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

doi:10.1016/j.neuron.2014.12.022

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

Neuroscience

Research output: Contribution to journal › Article › peer-review

100 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 GABA_A 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 language	English (US)
Pages (from-to)	364-376
Number of pages	13
Journal	Neuron
Volume	85
Issue number	2
DOIs	https://doi.org/10.1016/j.neuron.2014.12.022
State	Published - Jan 21 2015

Funding

This study was funded by NIH NINDS Grants 2R37 NS041280 (to M.D.B.), 2P50 NS047085 (to D.J.S. and M.D.B), and P30 NS054850 (to D.J.S. and D.W.). We thank J. Baufreton, C.S. Chan, H. Kita, P.J. Magill, and C.J. Wilson for comments on the manuscript and S. Ulrich, D.R. Schowalter, and M. Alicea for management of mouse colonies.

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neuron.2014.12.022

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title = "Heterosynaptic regulation of external globus pallidus inputs to the subthalamic nucleus by the motor cortex",

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.",

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AU - Bevan, Mark D.

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

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