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Cited by 136Nicotinic Acetylcholine Receptors StudySmoking Behavior and CessationNeuroscience and Neuropharmacology Research

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

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Shih, Pei-Yu, Engle, Staci E., Oh, Gyeon, Deshpande, Purnima, Puskar, Nyssa L., Lester, Henry A., Drenan, Ryan M.·2014·The Journal of Neuroscience
DOI 10.1523/jneurosci.0476-14.2014PMC PMC4099552
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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 μ m 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mice that underwent withdrawal from chronic nicotine were less responsive to nicotine application compared with mice withdrawn from chronic saline.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.

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  • Electrophysiological studies show that α3 and β4 levels are strong throughout the ventral MHb, while α6, β2, β3, and α4 subunits are selectively found in some but not all of these neurons.

    “Electrophysiological studies have shown that, whereas α3 and β4 nAChR subunit levels are strong throughout the ventral MHb, α6, β2, β3, and α4 subunits are selectively found in some, but not all of these neurons (Shih et al. 2014).”

    From Mechanisms of Nicotine Addiction (2021) · cites this paper as Shih et al. 2014

    The Results report strong, even α3 and β4 localization throughout ventral MHb and regional differences for α4, α6, β2, and β3. But β2 immunoreactivity is reported throughout ventral MHb, and β3 is weak—not absent—in its lateral portion, so the claim that each is found in some but not all of these neurons overstates the evidence. The subunit-localization findings came from staining, although the study also used electrophysiology. (LLM, conf=0.86)

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References 54 · Cited by 136

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Authors
Shih, P.-Y., Engle, S. E., Oh, G., Deshpande, P., Puskar, N. L., Lester, H. A., & Drenan, R. M.
Affiliations
  • Purdue University West Lafayette (US)
  • California Institute of Technology (US)
ORCID
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
2014-07-16
Volume
34
Issue
29
Pages
9789-9802
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.0476-14.2014
PMC
PMC4099552
OpenAlex
W2048729105
Cited by
136
References
54
Citations by year
2026: 9 · 2025: 13 · 2024: 6 · 2023: 9 · 2022: 7 · 2021: 7 · 2020: 13 · 2019: 16 · 2018: 18 · 2017: 11 · 2016: 15 · 2015: 9 · 2014: 3
FWCI
5.20
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion, cc-by-nc-sa)
Funders
  • National Institutes of Health
  • National Institute on Drug Abuse (RC2DA028955, DA028955, DA030396, K99DA030396, R00DA030396)
  • National Institute of Neurological Disorders and Stroke (R01NS034407, NS034407, R37NS034407)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
nicotinic acetylcholine receptors, medial habenula, interpeduncular nucleus, choline acetyltransferase, nicotine withdrawal
MeSH terms
Animals, Choline O-Acetyltransferase, Dose-Response Relationship, Drug, Electric Stimulation, Female, Male, Membrane Potentials, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Nicotine, Receptors, Nicotinic, Gene Expression, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid, Patch-Clamp Techniques, Excitatory Amino Acid Agents, Habenula, Protein Subunits, Green Fluorescent Proteins, Mice, In Vitro Techniques

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