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A Defined Heteromeric KV1 Channel Stabilizes the Intrinsic Pacemaking and Regulates the Efferent Code of Deep Cerebellar Nuclear Neurons to Thalamic Targets. / Ovsepian, Saak ; Steuber, Volker; Le Berre, Marie; O'Hara, Liam; O'Leary, Valerie; Dolly, Oliver.

In: Journal of Physiology, Vol. 591, 04.2013, p. 1771-1791.

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@article{e6779b1bff6043c3b038988e236a5e4e,
title = "A Defined Heteromeric KV1 Channel Stabilizes the Intrinsic Pacemaking and Regulates the Efferent Code of Deep Cerebellar Nuclear Neurons to Thalamic Targets",
abstract = "The output of the cerebellum to the motor axis of the central nervous system is orchestrated mainly by synaptic inputs and intrinsic pacemaker activity of deep cerebellar nuclear (DCN) projection neurons. Herein, we demonstrate that the soma of these cells is enriched with KV1 channels produced by mandatory multi-merization of KV1.1, 1.2 α and KV β2 subunits. Being constitutively active, the K+ current (IKV1) mediated by these channels stabilizes the rate and regulates the temporal precision of self-sustained firing of these neurons. Placed strategically, IKV1 provides a powerful counter-balance to prolonged depolarizing inputs, attenuates the rebound excitation, and dampens the membrane potential bi-stability. Somatic location with low activation threshold render IKV1 instrumental in voltage-dependent de-coupling of the axon initial segment from the cell body of projection neurons, impeding invasion of backpropagating initial segment action potentials into the somato-dendr itic compartment. The latter also promotes the dominance of clock like somatic pace-making in driving the regenerative firing activity of these neurons, to encode time variant inputs with high fidelity. Through the use of multi-compartmental modeling and retro-axonal labeling, the physiological significance of the described functions for processing and communication of information from the lateral DCN to thalamic relay nuclei is established",
author = "Saak Ovsepian and Volker Steuber and {Le Berre}, Marie and Liam O'Hara and Valerie O'Leary and Oliver Dolly",
year = "2013",
month = "4",
doi = "10.1113/jphysiol.2012.249706",
language = "English",
volume = "591",
pages = "1771--1791",
journal = "Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell",

}

RIS

TY - JOUR

T1 - A Defined Heteromeric KV1 Channel Stabilizes the Intrinsic Pacemaking and Regulates the Efferent Code of Deep Cerebellar Nuclear Neurons to Thalamic Targets

AU - Ovsepian, Saak

AU - Steuber, Volker

AU - Le Berre, Marie

AU - O'Hara, Liam

AU - O'Leary, Valerie

AU - Dolly, Oliver

PY - 2013/4

Y1 - 2013/4

N2 - The output of the cerebellum to the motor axis of the central nervous system is orchestrated mainly by synaptic inputs and intrinsic pacemaker activity of deep cerebellar nuclear (DCN) projection neurons. Herein, we demonstrate that the soma of these cells is enriched with KV1 channels produced by mandatory multi-merization of KV1.1, 1.2 α and KV β2 subunits. Being constitutively active, the K+ current (IKV1) mediated by these channels stabilizes the rate and regulates the temporal precision of self-sustained firing of these neurons. Placed strategically, IKV1 provides a powerful counter-balance to prolonged depolarizing inputs, attenuates the rebound excitation, and dampens the membrane potential bi-stability. Somatic location with low activation threshold render IKV1 instrumental in voltage-dependent de-coupling of the axon initial segment from the cell body of projection neurons, impeding invasion of backpropagating initial segment action potentials into the somato-dendr itic compartment. The latter also promotes the dominance of clock like somatic pace-making in driving the regenerative firing activity of these neurons, to encode time variant inputs with high fidelity. Through the use of multi-compartmental modeling and retro-axonal labeling, the physiological significance of the described functions for processing and communication of information from the lateral DCN to thalamic relay nuclei is established

AB - The output of the cerebellum to the motor axis of the central nervous system is orchestrated mainly by synaptic inputs and intrinsic pacemaker activity of deep cerebellar nuclear (DCN) projection neurons. Herein, we demonstrate that the soma of these cells is enriched with KV1 channels produced by mandatory multi-merization of KV1.1, 1.2 α and KV β2 subunits. Being constitutively active, the K+ current (IKV1) mediated by these channels stabilizes the rate and regulates the temporal precision of self-sustained firing of these neurons. Placed strategically, IKV1 provides a powerful counter-balance to prolonged depolarizing inputs, attenuates the rebound excitation, and dampens the membrane potential bi-stability. Somatic location with low activation threshold render IKV1 instrumental in voltage-dependent de-coupling of the axon initial segment from the cell body of projection neurons, impeding invasion of backpropagating initial segment action potentials into the somato-dendr itic compartment. The latter also promotes the dominance of clock like somatic pace-making in driving the regenerative firing activity of these neurons, to encode time variant inputs with high fidelity. Through the use of multi-compartmental modeling and retro-axonal labeling, the physiological significance of the described functions for processing and communication of information from the lateral DCN to thalamic relay nuclei is established

UR - http://www.scopus.com/inward/record.url?scp=84875658567&partnerID=8YFLogxK

U2 - 10.1113/jphysiol.2012.249706

DO - 10.1113/jphysiol.2012.249706

M3 - Article

VL - 591

SP - 1771

EP - 1791

JO - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

ER -