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Bidirectional dopamine modulation of excitatory and inhibitory synaptic inputs to subthalamic neuron subsets containing α4β2 or α7 nAChRs

Zhou, Chunyi and Gu, Weixin and Wu, Haichuan and Yan, Xiang and Deshpande, Purnima and Xiao, Cheng and Lester, Henry A. (2019) Bidirectional dopamine modulation of excitatory and inhibitory synaptic inputs to subthalamic neuron subsets containing α4β2 or α7 nAChRs. Neuropharmacology, 148 . pp. 220-228. ISSN 0028-3908. https://resolver.caltech.edu/CaltechAUTHORS:20190123-075807331

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Abstract

The subthalamic nucleus (STN) possesses microcircuits distinguished by subtypes of nicotinic acetylcholine receptors (nAChRs). Although dysfunction of the STN is well-known in Parkinson's disease, there is still little information about whether dopamine differentially modulates excitatory and inhibitory synaptic inputs to STN neurons expressing different nAChR subtypes. To address this issue, we performed brain slice patch-clamp recordings on STN neurons, while we pharmacologically manipulated dopaminergic inputs. In STN neuron subsets containing either α4β2 or α7 nAChRs, D_1 and D_2 receptors respectively enhanced and inhibited spontaneous inhibitory and excitatory postsynaptic currents (sIPSCs and sEPSCs) and firing rates. The elevation of dopamine levels resulted in diverse regulations of synaptic transmission in these two neuron subsets, and interestingly, the dopamine regulation of sIPSCs significantly correlated with that of sEPSCs. Surprisingly, depletion of dopamine either by reserpine treatment or by unilateral 6-OHDA lesion of nigrostriatal dopaminergic neurons did not alter synaptic inputs to STN neurons, but STN neurons in the 6-OHDA-lesioned side exhibited hyperactivity. In summary, dopamine regulated both GABAergic and glutamatergic synaptic inputs to STN neuron subsets containing either α4β2 or α7 nAChRs, forming a balancing machinery to control neuronal activity. In parkinsonian mice, postsynaptic mechanisms may exist and contribute to the hyperactivity of STN neurons.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.neuropharm.2019.01.015DOIArticle
ORCID:
AuthorORCID
Xiao, Cheng0000-0001-9649-7450
Lester, Henry A.0000-0002-5470-5255
Additional Information:© 2019 Elsevier Ltd. Received 10 August 2018, Revised 10 January 2019, Accepted 14 January 2019, Available online 17 January 2019. This work was supported by Michael J. Fox Foundation (11345), National Institutes of Health (AG033954), the California Tobacco-Related Disease Research Program Grants, National Natural Science Foundation of China (81701100, 81870891), Fund for Jiangsu Province Specially-Appointed Professor (C.X., C.Z.), Natural Science Foundation of Jiangsu Province (BK20171160), The Natural Science Foundation of the Jiangsu Higher Education Institutions of China (17KJA320007, 18KJA320009), Jiangsu Province Fund for Dominant Discipline (Anesthesiology).
Funders:
Funding AgencyGrant Number
Michael J. Fox Foundation11345
NIHAG033954
California Tobacco-Related Disease Research ProgramUNSPECIFIED
National Natural Science Foundation of China81701100
National Natural Science Foundation of China81870891
Fund for Jiangsu ProvinceUNSPECIFIED
Natural Science Foundation of Jiangsu ProvinceBK20171160
Jiangsu Higher Education Institutions of China17KJA320007
Jiangsu Higher Education Institutions of China18KJA320009
Jiangsu Province Fund for Dominant DisciplineUNSPECIFIED
Subject Keywords:Nicotinic acetylcholine receptor; α4β2; α7; Subthalamic nucleus; Dopamine receptors
Record Number:CaltechAUTHORS:20190123-075807331
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190123-075807331
Official Citation:Chunyi Zhou, Weixin Gu, Haichuan Wu, Xiang Yan, Purnima Deshpande, Cheng Xiao, Henry A. Lester, Bidirectional dopamine modulation of excitatory and inhibitory synaptic inputs to subthalamic neuron subsets containing α4β2 or α7 nAChRs, Neuropharmacology, Volume 148, 2019, Pages 220-228, ISSN 0028-3908, https://doi.org/10.1016/j.neuropharm.2019.01.015. (http://www.sciencedirect.com/science/article/pii/S0028390818304969)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:92410
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:23 Jan 2019 17:27
Last Modified:08 Oct 2019 21:05

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