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. doi:10.1016/j.neuropharm.2019.01.015. 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.
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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). | ||||||||||||||||||||||
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Subject Keywords: | Nicotinic acetylcholine receptor; α4β2; α7; Subthalamic nucleus; Dopamine receptors | ||||||||||||||||||||||
DOI: | 10.1016/j.neuropharm.2019.01.015 | ||||||||||||||||||||||
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: | 16 Nov 2021 03:50 |
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