{"doi":"10.1111/ejn.16477","title":"Cholinergic interneurons in the nucleus accumbens are a site of cellular convergence for corticotropin‐releasing factor and estrogen regulation in male and female mice","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>\n                    Cholinergic interneurons (ChIs) act as master regulators of striatal output, finely tuning neurotransmission to control motivated behaviours. ChIs are a cellular target of many peptide and hormonal neuromodulators, including corticotropin‐releasing factor, opioids, insulin and leptin, which can influence an animal's behaviour by signalling stress, pleasure, pain and nutritional status. However, little is known about how sex hormones via estrogen receptors influence the function of these other neuromodulators. Here, we performed in situ hybridisation on mouse striatal tissue to characterise the effect of sex and sex hormones on choline acetyltransferase (\n                    <jats:italic>Chat</jats:italic>\n                    ), estrogen receptor alpha (\n                    <jats:italic>Esr1</jats:italic>\n                    ) and corticotropin‐releasing factor type 1 receptor (\n                    <jats:italic>Crhr1</jats:italic>\n                    ) expression. Although we did not detect sex differences in ChAT protein levels in the dorsal striatum or nucleus accumbens, we found that female mice have more\n                    <jats:italic>Chat</jats:italic>\n                    mRNA‐expressing neurons than males in both the dorsal striatum and nucleus accumbens. At the population level, we observed a sexually dimorphic distribution of\n                    <jats:italic>Esr1</jats:italic>\n                    ‐ and\n                    <jats:italic>Crhr1</jats:italic>\n                    ‐expressing ChIs in the ventral striatum that was negatively correlated in intact females, which was abolished by ovariectomy and not present in males. Only in the NAc did we find a significant population of ChIs that co‐express\n                    <jats:italic>Crhr1</jats:italic>\n                    and\n                    <jats:italic>Esr1</jats:italic>\n                    in females and to a lesser extent in males. At the cellular level,\n                    <jats:italic>Crhr1</jats:italic>\n                    and\n                    <jats:italic>Esr1</jats:italic>\n                    transcript levels were negatively correlated only during the estrus phase in females, indicating that changes in sex hormone levels can modulate the interaction between\n                    <jats:italic>Crhr1</jats:italic>\n                    and\n                    <jats:italic>Esr1</jats:italic>\n                    mRNA levels.\n                  </jats:p>","journal":"European Journal of Neuroscience","year":2024,"id":649180,"datarank":0.38474240361923057,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.0,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1245990,"name":"Anna E. Ingebretson","orcid":"0000-0001-8221-3621","position":1,"is_corresponding":false},{"id":1692252,"name":"Eleftheria Vogiatzoglou","orcid":null,"position":2,"is_corresponding":false},{"id":1692254,"name":"Paul G. Mermelstein","orcid":null,"position":3,"is_corresponding":false},{"id":333764,"name":"Julia C. Lemos","orcid":"0000-0002-5442-8876","position":4,"is_corresponding":false},{"id":1692251,"name":"Kendra L. Olson","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Cholinergic interneurons in the nucleus accumbens are a site of cellular convergence for corticotropin‐releasing factor and estrogen regulation in male and female mice","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>\n                    Cholinergic interneurons (ChIs) act as master regulators of striatal output, finely tuning neurotransmission to control motivated behaviours. ChIs are a cellular target of many peptide and hormonal neuromodulators, including corticotropin‐releasing factor, opioids, insulin and leptin, which can influence an animal's behaviour by signalling stress, pleasure, pain and nutritional status. However, little is known about how sex hormones via estrogen receptors influence the function of these other neuromodulators. Here, we performed in situ hybridisation on mouse striatal tissue to characterise the effect of sex and sex hormones on choline acetyltransferase (\n                    <jats:italic>Chat</jats:italic>\n                    ), estrogen receptor alpha (\n                    <jats:italic>Esr1</jats:italic>\n                    ) and corticotropin‐releasing factor type 1 receptor (\n                    <jats:italic>Crhr1</jats:italic>\n                    ) expression. Although we did not detect sex differences in ChAT protein levels in the dorsal striatum or nucleus accumbens, we found that female mice have more\n                    <jats:italic>Chat</jats:italic>\n                    mRNA‐expressing neurons than males in both the dorsal striatum and nucleus accumbens. At the population level, we observed a sexually dimorphic distribution of\n                    <jats:italic>Esr1</jats:italic>\n                    ‐ and\n                    <jats:italic>Crhr1</jats:italic>\n                    ‐expressing ChIs in the ventral striatum that was negatively correlated in intact females, which was abolished by ovariectomy and not present in males. Only in the NAc did we find a significant population of ChIs that co‐express\n                    <jats:italic>Crhr1</jats:italic>\n                    and\n                    <jats:italic>Esr1</jats:italic>\n                    in females and to a lesser extent in males. At the cellular level,\n                    <jats:italic>Crhr1</jats:italic>\n                    and\n                    <jats:italic>Esr1</jats:italic>\n                    transcript levels were negatively correlated only during the estrus phase in females, indicating that changes in sex hormone levels can modulate the interaction between\n                    <jats:italic>Crhr1</jats:italic>\n                    and\n                    <jats:italic>Esr1</jats:italic>\n                    mRNA levels.\n                  </jats:p>","is_dataset_classified":null,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39080914","pmcid":"PMC12348452","openalex_id":"https://openalex.org/W4401194469","authors":[],"funders":[{"funder_name":"National Institute of Mental Health","grant_id":"MH122749","title":null},{"funder_name":"NIMH NIH HHS","grant_id":"R01 MH122749","title":null},{"funder_name":"NIMH NIH HHS","grant_id":"K99 MH109627","title":null},{"funder_name":"K99/R00 Pathway to Independence Award","grant_id":"MH109627","title":null},{"funder_name":"NIMH NIH HHS","grant_id":"R00 MH109627","title":null}],"total_grants":5,"fwci":2.3656,"citation_percentile":0.89680365,"influential_citations":0,"citation_trend":[{"year":2024,"count":3},{"year":2025,"count":5},{"year":2026,"count":3}],"oa_status":"hybrid","license":"cc-by-nc-nd","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/ejn.16477","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/ejn.16477","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/ejn.16477","host_type":"publisher"},{"url":"https://doi.org/10.1111/ejn.16477","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39080914","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12348452","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12348452/pdf/nihms-2093265.pdf","host_type":"repository"}],"fields_of_study":["Stress Responses and Cortisol","Neuroendocrine regulation and behavior","Hormonal Regulation and Hypertension"],"mesh_terms":["CRF Receptor, Type 1","Animals","Choline O-Acetyltransferase","Corticotropin-Releasing Hormone","Estrogens","Female","Interneurons","Male","Mice, Inbred C57BL","Nucleus Accumbens","Ovariectomy","Sex Characteristics","Receptors, Corticotropin-Releasing Hormone","Estrogen Receptor alpha","Mice","Cholinergic Neurons"],"keywords":["Nucleus accumbens","Estrogen","Neuroscience","Cholinergic","Endocrinology","Internal medicine","Nucleus","Biology","Psychology","Central nervous system","Medicine","Corticotropin releasing factor","Estrogen receptors","Cholinergic Interneuron"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Zero hunger"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T03:22:06.051864Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}