ArticleProceedings of the National Academy of Sciences of the United States of America2013
Reexposure to nicotine during withdrawal increases the pacemaking activity of cholinergic habenular neurons.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 105 citations in OpenAlex.
- Asymmetrical modulation of fear expression via GABAProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review: "The Disappointment Dilemma: Short- and Long-Term Learning From Negative Outcomes".The European journal of neuroscience · 2026Review
- Negative correlation between habenular volume and duration of gambling disorder: Modulation by symptom severity and personality traits.Journal of behavioral addictions · 2026Article
- Nicotinic Receptors in the Medial Habenula to Interpeduncular Nucleus Pathway: Modulators of Reward, Aversion and Emotion.The European journal of neuroscience · 2025Review
- Article
- Nicotine Reprograms Aging-Related Metabolism and Protects Against Motor Decline in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Complex opioid driven modulation of glutamatergic and cholinergic neurotransmission in a GABAergic brain nucleus associated with emotion, reward and addiction.bioRxiv : the preprint server for biology · 2025Article
- Calcium-activated ion channels drive atypical inhibition in medial habenula neurons.Science advances · 2025Article
- Abundant extrasynaptic expression of α3β4-containing nicotinic acetylcholine receptors in the medial habenula-interpeduncular nucleus pathway in mice.Scientific reports · 2024Article
- Article
- STZ-induced hyperglycemia differentially influences mitochondrial distribution and morphology in the habenulointerpeduncular circuit.Frontiers in cellular neuroscience · 2024Article
- Extracellular ATP Neurotransmission and Nicotine Sex-Specifically Modulate Habenular Neuronal Activity in Adolescence.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Article
- New medications development for smoking cessation.Addiction neuroscience · 2023Article
- Understanding the habenula: A major node in circuits regulating emotion and motivation.Pharmacological research · 2023Review
- Article
- Chronic exposure to cigarette smoke extract increases nicotine withdrawal symptoms in adult and adolescent male rats.Advances in drug and alcohol research · 2023Article
- Hedgehog-interacting protein acts in the habenula to regulate nicotine intake.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Neurobiological Mechanisms of Nicotine Reward and Aversion.Pharmacological reviews · 2022Review
- Role of endocannabinoid signaling in a septohabenular pathway in the regulation of anxiety- and depressive-like behavior.Molecular psychiatry · 2021Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The discovery of genetic variants in the cholinergic receptor nicotinic CHRNA5-CHRNA3-CHRNB4 gene cluster associated with heavy smoking and higher relapse risk has led to the identification of the midbrain habenula-interpeduncular axis as a critical relay circuit in the control of nicotine dependence. Although clear roles for α3, β4, and α5 receptors in nicotine aversion and withdrawal have been established, the cellular and molecular mechanisms that participate in signaling nicotine use and contribute to relapse have not been identified. Here, using translating ribosome affinity purification (TRAP) profiling, electrophysiology, and behavior, we demonstrate that cholinergic neurons, but not peptidergic neurons, of the medial habenula (MHb) display spontaneous tonic firing of 2-10 Hz generated by hyperpolarization-activated cyclic nucleotide-gated (HCN) pacemaker channels and that infusion of the HCN pacemaker antagonist ZD7288 in the habenula precipitates somatic and affective signs of withdrawal. Further, we show that a strong, α3β4-dependent increase in firing frequency is observed in these pacemaker neurons upon acute exposure to nicotine. No change in the basal or nicotine-induced firing was observed in cholinergic MHb neurons from mice chronically treated with nicotine. We observe, however, that, during withdrawal, reexposure to nicotine doubles the frequency of pacemaking activity in these neurons. These findings demonstrate that the pacemaking mechanism of cholinergic MHb neurons controls withdrawal, suggesting that the heightened nicotine sensitivity of these neurons during withdrawal may contribute to smoking relapse.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.