{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T15:14:01Z","timestamp":1782227641499,"version":"3.54.5"},"posted":{"date-parts":[[2024,3,4]]},"group-title":"Neuroscience","reference-count":75,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,4,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Dysfunction of the cortico-basal circuitry \u2013 including its primary input nucleus, the striatum \u2013 contributes to neuropsychiatric disorders, including autism and Tourette Syndrome (TS). These conditions show marked sex differences, occurring more often in males than in females. Regulatory interneurons, including cholinergic interneurons (CINs) and parvalbumin-expressing GABAergic fast spiking interneurons (FSIs), are implicated in human neuropsychiatric disorders such as TS, and ablation of these interneurons produces relevant behavioral pathology in male mice, but not in females. Here we investigate sex differences in the density and distribution of striatal interneurons, using stereological quantification of CINs, FSIs, and somatostatin-expressing (SOM) GABAergic interneurons in the dorsal striatum (caudate-putamen) and the ventral striatum (nucleus accumbens) in male and female mice. Males have a higher density of CINs than females, especially in the dorsal striatum; females have equal distribution between dorsal and ventral striatum. FSIs showed similar effects, with a greater dorsal-ventral density gradient in males than in females. SOM interneurons were denser in the ventral than in the dorsal striatum, with no sex differences. These sex differences in the density and distribution of FSIs and CINs may contribute to sex differences in basal ganglia function, including in the context of psychopathology.<\/jats:p>","DOI":"10.1101\/2024.02.29.582798","type":"posted-content","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T04:16:00Z","timestamp":1709525760000},"source":"Crossref","is-referenced-by-count":5,"title":["Sex differences in the distribution and density of regulatory interneurons in the striatum"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2019-1628","authenticated-orcid":false,"given":"Meghan","family":"Van Zandt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deirdre","family":"Flanagan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2117-9321","authenticated-orcid":false,"given":"Christopher","family":"Pittenger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024041103200908000_2024.02.29.582798v2.1","doi-asserted-by":"crossref","unstructured":"Adler, A. , Katabi, S. , Finkes, I. , Prut, Y. & Bergman, H. (2013) Different correlation patterns of cholinergic and GABAergic interneurons with striatal projection neurons. Frontiers in Systems Neuroscience, 7.","DOI":"10.3389\/fnsys.2013.00047"},{"key":"2024041103200908000_2024.02.29.582798v2.2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2012-1458"},{"key":"2024041103200908000_2024.02.29.582798v2.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2016.04.023"},{"key":"2024041103200908000_2024.02.29.582798v2.4","doi-asserted-by":"crossref","unstructured":"Aziz, H. C. & Mangieri, R. A. (2023) Sexually dimorphic characteristics of dopamine D1 receptor-expressing neurons within the shell of the nucleus accumbens of adolescent mice. Res Sq.","DOI":"10.21203\/rs.3.rs-3717874\/v1"},{"issue":"5","key":"2024041103200908000_2024.02.29.582798v2.5","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1177\/1073858418824256","article-title":"The Striatum\u2019s Role in Executing Rational and Irrational Economic Behaviors","volume":"25","year":"2019","journal-title":"The Neuroscientist"},{"key":"2024041103200908000_2024.02.29.582798v2.6","doi-asserted-by":"publisher","DOI":"10.1016\/0166-4328(86)90044-6"},{"key":"2024041103200908000_2024.02.29.582798v2.7","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)90471-5"},{"issue":"12","key":"2024041103200908000_2024.02.29.582798v2.8","doi-asserted-by":"crossref","first-page":"5007","DOI":"10.1038\/s41380-022-01880-5","article-title":"Mispatterning and interneuron deficit in Tourette Syndrome basal ganglia organoids","volume":"27","year":"2022","journal-title":"Molecular Psychiatry"},{"key":"2024041103200908000_2024.02.29.582798v2.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2012.05.011"},{"key":"2024041103200908000_2024.02.29.582798v2.10","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13877"},{"key":"2024041103200908000_2024.02.29.582798v2.11","doi-asserted-by":"crossref","first-page":"173","DOI":"10.3389\/fendo.2018.00173","article-title":"Sex Differences in Medium Spiny Neuron Excitability and Glutamatergic Synaptic Input: Heterogeneity Across Striatal Regions and Evidence for Estradiol-Dependent Sexual Differentiation","volume":"9","year":"2018","journal-title":"Frontiers in Endocrinology"},{"key":"2024041103200908000_2024.02.29.582798v2.12","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)91225-H"},{"key":"2024041103200908000_2024.02.29.582798v2.13","doi-asserted-by":"crossref","unstructured":"Cattaneo, S. , Zaghi, M. , Maddalena, R. , Bedogni, F. , Sessa, A. & Taverna, S. (2019) Somatostatin-Expressing Interneurons Co-Release GABA and Glutamate onto Different Postsynaptic Targets in the Striatum. bioRxiv, 566984.","DOI":"10.1101\/566984"},{"key":"2024041103200908000_2024.02.29.582798v2.14","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(92)90830-3"},{"issue":"7979","key":"2024041103200908000_2024.02.29.582798v2.15","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41586-023-06492-9","article-title":"Dopamine and glutamate regulate striatal acetylcholine in decision-making","volume":"621","year":"2023","journal-title":"Nature"},{"key":"2024041103200908000_2024.02.29.582798v2.16","doi-asserted-by":"crossref","unstructured":"Chen, J. , Tian, C. , Zhang, Q. , Xiang, H. , Wang, R. , Hu, X. & Zeng, X. (2022) Changes in Volume of Subregions Within Basal Ganglia in Obsessive\u2013Compulsive Disorder: A Study With Atlas-Based and VBM Methods. Frontiers in Neuroscience, 16.","DOI":"10.3389\/fnins.2022.890616"},{"issue":"1","key":"2024041103200908000_2024.02.29.582798v2.17","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1046\/j.1471-4159.1994.62010070.x","article-title":"GABAergic Modulation of Striatal Cholinergic Interneurons: An In Vivo Microdialysis Study","volume":"62","year":"1994","journal-title":"Journal of Neurochemistry"},{"key":"2024041103200908000_2024.02.29.582798v2.18","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1432.010"},{"issue":"7","key":"2024041103200908000_2024.02.29.582798v2.19","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1111\/ejn.14670","article-title":"Activation of parvalbumin-expressing neurons reconfigures neuronal ensembles in murine striatal microcircuits","volume":"53","year":"2021","journal-title":"European Journal of Neuroscience"},{"key":"2024041103200908000_2024.02.29.582798v2.20","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0466-16.2016"},{"key":"2024041103200908000_2024.02.29.582798v2.21","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22279"},{"key":"2024041103200908000_2024.02.29.582798v2.22","unstructured":"Franklin, K. B. J. & Paxinos, G. (1997) The mouse brain in stereotaxic coordinates. Translated from eng by. San Diego: Academic Press San Diego."},{"issue":"6","key":"2024041103200908000_2024.02.29.582798v2.23","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1111\/ejn.14581","article-title":"Ablation of striatal somatostatin interneurons affects MSN morphology and electrophysiological properties, and increases cocaine-induced hyperlocomotion in mice","volume":"51","year":"2020","journal-title":"Eur J Neurosci"},{"key":"2024041103200908000_2024.02.29.582798v2.24","doi-asserted-by":"crossref","unstructured":"Gerfen, C. R. & Wilson, C. J. (1996) Chapter II The basal ganglia, Handbook of chemical neuroanatomy Elsevier, 371-468.","DOI":"10.1016\/S0924-8196(96)80004-2"},{"key":"2024041103200908000_2024.02.29.582798v2.25","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-5846(97)00158-9"},{"key":"2024041103200908000_2024.02.29.582798v2.26","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3875-11.2011"},{"key":"2024041103200908000_2024.02.29.582798v2.27","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4870-09.2010"},{"key":"2024041103200908000_2024.02.29.582798v2.28","doi-asserted-by":"publisher","DOI":"10.1126\/science.8091209"},{"key":"2024041103200908000_2024.02.29.582798v2.29","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a021691"},{"key":"2024041103200908000_2024.02.29.582798v2.30","doi-asserted-by":"publisher","DOI":"10.1038\/S41593-019-0341-3"},{"key":"2024041103200908000_2024.02.29.582798v2.31","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702934"},{"key":"2024041103200908000_2024.02.29.582798v2.32","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.44903"},{"key":"2024041103200908000_2024.02.29.582798v2.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2011.04.004"},{"key":"2024041103200908000_2024.02.29.582798v2.34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0502624102"},{"key":"2024041103200908000_2024.02.29.582798v2.35","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22206"},{"key":"2024041103200908000_2024.02.29.582798v2.36","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-0102(96)01134-0"},{"key":"2024041103200908000_2024.02.29.582798v2.37","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(95)98374-8"},{"issue":"4","key":"2024041103200908000_2024.02.29.582798v2.38","doi-asserted-by":"crossref","first-page":"111531","DOI":"10.1016\/j.celrep.2022.111531","article-title":"Cholinergic control of striatal GABAergic microcircuits","volume":"41","year":"2022","journal-title":"Cell Rep"},{"key":"2024041103200908000_2024.02.29.582798v2.39","doi-asserted-by":"publisher","DOI":"10.1038\/8138"},{"key":"2024041103200908000_2024.02.29.582798v2.40","first-page":"993552","article-title":"17\u03b2-estradiol does not have a direct effect on the function of striatal cholinergic interneurons in adult mice in vitro","volume":"13","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2024041103200908000_2024.02.29.582798v2.41","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.051508.135422"},{"issue":"6","key":"2024041103200908000_2024.02.29.582798v2.42","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1016\/j.neuron.2017.02.033","article-title":"Parvalbumin Interneurons Modulate Striatal Output and Enhance Performance during Associative Learning","volume":"93","year":"2017","journal-title":"Neuron"},{"key":"2024041103200908000_2024.02.29.582798v2.43","doi-asserted-by":"publisher","DOI":"10.1016\/J.BIOPSYCH.2014.07.018"},{"key":"2024041103200908000_2024.02.29.582798v2.44","doi-asserted-by":"crossref","unstructured":"Lim, S. A. O. , Kang, U. J. & McGehee, D. S. (2014) Striatal cholinergic interneuron regulation and circuit effects. Frontiers in Synaptic Neuroscience, 6.","DOI":"10.3389\/fnsyn.2014.00022"},{"key":"2024041103200908000_2024.02.29.582798v2.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaac.2017.03.013"},{"key":"2024041103200908000_2024.02.29.582798v2.46","doi-asserted-by":"publisher","DOI":"10.1111\/pcn.12830"},{"key":"2024041103200908000_2024.02.29.582798v2.47","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-16-06063.2000"},{"key":"2024041103200908000_2024.02.29.582798v2.48","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/B978-0-12-411546-0.00009-3","article-title":"Neuroendocrine aspects of Tourette syndrome","volume":"112","year":"2013","journal-title":"Int Rev Neurobiol"},{"key":"2024041103200908000_2024.02.29.582798v2.49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0157682"},{"key":"2024041103200908000_2024.02.29.582798v2.50","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00507.2005"},{"issue":"8","key":"2024041103200908000_2024.02.29.582798v2.51","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1016\/j.celrep.2018.07.053","article-title":"Diversity of Interneurons in the Dorsal Striatum Revealed by Single-Cell RNA Sequencing and PatchSeq","volume":"24","year":"2018","journal-title":"Cell Reports"},{"key":"2024041103200908000_2024.02.29.582798v2.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.01.023"},{"key":"2024041103200908000_2024.02.29.582798v2.53","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.250795"},{"key":"2024041103200908000_2024.02.29.582798v2.54","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3709-06.2007"},{"key":"2024041103200908000_2024.02.29.582798v2.55","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3177-09.2009"},{"key":"2024041103200908000_2024.02.29.582798v2.56","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-014-0794-9"},{"key":"2024041103200908000_2024.02.29.582798v2.57","doi-asserted-by":"publisher","DOI":"10.1016\/0165-3806(89)90142-9"},{"key":"2024041103200908000_2024.02.29.582798v2.58","doi-asserted-by":"crossref","unstructured":"Poppi, L. A. , Ho-Nguyen, K. T. , Shi, A. , Daut, C. T. & Tischfield, M. A. (2021) Recurrent Implication of Striatal Cholinergic Interneurons in a Range of Neurodevelopmental, Neurodegenerative, and Neuropsychiatric Disorders. Cells, 10(4).","DOI":"10.3390\/cells10040907"},{"key":"2024041103200908000_2024.02.29.582798v2.59","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00263.2018"},{"key":"2024041103200908000_2024.02.29.582798v2.60","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2017.05.004"},{"key":"2024041103200908000_2024.02.29.582798v2.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2017.01.020"},{"key":"2024041103200908000_2024.02.29.582798v2.62","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.21283"},{"issue":"4","key":"2024041103200908000_2024.02.29.582798v2.63","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.jocrd.2014.06.002","article-title":"The Prevalence of Tic Disorders and Clinical Characteristics in Children","volume":"3","year":"2014","journal-title":"J Obsessive Compuls Relat Disord"},{"issue":"7","key":"2024041103200908000_2024.02.29.582798v2.64","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","year":"2012","journal-title":"Nature Methods"},{"key":"2024041103200908000_2024.02.29.582798v2.65","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-010-0284-7"},{"issue":"3","key":"2024041103200908000_2024.02.29.582798v2.66","first-page":"378","article-title":"Distinct regions of the striatum underlying effort, movement initiation and effort discounting","volume":"5","year":"2021","journal-title":"Nature Human Behaviour"},{"key":"2024041103200908000_2024.02.29.582798v2.67","doi-asserted-by":"publisher","DOI":"10.1017\/S0140525X00047488"},{"key":"2024041103200908000_2024.02.29.582798v2.68","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.04.038"},{"key":"2024041103200908000_2024.02.29.582798v2.69","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(99)00500-X"},{"key":"2024041103200908000_2024.02.29.582798v2.70","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)02135-1"},{"key":"2024041103200908000_2024.02.29.582798v2.71","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(94)90510-X"},{"key":"2024041103200908000_2024.02.29.582798v2.72","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2018.04.002"},{"key":"2024041103200908000_2024.02.29.582798v2.73","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3064-16.2017"},{"key":"2024041103200908000_2024.02.29.582798v2.74","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-020-00915-1"},{"key":"2024041103200908000_2024.02.29.582798v2.75","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(03)02801-4"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.02.29.582798","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T06:02:14Z","timestamp":1768456934000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.02.29.582798"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,4]]},"references-count":75,"URL":"https:\/\/doi.org\/10.1101\/2024.02.29.582798","relation":{},"subject":[],"published":{"date-parts":[[2024,3,4]]},"subtype":"preprint"}}