title: 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mice that underwent withdrawal from chronic nicotine were less responsive to nicotine application compared with mice withdrawn from chronic saline.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.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907, and.
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Shih
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907, and.
authors.forename: Staci E
authors.initials: SE
authors.lastname: Engle
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907, and.
authors.forename: Gyeon
authors.initials: G
authors.lastname: Oh
authors.affiliation: Division of Biology and Biological Engineering and.
authors.forename: Purnima
authors.initials: P
authors.lastname: Deshpande
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125.
authors.forename: Nyssa L
authors.initials: NL
authors.lastname: Puskar
authors.affiliation: Division of Biology and Biological Engineering and.
authors.forename: Henry A
authors.initials: HA
authors.lastname: Lester
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907, and drenan@purdue.edu.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Drenan
mesh_terms: D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics; D019262:Habenula / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D018683:Excitatory Amino Acid Agents; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D049452:Green Fluorescent Proteins; D009538:Nicotine; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D002795:Choline O-Acetyltransferase
keywords: habenula; interpeduncular; nicotine; nicotinic; tobacco; withdrawal