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- Title
Medial Habenula Output Circuit Mediated by α5 Nicotinic Receptor-Expressing GABAergic Neurons in the Interpeduncular Nucleus.
- Authors
Yun-Wei A. Hsu; Tempest, Lynne; Quina, Lely A.; Wei, Aguan D.; Hongkui Zeng; Turner, Eric E.
- Abstract
The Chrna5 gene encodes theα5 nicotinic acetylcholine receptor subunit, an "accessory" subunit of pentameric nicotinic receptors, that has been shown to play a role in nicotine-related behaviors in rodents and is genetically linked to smoking behavior in humans. Here we have used a BAC transgenic mouse line,α5GFP, to examine the cellular phenotype, connectivity, and function ofα5-expressing neurons. Although the medial habenula (MHb) has been proposed as a site of α5 function, α5GFP is not detectable in the MHb, and α5 mRNA is expressed there only at very low levels. However,α5GFP is strongly expressed in a subset of neurons in the interpeduncular nucleus (IP), median raphe/paramedian raphe (MnR/PMnR), and dorsal tegmental area (DTg). Double-label fluorescence in situ hybridization reveals that these neurons are exclusively GABAergic. Transgenic and conventional tract tracing show that α5GFP neurons in the IP project principally to theMnR/PMnRand DTg/interfascicular dorsal raphe, both areas rich in serotonergic neurons. Theα5GFP neurons in the IP are located in a region that receives cholinergic fiber inputs from the ventral MHb, and optogenetically assisted circuit mapping demonstrates a monosynaptic connection between these cholinergic neurons and α5GFP IP neurons. Selective inhibitors of both α4β2- and α3β4-containing nicotinic receptors were able to reduce nicotine-evoked inward currents inα5GFP neurons in the IP, suggesting a mixed nicotinic receptor profile in these cells. Together, these findings show that theα5-GABAergic interneurons form a link from the MHb to serotonergic brain centers, which is likely to mediate some of the behavioral effects of nicotine.
- Subjects
NICOTINIC receptors; GABA agents; LABORATORY rodents; CHOLINERGIC receptors; RAPHE nuclei; FLUORESCENCE in situ hybridization
- Publication
Journal of Neuroscience, 2013, Vol 33, Issue 46, p18022
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.2927-13.2013