Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published July 16, 2014 | Published
Journal Article Open

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

Abstract

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mice that underwent withdrawal from chronic nicotine were less responsive to nicotine application compared with mice withdrawn from chronic saline.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.

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.

Attached Files

Published - 9789.full.pdf

Files

9789.full.pdf
Files (5.6 MB)
Name Size Download all
md5:51b118dc3273303beaba93694ca08024
5.6 MB Preview Download

Additional details

Created:
August 22, 2023
Modified:
October 17, 2023