GABAergic control of the subthalamic nucleus

Mark D. Bevan*, Nicholas E. Hallworth, Jérôme Baufreton

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

39 Scopus citations

Abstract

The glutamatergic subthalamic nucleus (STN) is a key component of the basal ganglia, a group of subcortical brain nuclei important for voluntary movement and the site of dysfunction in Parkinson's disease. The rate and pattern of STN activity is precisely regulated by the reciprocally connected GABAergic external globus pallidus (GPe) and glutamatergic afferents from the cortex. Subthalamic neurons possess intrinsic membrane properties that underlie the autonomous generation of action potentials and complex forms of synaptic integration. Thus, GABA acting at GABAA and/or GABAB receptors can inhibit/reset autonomous activity by deactivating postsynaptic voltage-dependent Na+ (Nav) channels and generate sufficient hyperpolarization for rebound burst firing, through the de-inactivation of postsynaptic voltage-dependent Ca2+ (Cav) and Nav channels. Feedback inhibition from the GPe can therefore paradoxically and transiently increase the efficacy of subsequent excitatory synaptic inputs, and thus enhance the response of the STN to rhythmic input from the cortex. Evidence is also provided that dopamine acting at post- and presynaptic receptors in the STN may, through actions on the integrative properties of STN neurons and activity-dependent synaptic plasticity, be critical for the patterning of STN neuronal activity in vivo. Taken together, these discoveries may be relevant for the emergence of correlated, rhythmic, burst firing in the dopamine-depleted STN of patients with PD.

Original languageEnglish (US)
Title of host publicationGaba and the Basal Ganglia From Molecules to Systems
EditorsJames Tepper, Elizabeth Abercrombie, Paul Bolam
Pages173-188
Number of pages16
DOIs
StatePublished - 2007

Publication series

NameProgress in Brain Research
Volume160
ISSN (Print)0079-6123

Keywords

  • Parkinson's disease
  • cortex
  • dopamine
  • excitation
  • inhibition
  • oscillation
  • synaptic integration

ASJC Scopus subject areas

  • Neuroscience(all)

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