{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T02:36:07Z","timestamp":1794537367402,"version":"4.9.1"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T00:00:00Z","timestamp":1697068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>The medial amygdala (MeA) is a sexually dimorphic brain region that regulates fear responses, emotional memories, and social behaviors. It is known to be larger and contains more cells in males. The MeA integrates information through input connections from olfactory regions, bed nucleus of the stria terminalis, ventral hippocampus, and thalamic and hypothalamic structures. We hypothesize that in addition to the size differences, there are differences in regional connectivity between the sexes. In this study, we utilized G-deleted rabies monosynaptic retrograde tracing to compare amygdala presynaptic cells in male and female whole mouse brains. We report differences in connection patterns to the amygdala, with higher overall connectivity (presynaptic per starter) in males and a larger fraction of inputs originating from the bed nucleus of the stria terminalis, lateral septum, and medial preoptic area. Furthermore, we examined input connections to the orbital cortex (ORB), a brain region shown to be larger in volume in females, and found the opposite trend, where females had more total inputs. Together, our findings extend the evidence for sexual dimorphism in the brain to the neuronal wiring pattern, with likely impacts on behavior and disease susceptibility.<\/jats:p>","DOI":"10.3389\/fnins.2023.1258284","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T11:44:10Z","timestamp":1697111050000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Sexual dimorphism in synaptic inputs to the mouse amygdala and orbital cortex"],"prefix":"10.3389","volume":"17","author":[{"given":"Etay","family":"Aloni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Tibi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Hochgerner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Zeisel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,12]]},"reference":[{"key":"B1","unstructured":"Mouse Brain2023"},{"key":"B2","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1016\/j.neuroimage.2013.07.040","article-title":"Sex differences in the development of brain mechanisms for processing biological motion","volume":"83","author":"Anderson","year":"2013","journal-title":"Neuroimage"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1007\/s00429-014-0954-y","article-title":"Afferent projections to the different medial amygdala subdivisions: a retrograde tracing study in the mouse","volume":"221","author":"C\u00e1diz-Moretti","year":"2016","journal-title":"Brain Struct. Funct"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1016\/j.cell.2019.01.024","article-title":"Sexually dimorphic control of parenting behavior by the medial amygdala","volume":"176","author":"Chen","year":"2019","journal-title":"Cell"},{"key":"B5","doi-asserted-by":"publisher","first-page":"10759","DOI":"10.1523\/JNEUROSCI.2919-05.2005","article-title":"Sexually dimorphic synaptic organization of the medial amygdala","volume":"25","author":"Cooke","year":"2005","journal-title":"J. Neurosci"},{"key":"B6","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/npp.2009.109","article-title":"Phasic vs. sustained fear in rats and humans: role of the extended amygdala in fear vs. anxiety","volume":"35","author":"Davis","year":"2010","journal-title":"Neuropsychopharmacology"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13293-022-00448-w","article-title":"Sex differences in the human brain: a roadmap for more careful analysis and interpretation of a biological reality","volume":"13","author":"DeCasien","year":"2022","journal-title":"Biol. Sex Differ"},{"key":"B8","unstructured":"Sex-, strain and lateral differences in brain cytoarchitecture across a large mouse population\n            ElkindD.\n            HochgernerH.\n            AloniE.\n            ShentalN.\n            ZeiselA.\n          37144870Elife2023"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1007\/s12264-020-00545-z","article-title":"Whole-brain map of long-range monosynaptic inputs to different cell types in the amygdala of the mouse","volume":"36","author":"Fu","year":"2020","journal-title":"Neurosci. Bull"},{"key":"B10","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1093\/cercor\/11.6.490","article-title":"Normal sexual dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging","volume":"11","author":"Goldstein","year":"2001","journal-title":"Cereb. Cortex"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15475","article-title":"Prevalence of sexual dimorphism in mammalian phenotypic traits","author":"Karp","year":"2017","journal-title":"Nat. Commun"},{"key":"B12","doi-asserted-by":"publisher","first-page":"8699","DOI":"10.1523\/JNEUROSCI.1176-14.2014","article-title":"Functional properties and projections of neurons in the medial amygdala","volume":"34","author":"Keshavarzi","year":"2014","journal-title":"J. Neurosci"},{"key":"B13","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1038\/mp.2016.1","article-title":"Overshadowed by the amygdala: the bed nucleus of the stria terminalis emerges as key to psychiatric disorders","volume":"21","author":"Lebow","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-018-38239-2","article-title":"Novel findings from 2,838 adult brains on sex differences in gray matter brain volume","volume":"9","author":"Lotze","year":"2019","journal-title":"Sci. Rep"},{"key":"B15","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1016\/j.psyneuen.2012.09.018","article-title":"Oxytocin mediates rodent social memory within the lateral septum and the medial amygdala depending on the relevance of the social stimulus : male juvenile vs. female adult conspecifics","volume":"38","author":"Lukas","year":"2013","journal-title":"Psychoneuroendocrinology"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1523\/ENEURO.0035-20.2020","article-title":"Sex differences in biophysical signatures across molecularly definedmedial amygdala neuronal subpopulations","volume":"7","author":"Matos","year":"2020","journal-title":"eNeuro"},{"key":"B17","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.tins.2021.10.010","article-title":"Neurobiology of the lateral septum: regulation of social behavior","volume":"45","author":"Menon","year":"2021","journal-title":"Trends Neurosci"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-815134-1.00002-7","article-title":"Structure and function of the medial amygdala. 1st ed","author":"Petrulis","year":"2020","journal-title":"Handb. Behav. Neurosci"},{"key":"B19","doi-asserted-by":"publisher","first-page":"2492","DOI":"10.1002\/cne.23964","article-title":"Sex and laterality differences in medial amygdala neurons and astrocytes of adult mice","volume":"524","author":"Pfau","year":"2016","journal-title":"J. Comp. Neurol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1002\/cne.902460304","article-title":"The organization of neural inputs to the medial preoptic nucleus of the rat","volume":"246","author":"Simerly","year":"1986","journal-title":"J. Comp. Neurol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1126\/science.3992248","article-title":"Sexually dimorphic","volume":"228","year":"1984","journal-title":"Science"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02648-0","article-title":"Medial preoptic area in mice is capable of mediating sexually dimorphic behaviors regardless of gender","author":"Wei","year":"2018","journal-title":"Nat. Commun"},{"key":"B23","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1016\/j.cell.2011.12.018","article-title":"Modular genetic control of sexually dimorphic behaviors","volume":"148","author":"Xu","year":"2011","journal-title":"Cell"},{"key":"B24","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/0306-4530(94)90033-7","article-title":"Sexually dimorphic cell groups in the medial preoptic area that are essential for male sex behavior and the neural pathways needed for their effects","volume":"19","author":"Yahr","year":"1994","journal-title":"Psychoneuroendocrinology"}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2023.1258284\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T11:44:15Z","timestamp":1697111055000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2023.1258284\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,12]]},"references-count":24,"alternative-id":["10.3389\/fnins.2023.1258284"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2023.1258284","relation":{"has-part":[{"id-type":"doi","id":"https:\/\/doi.org\/10.3389\/fnins.2023.1258284.s001","asserted-by":"subject"},{"id-type":"doi","id":"https:\/\/doi.org\/10.3389\/fnins.2023.1258284.s002","asserted-by":"subject"},{"id-type":"doi","id":"https:\/\/doi.org\/10.3389\/fnins.2023.1258284.s003","asserted-by":"subject"},{"id-type":"doi","id":"https:\/\/doi.org\/10.3389\/fnins.2023.1258284.s004","asserted-by":"subject"},{"id-type":"doi","id":"https:\/\/doi.org\/10.3389\/fnins.2023.1258284.s005","asserted-by":"subject"},{"id-type":"doi","id":"https:\/\/doi.org\/10.3389\/fnins.2023.1258284.s006","asserted-by":"subject"},{"id-type":"doi","id":"https:\/\/doi.org\/10.3389\/fnins.2023.1258284.s007","asserted-by":"subject"}]},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,12]]},"article-number":"1258284"}}