excitability in reticular thalamic neurons.
J Neurosci. 2007 Aug 08; 27(32):8719-32.JN

Abstract

Hyperpolarization activated cyclic nucleotide (HCN) gated channels conduct a current, I(h); how I(h) influences excitability and spike firing depends primarily on channel distribution in subcellular compartments. For example, dendritic expression of HCN1 normalizes somatic voltage responses and spike output in hippocampal and cortical neurons. We reported previously that HCN2 is predominantly expressed in dendritic spines in reticular thalamic nucleus (RTN) neurons, but the functional impact of such nonsomatic HCN2 expression remains unknown. We examined the role of HCN2 expression in regulating RTN excitability and GABAergic output from RTN to thalamocortical relay neurons using wild-type and HCN2 knock-out mice. Pharmacological blockade of I(h) significantly increased spike firing in RTN neurons and large spontaneous IPSC frequency in relay neurons; conversely, pharmacological enhancement of HCN channel function decreased spontaneous IPSC frequency. HCN2 deletion abolished I(h) in RTN neurons and significantly decreased sensitivity to 8-bromo-cAMP and lamotrigine. Recapitulating the effects of I(h) block, HCN2 deletion increased both temporal summation of EPSPs in RTN neurons as well as GABAergic output to postsynaptic relay neurons. The enhanced excitability of RTN neurons after I(h) block required activation of ionotropic glutamate receptors; consistent with this was the colocalization of HCN2 and glutamate receptor 4 subunit immunoreactivities in dendritic spines of RTN neurons. The results indicate that, in mouse RTN neurons, HCN2 is the primary functional isoform underlying I(h) and expression of HCN2 constrains excitatory synaptic integration.

Authors+Show Affiliations

C. V. Starr Laboratory for Molecular Neuropharmacology, Department of Anesthesiology, Weill Medical College, Cornell University, New York, New York 10021, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17687049

Citation

Ying, Shui-Wang, et al. "Dendritic HCN2 Channels Constrain Glutamate-driven Excitability in Reticular Thalamic Neurons." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 27, no. 32, 2007, pp. 8719-32.
Ying SW, Jia F, Abbas SY, et al. Dendritic HCN2 channels constrain glutamate-driven excitability in reticular thalamic neurons. J Neurosci. 2007;27(32):8719-32.
Ying, S. W., Jia, F., Abbas, S. Y., Hofmann, F., Ludwig, A., & Goldstein, P. A. (2007). Dendritic HCN2 channels constrain glutamate-driven excitability in reticular thalamic neurons. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 27(32), 8719-32.
Ying SW, et al. Dendritic HCN2 Channels Constrain Glutamate-driven Excitability in Reticular Thalamic Neurons. J Neurosci. 2007 Aug 8;27(32):8719-32. PubMed PMID: 17687049.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dendritic HCN2 channels constrain glutamate-driven excitability in reticular thalamic neurons. AU - Ying,Shui-Wang, AU - Jia,Fan, AU - Abbas,Syed Y, AU - Hofmann,Franz, AU - Ludwig,Andreas, AU - Goldstein,Peter A, PY - 2007/8/10/pubmed PY - 2007/8/30/medline PY - 2007/8/10/entrez SP - 8719 EP - 32 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J Neurosci VL - 27 IS - 32 N2 - Hyperpolarization activated cyclic nucleotide (HCN) gated channels conduct a current, I(h); how I(h) influences excitability and spike firing depends primarily on channel distribution in subcellular compartments. For example, dendritic expression of HCN1 normalizes somatic voltage responses and spike output in hippocampal and cortical neurons. We reported previously that HCN2 is predominantly expressed in dendritic spines in reticular thalamic nucleus (RTN) neurons, but the functional impact of such nonsomatic HCN2 expression remains unknown. We examined the role of HCN2 expression in regulating RTN excitability and GABAergic output from RTN to thalamocortical relay neurons using wild-type and HCN2 knock-out mice. Pharmacological blockade of I(h) significantly increased spike firing in RTN neurons and large spontaneous IPSC frequency in relay neurons; conversely, pharmacological enhancement of HCN channel function decreased spontaneous IPSC frequency. HCN2 deletion abolished I(h) in RTN neurons and significantly decreased sensitivity to 8-bromo-cAMP and lamotrigine. Recapitulating the effects of I(h) block, HCN2 deletion increased both temporal summation of EPSPs in RTN neurons as well as GABAergic output to postsynaptic relay neurons. The enhanced excitability of RTN neurons after I(h) block required activation of ionotropic glutamate receptors; consistent with this was the colocalization of HCN2 and glutamate receptor 4 subunit immunoreactivities in dendritic spines of RTN neurons. The results indicate that, in mouse RTN neurons, HCN2 is the primary functional isoform underlying I(h) and expression of HCN2 constrains excitatory synaptic integration. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/17687049/Dendritic_HCN2_channels_constrain_glutamate_driven_excitability_in_reticular_thalamic_neurons_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=17687049 DB - PRIME DP - Unbound Medicine ER -