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Nicotinic Receptor Subtype-Selective Circuit Patterns in the Subthalamic Nucleus

Xiao, Cheng and Miwa, Julie M. and Henderson, Brandon J. and Wang, Ying and Deshpande, Purnima and McKinney, Sheri L. and Lester, Henry A. (2015) Nicotinic Receptor Subtype-Selective Circuit Patterns in the Subthalamic Nucleus. Journal of Neuroscience, 35 (9). pp. 3734-3746. ISSN 0270-6474. PMCID PMC4348180. doi:10.1523/JNEUROSCI.3528-14.2015. https://resolver.caltech.edu/CaltechAUTHORS:20150309-153924379

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Abstract

The glutamatergic subthalamic nucleus (STN) exerts control over motor output through nuclei of the basal ganglia. High-frequency electrical stimuli in the STN effectively alleviate motor symptoms in movement disorders, and cholinergic stimulation boosts this effect. To gain knowledge about the mechanisms of cholinergic modulation in the STN, we studied cellular and circuit aspects of nicotinic acetylcholine receptors (nAChRs) in mouse STN. We discovered two largely divergent microcircuits in the STN; these are regulated in part by either α4β2 or α7 nAChRs. STN neurons containing α4β2 nAChRs (α4β2 neurons) received more glutamatergic inputs, and preferentially innervated GABAergic neurons in the substantia nigra pars reticulata. In contrast, STN neurons containing α7 nAChRs (α7 neurons) received more GABAergic inputs, and preferentially innervated dopaminergic neurons in the substantia nigra pars compacta. Interestingly, local electrical stimuli excited a majority (79%) of α4β2 neurons but exerted strong inhibition in 58% of α7 neurons, indicating an additional diversity of STN neurons: responses to electrical stimulation. Chronic exposure to nicotine selectively affects α4β2 nAChRs in STN: this treatment increased the number of α4β2 neurons, upregulated α4-containing nAChR number and sensitivity, and enhanced the basal firing rate of α4β2 neurons both ex vivo and in vivo. Thus, chronic nicotine enhances the function of the microcircuit involving α4β2 nAChRs. This indicates chronic exposure to nicotinic agonist as a potential pharmacological intervention to alter selectively the balance between these two microcircuits, and may provide a means to inhibit substantia nigra dopaminergic neurons.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1523/JNEUROSCI.3528-14.2015DOIArticle
http://www.jneurosci.org/content/35/9/3734.abstractPublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4348180/PubMed CentralArticle
ORCID:
AuthorORCID
Xiao, Cheng0000-0001-9649-7450
Henderson, Brandon J.0000-0003-0381-028X
Lester, Henry A.0000-0002-5470-5255
Additional Information:© 2015 the authors. After 6 months the work becomes available to the public to copy, distribute, or display under a Creative Commons Attribution 4.0 International (CC BY 4.0) license. Received Aug. 17, 2014; revised Jan. 5, 2015; accepted Jan. 14, 2015. This work was supported by National Institutes of Health Grants DA17279, AG033954, and R21DA033831, and the California Tobacco-Related Disease Research Program Grants 16FT-0066, 17RT-0127, and 19KT-0032.We thank Raad Nashmi and Haijiang Cai for comments and discussion.
Funders:
Funding AgencyGrant Number
NIHDA17279
NIHAG033954
NIHR21DA033831
California Tobacco-Related Disease Research Program16FT-0066
California Tobacco-Related Disease Research Program17RT-0127
California Tobacco-Related Disease Research Program19KT-0032
Subject Keywords:alpha4beta2; alpha7; chronic nicotine; Parkinson’s disease; substantia nigra; upregulation
Issue or Number:9
PubMed Central ID:PMC4348180
DOI:10.1523/JNEUROSCI.3528-14.2015
Record Number:CaltechAUTHORS:20150309-153924379
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150309-153924379
Official Citation:Nicotinic Receptor Subtype-Selective Circuit Patterns in the Subthalamic Nucleus Cheng Xiao, Julie M. Miwa, Brandon J. Henderson, Ying Wang, Purnima Deshpande, Sheri L. McKinney, and Henry A. Lester The Journal of Neuroscience, 4 March 2015, 35(9):3734-3746; doi:10.1523/JNEUROSCI.3528-14.2015
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:55653
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:10 Mar 2015 18:52
Last Modified:10 Nov 2021 20:48

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