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Differential Expression and Function of Nicotinic Acetylcholine Receptors in Subdivisions of Medial Habenula

Shih, Pei-Yu and Engle, Staci E. and Oh, Gyeon and Deshpande, Purnima and Puskar, Nyssa L. and Lester, Henry A. and Drenan, Ryan M. (2014) Differential Expression and Function of Nicotinic Acetylcholine Receptors in Subdivisions of Medial Habenula. Journal of Neuroscience, 34 (29). pp. 9789-9802. ISSN 0270-6474. PMCID PMC4099552. doi:10.1523/JNEUROSCI.0476-14.2014.

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Neuronal nAChRs in the medial habenula (MHb) to the interpeduncular nucleus (IPN) pathway are key mediators of nicotine's aversive properties. In this paper, we report new details regarding nAChR anatomical localization and function in MHb and IPN. A new group of knock-in mice were created that each expresses a single nAChR subunit fused to GFP, allowing high-resolution mapping. We find that α3 and β4 nAChR subunit levels are strong throughout the ventral MHb (MHbV). In contrast, α6, β2, β3, and α4 subunits are selectively found in some, but not all, areas of MHbV. All subunits were found in both ChAT-positive and ChAT-negative cells in MHbV. Next, we examined functional properties of neurons in the lateral and central part of MHbV (MHbVL and MHbVC) using brain slice patch-clamp recordings. MHbVL neurons were more excitable than MHbVC neurons, and they also responded more strongly to puffs of nicotine. In addition, we studied firing responses of MHbVL and MHbVC neurons in response to bath-applied nicotine. Cells in MHbVL, but not those in MHbVC, increased their firing substantially in response to 1 μm nicotine. Additionally, MHbVL neurons from mice that underwent withdrawal from chronic nicotine were less responsive to nicotine application compared with mice withdrawn from chronic saline. Last, we characterized rostral and dorsomedial IPN neurons that receive input from MHbVL axons. Together, our data provide new details regarding neurophysiology and nAChR localization and function in cells within the MHbV.

Item Type:Article
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URLURL TypeDescription CentralArticle
Lester, Henry A.0000-0002-5470-5255
Drenan, Ryan M.0000-0002-8141-8577
Additional Information:© 2014 The Authors. The authors grant the Society for Neuroscience an exclusive license to publish their work for the first 6 months. After 6 months the work becomes available to the public to copy, distribute, or display under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license. Received Jan. 31, 2014; revised June 9, 2014; accepted June 12, 2014. This work was supported by a Brain and Behavior Research Foundation (formerly National Alliance for Research on Schizophrenia and Depression) Young Investigator Award and National Institutes of Health Grant DA030396 to R.M.D., Grant DA028955 to H.A.L. and Michael J. Marks, and Grant NS034407 to Dennis A. Dougherty). We thank Elisha Mackey and Rahul Srinivasan for technical assistance.
Funding AgencyGrant Number
Brain and Behavior Research FoundationUNSPECIFIED
Subject Keywords:habenula; interpeduncular; nicotine; nicotinic; tobacco; withdrawal
Issue or Number:29
PubMed Central ID:PMC4099552
Record Number:CaltechAUTHORS:20140814-112513666
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Official Citation:Shih, P.-Y., Engle, S. E., Oh, G., Deshpande, P., Puskar, N. L., Lester, H. A., & Drenan, R. M. (2014). Differential Expression and Function of Nicotinic Acetylcholine Receptors in Subdivisions of Medial Habenula. The Journal of Neuroscience, 34(29), 9789-9802. doi: 10.1523/jneurosci.0476-14.2014
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:48559
Deposited By: Jason Perez
Deposited On:14 Aug 2014 20:30
Last Modified:10 Nov 2021 18:32

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