{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T14:50:23Z","timestamp":1783003823527,"version":"3.54.5"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"NIH","award":["R01DA043982"],"award-info":[{"award-number":["R01DA043982"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biol Sex Differ"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The insular cortex (IC) plays a pivotal role in processing interoceptive and emotional information, offering insights into sex differences in behavior and cognition. The IC comprises two distinct subregions: the anterior insular cortex (aIC), that processes emotional and social signals, and the posterior insular cortex (pIC), specialized in interoception and perception of pain. Pyramidal projection neurons within the IC integrate multimodal sensory inputs, influencing behavior and cognition. Despite previous research focusing on neuronal connectivity and transcriptomics, there has been a gap in understanding pyramidal neurons characteristics across subregions and between sexes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Adult male and female C57Bl\/6J mice were sacrificed and tissue containing the IC was collected for ex vivo slice electrophysiology recordings that examined baseline sex differences in synaptic plasticity and transmission within aIC and pIC subregions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Clear differences emerged between aIC and pIC neurons in both males and females: aIC neurons exhibited distinctive features such as larger size, increased hyperpolarization, and a higher rheobase compared to their pIC counterparts. Furthermore, we observed variations in neuronal excitability linked to sex, with male pIC neurons displaying a greater level of excitability than their female counterparts. We also identified region-specific differences in excitatory and inhibitory synaptic activity and the balance between excitation and inhibition in both male and female mice. Adult females demonstrated greater synaptic strength and maximum response in the aIC compared to the pIC. Lastly, synaptic long-term potentiation occurred in both subregions in males but was specific to the aIC in females.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We conclude that there are sex differences in synaptic plasticity and excitatory transmission in IC subregions, and that distinct properties of IC pyramidal neurons between sexes could contribute to differences in behavior and cognition between males and females.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13293-024-00593-4","type":"journal-article","created":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T07:01:43Z","timestamp":1711954903000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Sexual differences in neuronal and synaptic properties across subregions of the mouse insular cortex"],"prefix":"10.1186","volume":"15","author":[{"given":"Daniela","family":"Iezzi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"C\u00e1ceres-Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Strauss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Chavis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5579-6208","authenticated-orcid":false,"given":"Olivier J.","family":"Manzoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,1]]},"reference":[{"key":"593_CR1","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1097\/WNP.0000000000000377","volume":"34","author":"LQ Uddin","year":"2017","unstructured":"Uddin LQ, Nomi JS, H\u00e9bert-Seropian B, Ghaziri J, Boucher O. Structure and function of the human insula. J Clin Neurophysiol. 2017;34:300\u20136.","journal-title":"J Clin Neurophysiol"},{"issue":"214","key":"593_CR2","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1007\/s00429-010-0251-3","volume":"2010","author":"C Lamm","year":"2010","unstructured":"Lamm C, Singer T. The role of anterior insular cortex in social emotions. Brain Struct Funct. 2010;2010(214):579\u201391.","journal-title":"Brain Struct Funct."},{"key":"593_CR3","doi-asserted-by":"publisher","unstructured":"Pressman P, Rosen HJ. Disorders of frontal lobe function. Neurobiology of brain disorders: biological basis of neurological and psychiatric disorders. Elsevier Inc.; 2015. https:\/\/doi.org\/10.1016\/B978-0-12-398270-4.00033-1.","DOI":"10.1016\/B978-0-12-398270-4.00033-1"},{"key":"593_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-809324-5.06857-7","author":"ET Rolls","year":"2017","unstructured":"Rolls ET. Limbic structures, emotion, and memory. Curated Ref Collect Neurosci Biobehav Psychol. 2017. https:\/\/doi.org\/10.1016\/B978-0-12-809324-5.06857-7.","journal-title":"Curated Ref Collect Neurosci Biobehav Psychol"},{"key":"593_CR5","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.biopsych.2021.09.004","volume":"91","author":"ML Seney","year":"2022","unstructured":"Seney ML, Nestler EJ. Introduction to special issue: insight into sex differences in neuropsychiatric syndromes from transcriptomic analyses. Biol Psychiatry. 2022;91:3\u20135.","journal-title":"Biol Psychiatry"},{"issue":"2","key":"593_CR6","doi-asserted-by":"publisher","first-page":"01","DOI":"10.35946\/arcr.v40.2.01","volume":"40","author":"AM White","year":"2020","unstructured":"White AM. Gender differences in the epidemiology of alcohol use and related harms in the United States. Alcohol Res. 2020;40(2):01.","journal-title":"Alcohol Res."},{"key":"593_CR7","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.cpr.2017.10.012","volume":"66","author":"RK McHugh","year":"2018","unstructured":"McHugh RK, Votaw VR, Sugarman DE, Greenfield SF. Sex and gender differences in substance use disorders. Clin Psychol Rev. 2018;66:12\u201323.","journal-title":"Clin Psychol Rev"},{"key":"593_CR8","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1016\/j.jpsychires.2011.03.006","volume":"45","author":"CP McLean","year":"2011","unstructured":"McLean CP, Asnaani A, Litz BT, Hofmann SG. Gender differences in anxiety disorders: prevalence, course of illness, comorbidity and burden of illness. J Psychiatr Res. 2011;45:1027\u201335.","journal-title":"J Psychiatr Res"},{"key":"593_CR9","first-page":"83","volume":"5","author":"F Bahrami","year":"2011","unstructured":"Bahrami F, Yousefi N. Females are more anxious than males: a metacognitive perspective. Iran J Psychiatry Behav Sci. 2011;5:83.","journal-title":"Iran J Psychiatry Behav Sci"},{"issue":"4","key":"593_CR10","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/s11920-020-1140-y","volume":"22","author":"DM Christiansen","year":"2020","unstructured":"Christiansen DM, Berke ET. Gender- and sex-based contributors to sex differences in PTSD. Curr Psychiatry Rep. 2020;22(4):19.","journal-title":"Curr Psychiatry Rep."},{"key":"593_CR11","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.eurpsy.2007.02.006","volume":"22","author":"M Nagai","year":"2007","unstructured":"Nagai M, Kishi K, Kato S. Insular cortex and neuropsychiatric disorders: a review of recent literature. Eur Psychiatry. 2007;22:387\u201394.","journal-title":"Eur Psychiatry"},{"key":"593_CR12","doi-asserted-by":"publisher","first-page":"94","DOI":"10.3389\/fnana.2019.00094","volume":"13","author":"C Ibrahim","year":"2019","unstructured":"Ibrahim C, Le Foll B, French L. Transcriptomic characterization of the human insular cortex and claustrum. Front Neuroanat. 2019;13:94.","journal-title":"Front Neuroanat."},{"key":"593_CR13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.7554\/eLife.55585","volume":"9","author":"DA Gehrlach","year":"2020","unstructured":"Gehrlach DA, et al. A whole-brain connectivity map of mouse insular cortex. Elife. 2020;9:1\u201378.","journal-title":"Elife"},{"key":"593_CR14","doi-asserted-by":"publisher","first-page":"2194","DOI":"10.1097\/j.pain.0000000000000615","volume":"157","author":"CJ Watson","year":"2016","unstructured":"Watson CJ. Insular balance of glutamatergic and GABAergic signaling modulates pain processing. Pain. 2016;157:2194\u2013207.","journal-title":"Pain"},{"key":"593_CR15","doi-asserted-by":"publisher","first-page":"308","DOI":"10.3389\/fncel.2016.00308","volume":"10","author":"L Bouamrane","year":"2017","unstructured":"Bouamrane L, et al. Reelin-haploinsufficiency disrupts the developmental trajectory of the e\/i balance in the prefrontal cortex. Front Cell Neurosci. 2017;10:308.","journal-title":"Front Cell Neurosci"},{"issue":"493","key":"593_CR16","first-page":"371","volume":"2012","author":"CG Gkogkas","year":"2012","unstructured":"Gkogkas CG, et al. Autism-related deficits via dysregulated eIF4E-dependent translational control. Nature. 2012;2012(493):371\u20137.","journal-title":"Nature"},{"key":"593_CR17","doi-asserted-by":"publisher","first-page":"3330","DOI":"10.1152\/jn.00397.2007","volume":"98","author":"AM Hattox","year":"2007","unstructured":"Hattox AM, Nelson SB. Layer V neurons in mouse cortex projecting to different targets have distinct physiological properties. J Neurophysiol. 2007;98:3330\u201340.","journal-title":"J Neurophysiol"},{"key":"593_CR18","doi-asserted-by":"publisher","first-page":"3894","DOI":"10.1523\/JNEUROSCI.17-10-03894.1997","volume":"17","author":"B Cauli","year":"1997","unstructured":"Cauli B, et al. Molecular and physiological diversity of cortical nonpyramidal cells. J Neurosci. 1997;17:3894\u2013906.","journal-title":"J Neurosci"},{"key":"593_CR19","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1016\/S0896-6273(00)80479-1","volume":"20","author":"P Parra","year":"1998","unstructured":"Parra P, Guly\u00e1s AI, Miles R. How many subtypes of inhibitory cells in the hippocampus? Neuron. 1998;20:983\u201393.","journal-title":"Neuron"},{"key":"593_CR20","doi-asserted-by":"publisher","first-page":"5555","DOI":"10.1073\/pnas.0601261103","volume":"103","author":"ML Molineux","year":"2006","unstructured":"Molineux ML, et al. Specific T-type calcium channel isoforms are associated with distinct burst phenotypes in deep cerebellar nuclear neurons. Proc Natl Acad Sci U S A. 2006;103:5555\u201360.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"593_CR21","doi-asserted-by":"publisher","first-page":"37","DOI":"10.3389\/fncir.2018.00037","volume":"12","author":"BR Ferguson","year":"2018","unstructured":"Ferguson BR, Gao WJ. PV interneurons: critical regulators of E\/I balance for prefrontal cortex-dependent behavior and psychiatric disorders. Front Neural Circuits. 2018;12:37.","journal-title":"Front Neural Circuits."},{"key":"593_CR22","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/j.tins.2018.07.015","volume":"41","author":"JA Cardin","year":"2018","unstructured":"Cardin JA. Inhibitory interneurons regulate temporal precision and correlations in cortical circuits. Trends Neurosci. 2018;41:689\u2013700.","journal-title":"Trends Neurosci"},{"key":"593_CR23","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.brainres.2019.04.005","volume":"1717","author":"Z Wang","year":"2019","unstructured":"Wang Z, Guo Y, Mayer EA, Holschneider DP. Sex differences in insular functional connectivity in response to noxious visceral stimulation in rats. Brain Res. 2019;1717:15\u201326.","journal-title":"Brain Res"},{"issue":"1","key":"593_CR24","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s10194-018-0849-z","volume":"19","author":"YJ Dai","year":"2018","unstructured":"Dai YJ, Zhang X, Yang Y, Nan HY, Yu Y, Sun Q, Yan LF, Hu B, Zhang J, Qiu ZY, Gao Y, Cui GB, Chen BL, Wang W. Gender differences in functional connectivities between insular subdivisions and selective pain-related brain structures. J Headache Pain. 2018;19(1):24.","journal-title":"J. Headache Pain."},{"key":"593_CR25","doi-asserted-by":"publisher","first-page":"44","DOI":"10.2174\/1876386301710010044","volume":"10","author":"HG Eltumi","year":"2017","unstructured":"Eltumi HG, Tashani OA. Effect of age, sex and gender on pain sensitivity: a narrative review. Open Pain J. 2017;10:44\u201355.","journal-title":"Open Pain J"},{"key":"593_CR26","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1093\/scan\/nst030","volume":"9","author":"Y Moriguchi","year":"2014","unstructured":"Moriguchi Y, Touroutoglou A, Dickerson BC, Barrett LF. Sex differences in the neural correlates of affective experience. Soc Cogn Affect Neurosci. 2014;9:591\u2013600.","journal-title":"Soc Cogn Affect Neurosci"}],"container-title":["Biology of Sex Differences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13293-024-00593-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13293-024-00593-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13293-024-00593-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T07:09:27Z","timestamp":1711955367000},"score":1,"resource":{"primary":{"URL":"https:\/\/bsd.biomedcentral.com\/articles\/10.1186\/s13293-024-00593-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,1]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["593"],"URL":"https:\/\/doi.org\/10.1186\/s13293-024-00593-4","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-3431502\/v1","asserted-by":"object"},{"id-type":"doi","id":"10.1101\/2023.10.18.562844","asserted-by":"object"}]},"ISSN":["2042-6410"],"issn-type":[{"value":"2042-6410","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,1]]},"assertion":[{"value":"11 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 February 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Animals were treated in compliance with the European Communities Council Directive (86\/609\/EEC) and the United States National Institutes of Health Guide for the care and use of laboratory animals. All procedures using experimental animals were approved by Aix-Marseille University Institutional Animal Care & Use Committee.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors read and approved the final manuscript for publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"29"}}