University of Hertfordshire

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  • 904854

    Accepted author manuscript, 2 MB, PDF document

  • Saak Ovsepian
  • Volker Steuber
  • Marie Le Berre
  • Liam O'Hara
  • Valerie O'Leary
  • Oliver Dolly
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Original languageEnglish
Pages (from-to)1771-1791
JournalJournal of Physiology
Journal publication dateApr 2013
Volume591
Early online date17 Jan 2013
DOIs
Publication statusPublished - Apr 2013

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

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