Heterosynaptic regulation of external globus pallidus inputs to the subthalamic nucleus by the motor cortex

Hong Yuan Chu, Jeremy F. Atherton, David Wokosin, D. James Surmeier, Mark D. Bevan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

The two principal movement-suppressing pathways of the basal ganglia, the so-called hyperdirect and indirect pathways, interact within the subthalamic nucleus (STN). An appropriate level and pattern of hyperdirect pathway cortical excitation and indirect pathway external globus pallidus (GPe) inhibition ofthe STN are critical for normal movement and aregreatly perturbed in Parkinson's disease. Here we demonstrate that motor cortical inputs to the STN heterosynaptically regulate, through activation of postsynaptic NMDA receptors, the number of functional GABAA receptor-mediated GPe-STN inputs. Therefore, a homeostatic mechanism, intrinsic tothe STN, balances cortical excitation by adjusting the strength of GPe inhibition. However, following the loss of dopamine, excessive cortical activation of STN NMDA receptors triggers GPe-STN inputs tostrengthen abnormally, contributing to the emergence of pathological, correlated activity.

Original languageEnglish (US)
Pages (from-to)364-376
Number of pages13
JournalNeuron
Volume85
Issue number2
DOIs
StatePublished - Jan 21 2015

ASJC Scopus subject areas

  • Neuroscience(all)

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