{ "abstract": "Nicotinic acetylcholine signaling modulates dopaminergic output in mammalian midbrain circuits and can thereby influence decision-making. In Drosophila, dopamine neurons (DANs) in the protocerebral anterior medial (PAM) cluster convey sugar reward signals and promote approach toward a rewarded odor after associative learning. Although nicotinic acetylcholine receptors (nAChRs) have been implicated in regulating PAM DAN excitability and transmitter release, how this modulation supports specific cognitive operations during learning and memory remains unclear. Here, we tested the role of nAChRs in PAM DANs in odor–sugar associative learning and memory. Among nine nAChR genes examined, loss of the nicotinic acetylcholine receptor α1 subunit (Dα1) in PAM neurons impaired appetitive memory. Consistent with this requirement, Dα1 was detected in these DANs at both the transcript and protein levels, with Dα1 puncta observed in PAM axon-terminal and putative dendritic regions. Importantly, live imaging showed that Dα1 knockdown in PAM DANs attenuated odor-evoked synaptic Caa2+ signals, whereas sugar-evoked Ca2+ responses were largely preserved. Behaviorally, Dα1 knockdown in PAM DANs reduced performance in a two-odor forced-choice discrimination task, whereas no performance deficit was detected across the single-odor pursuit conditions or innate odor choice. Together, these results identify a nicotinic mechanism in PAM DANs that supports odor-evoked synaptic activity and contributes to learned odor-choice performance when competing odor cues are present. Author summary: Acetylcholine (ACh) and dopamine (DA) are crucial neurotransmitters that form an important axis for cognitive functions. Understanding their roles in decision-making is of utmost interest, as alterations in this axis are linked to the pathophysiology of psychiatric disorders, including nicotine addiction and schizophrenia. This study focuses on the nicotinic acetylcholine receptor, specifically the Drosophila α1 (Dα1) subunit found in rewarding dopamine neurons of fruit flies. Disrupting Dα1 reduced odor-evoked synaptic activity in reward-related dopamine neurons and impaired learned odor choice when flies were required to choose between competing odors. These findings indicate a vital role for Dα1 in reward circuits that support value-based decision-making and provide a tractable model of the ACh-DA axis for linking cellular actions to behavior.", "abstract_shown": true, "affiliations": [ "Graduate School of Engineering Science, Akita University, Akita, Japan", "Graduate School of Life Sciences, Tohoku University, Sendai, Japan", "Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai, Japan", "Information Education Center, Shokei Gakuin University, Natori, Japan" ], "article_type": "Research Article", "arxiv": null, "author_total": 10, "authors": [ { "affs": [ 0 ], "name": "Nobuhiro Yamagata" }, { "affs": [ 1 ], "name": "Nobuhiro Takahashi" }, { "affs": [ 2 ], "name": "Rino Ichikawa" }, { "affs": [ 3 ], "name": "Eru Wada" }, { "name": "Momo Murakami" }, { "name": "Ayako Abe" }, { "name": "Mai Kanno" }, { "name": "Toshiharu Ichinose" }, { "name": "Norihiro Katayama" }, { "name": "Hiromu Tanimoto" } ], "bibtex": "https://research.draconitic.com/paper/5xbjhcf29j9dx.bib", "cited_by": 0, "doi": "10.1371/journal.pgen.1012356", "fulltext_url": "https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012356", "id": "5xbjhcf29j9dx", "issns": [ "1553-7404" ], "landing_url": "https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012356", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "plos", "/Biology and life sciences/Anatomy/Nervous system/Synapses" ], [ "plos", "/Biology and life sciences/Biochemistry/Hormones/Catecholamines/Dopamine" ], [ "plos", "/Biology and life sciences/Biochemistry/Neurochemistry/Neurotransmitters/Biogenic amines/Catecholamines/Dopamine" ], [ "plos", "/Biology and life sciences/Biochemistry/Neurochemistry/Neurotransmitters/Cholinergics" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/Transmembrane receptors/Acetylcholine receptors/Nicotinic acetylcholine receptors" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Neurons" ], [ "plos", "/Biology and life sciences/Cell biology/Signal transduction/Transmembrane receptors/Acetylcholine receptors/Nicotinic acetylcholine receptors" ], [ "plos", "/Biology and life sciences/Neuroscience/Cellular neuroscience/Neurons" ], [ "plos", "/Biology and life sciences/Neuroscience/Cognitive science/Cognition/Decision making" ], [ "plos", "/Biology and life sciences/Neuroscience/Cognitive science/Cognition/Memory" ], [ "plos", "/Biology and life sciences/Neuroscience/Cognitive science/Cognitive psychology/Decision making" ], [ "plos", "/Biology and life sciences/Neuroscience/Cognitive science/Cognitive psychology/Learning" ], [ "plos", "/Biology and life sciences/Neuroscience/Learning and memory/Learning" ], [ "plos", "/Biology and life sciences/Neuroscience/Learning and memory/Memory" ], [ "plos", "/Biology and life sciences/Neuroscience/Neurochemistry/Neurotransmitters/Biogenic amines/Catecholamines/Dopamine" ], [ "plos", "/Biology and life sciences/Neuroscience/Neurochemistry/Neurotransmitters/Cholinergics" ], [ "plos", "/Biology and life sciences/Neuroscience/Neurophysiology/Synapses" ], [ "plos", "/Biology and life sciences/Physiology/Electrophysiology/Neurophysiology/Synapses" ], [ "plos", "/Biology and life sciences/Psychology/Cognitive psychology/Decision making" ], [ "plos", "/Biology and life sciences/Psychology/Cognitive psychology/Learning" ], [ "plos", "/Medicine and health sciences/Anatomy/Nervous system/Synapses" ], [ "plos", "/Physical sciences/Chemistry/Chemical compounds/Organic compounds/Amines/Catecholamines/Dopamine" ], [ "plos", "/Physical sciences/Chemistry/Organic chemistry/Organic compounds/Amines/Catecholamines/Dopamine" ], [ "plos", "/Social sciences/Psychology/Cognitive psychology/Decision making" ], [ "plos", "/Social sciences/Psychology/Cognitive psychology/Learning" ] ], "openalex": null, "pdf_url": "https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1012356&type=printable", "pmcid": null, "pmid": null, "published": "2026-10-29", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/5xbjhcf29j9dx.ris", "sources": [ { "first_seen": "2026-10-30T12:17:17Z", "native_id": "10.1371/journal.pgen.1012356", "source": "plos", "url": "https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012356" } ], "subjects": [ { "field": "biology", "origin": "plos:neuroscience", "subfield": "neuroscience" } ], "title": "Nicotinic receptor in dopamine neurons mediates learned odor choice", "title_text": "Nicotinic receptor in dopamine neurons mediates learned odor choice", "type": "peer-reviewed", "updated_at": "2026-10-31T12:20:55Z", "url": "https://research.draconitic.com/paper/5xbjhcf29j9dx", "venue": "PLOS Genetics", "versions": [] }