Autonomous initiation and propagation of action potentials in neurons of the subthalamic nucleus

Jeremy F. Atherton, David L. Wokosin, Sankari Ramanathan, Mark D. Bevan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

The activity of the subthalamic nucleus (STN) is intimately related to movement and is generated, in part, by voltage-dependent Na+ (Nav) channels that drive autonomous firing. In order to determine the principles underlying the initiation and propagation of action potentials in STN neurons, 2-photon laser scanning microscopy was used to guide tight-seal whole-cell somatic and loose-seal cell-attached axonal/dendritic patch-clamp recordings and compartment-selective ion channel manipulation in rat brain slices. Action potentials were first detected in a region that corresponded most closely to the unmyelinated axon initial segment, as defined by Golgi and ankyrinG labelling. Following initiation, action potentials propagated reliably into axonal and somatodendritic compartments with conduction velocities of ∼5 m s-1 and ∼0.7 m s-1, respectively. Action potentials generated by neurons with axons truncated within or beyond the axon initial segment were not significantly different. However, axon initial segment and somatic but not dendritic or more distal axonal application of low [Na+]ACSF or the selective Nav channel blocker tetrodotoxin consistently depolarized action potential threshold. Finally, somatodendritic but not axonal application of GABA evoked large, rapid inhibitory currents in concordance with electron microscopic analyses, which revealed that the somatodendritic compartment was the principal target of putative inhibitory inputs. Together the data are consistent with the conclusions that in STN neurons the axon initial segment and soma express an excess of Nav channels for the generation of autonomous activity, while synaptic activation of somatodendritic GABAA receptors regulates the axonal initiation of action potentials.

Original languageEnglish (US)
Pages (from-to)5679-5700
Number of pages22
JournalJournal of physiology
Volume586
Issue number23
DOIs
StatePublished - Dec 2008

ASJC Scopus subject areas

  • Physiology

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