QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, November 3, 2004, 24(44):9921-9932; doi:10.1523/JNEUROSCI.2162-04.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (25) Citing Articles via Google Scholar Google Scholar Articles by Chan, C. S. Articles by Surmeier, D. J. Search for Related Content PubMed PubMed Citation Articles by Chan, C. S. Articles by Surmeier, D. J.

 Previous Article  |  Next Article 

Cellular/Molecular
HCN2 and HCN1 Channels Govern the Regularity of Autonomous Pacemaking and Synaptic Resetting in Globus Pallidus Neurons

C. Savio Chan,^1,2 Ryuichi Shigemoto,^2,3 Jeff N. Mercer,¹ and D. James Surmeier¹

¹Department of Physiology and Institute for Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, ²Division of Cerebral Structure, National Institute for Physiological Sciences, Okazaki 444-8787, Japan, and ³Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 332-0012, Japan

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.

Key words: basal ganglia; pacemaking; rhythmicity; cation channel; patch clamp; single-cell RT-PCR; brain slice; ZD7288; cesium; sodium channel; HCN; Ih

---

Received June 3, 2004; revised September 20, 2004; accepted September 22, 2004.

This article has been cited by other articles:

				K. Hashimoto and H. Kita Serotonin Activates Presynaptic and Postsynaptic Receptors in Rat Globus Pallidus J Neurophysiol, April 1, 2008; 99(4): 1723 - 1732. [Abstract] [Full Text] [PDF]

				J. N. Mercer, C. S. Chan, T. Tkatch, J. Held, and D. J. Surmeier Nav1.6 Sodium Channels Are Critical to Pacemaking and Fast Spiking in Globus Pallidus Neurons J. Neurosci., December 5, 2007; 27(49): 13552 - 13566. [Abstract] [Full Text] [PDF]

				C. A. Goddard, E. I. Knudsen, and J. R. Huguenard Intrinsic Excitability of Cholinergic Neurons in the Rat Parabigeminal Nucleus J Neurophysiol, December 1, 2007; 98(6): 3486 - 3493. [Abstract] [Full Text] [PDF]

				M. F. Nolan, J. T. Dudman, P. D. Dodson, and B. Santoro HCN1 Channels Control Resting and Active Integrative Properties of Stellate Cells from Layer II of the Entorhinal Cortex J. Neurosci., November 14, 2007; 27(46): 12440 - 12451. [Abstract] [Full Text] [PDF]

				S. Elias, M. Joshua, J. A. Goldberg, G. Heimer, D. Arkadir, G. Morris, and H. Bergman Statistical Properties of Pauses of the High-Frequency Discharge Neurons in the External Segment of the Globus Pallidus J. Neurosci., March 7, 2007; 27(10): 2525 - 2538. [Abstract] [Full Text] [PDF]

				J. A. Goldberg, C. A. Deister, and C. J. Wilson Response Properties and Synchronization of Rhythmically Firing Dendritic Neurons J Neurophysiol, January 1, 2007; 97(1): 208 - 219. [Abstract] [Full Text] [PDF]

				A. Hernandez, O. Ibanez-Sandoval, A. Sierra, R. Valdiosera, D. Tapia, V. Anaya, E. Galarraga, J. Bargas, and J. Aceves Control of the Subthalamic Innervation of the Rat Globus Pallidus by D2/3 and D4 Dopamine Receptors J Neurophysiol, December 1, 2006; 96(6): 2877 - 2888. [Abstract] [Full Text] [PDF]

				A. Arroyo, B. Kim, R. L. Rasmusson, G. Bett, and J. Yeh Hyperpolarization-Activated Cation Channels Are Expressed in Rat Hypothalamic Gonadotropin-Releasing Hormone (GnRH) Neurons and Immortalized GnRH Neurons Reproductive Sciences, September 1, 2006; 13(6): 442 - 450. [Abstract] [PDF]

				L. Forti, E. Cesana, J. Mapelli, and E. D'Angelo Ionic mechanisms of autorhythmic firing in rat cerebellar Golgi cells J. Physiol., August 1, 2006; 574(3): 711 - 729. [Abstract] [Full Text] [PDF]

				S. Mejia-Gervacio and A. Marty Control of interneurone firing pattern by axonal autoreceptors in the juvenile rat cerebellum J. Physiol., February 15, 2006; 571(1): 43 - 55. [Abstract] [Full Text] [PDF]

				T. Okamoto, M. T. Harnett, and H. Morikawa Hyperpolarization-Activated Cation Current (Ih) Is an Ethanol Target in Midbrain Dopamine Neurons of Mice J Neurophysiol, February 1, 2006; 95(2): 619 - 626. [Abstract] [Full Text] [PDF]

				M. Day, D. B. Carr, S. Ulrich, E. Ilijic, T. Tkatch, and D. J. Surmeier Dendritic Excitability of Mouse Frontal Cortex Pyramidal Neurons Is Shaped by the Interaction among HCN, Kir2, and Kleak Channels J. Neurosci., September 21, 2005; 25(38): 8776 - 8787. [Abstract] [Full Text] [PDF]

				J. Baufreton, J. F. Atherton, D. J. Surmeier, and M. D. Bevan Enhancement of Excitatory Synaptic Integration by GABAergic Inhibition in the Subthalamic Nucleus J. Neurosci., September 14, 2005; 25(37): 8505 - 8517. [Abstract] [Full Text] [PDF]

				J. F. Atherton and M. D. Bevan Ionic Mechanisms Underlying Autonomous Action Potential Generation in the Somata and Dendrites of GABAergic Substantia Nigra Pars Reticulata Neurons In Vitro J. Neurosci., September 7, 2005; 25(36): 8272 - 8281. [Abstract] [Full Text] [PDF]

				N. E. Hallworth and M. D. Bevan Globus Pallidus Neurons Dynamically Regulate the Activity Pattern of Subthalamic Nucleus Neurons through the Frequency-Dependent Activation of Postsynaptic GABAA and GABAB Receptors J. Neurosci., July 6, 2005; 25(27): 6304 - 6315. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help