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Genetic and environmental factors during development may predispose to the emergence of FRD at the adult age, but the underlying mechanisms are poorly understood. In the present study, we tested whether a partial knock-down of tuberous sclerosis complex 2 (Tsc2, Tuberin), a risk gene for neurodevelopmental disorders, in the basolateral amygdala (BLA) from adolescence could alter fear-network functionality and create a vulnerability ground to FRD appearance at adulthood. Using bilateral injection of a lentiviral vector expressing a miRNA against Tsc2 in the BLA of early (PN25) or late adolescent (PN50) rats, we show that alteration induced specifically from PN25 resulted in an increased c-Fos activity at adulthood in specific layers of the prelimbic cortex, a resistance to fear extinction and an overgeneralization of fear to a safe, novel stimulus. A developmental dysfunction of the amygdala could thus play a role in the vulnerability to FRD emergence at adulthood. We propose our methodology as an alternative to model the developmental vulnerability to FRD, especially in its comorbidity with TSC2-related autism syndrome.<\/jats:p>","DOI":"10.1093\/cercor\/bhab506","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T20:17:18Z","timestamp":1640031438000},"page":"4619-4639","source":"Crossref","is-referenced-by-count":0,"title":["Disruption of amygdala<i>Tsc2<\/i>in adolescence leads to changed prelimbic cellular activity and generalized fear responses at adulthood in rats"],"prefix":"10.1093","volume":"32","author":[{"given":"Fanny","family":"Joly","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, CNRS, Institut des Neurosciences Paris-Saclay , 91400 Saclay , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pauline","family":"Jeckel","sequence":"additional","affiliation":[{"name":"Natural and Medical Sciences Institute at the University of T\u00fcbingen , 72770 Reutlingen , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Kriebel","sequence":"additional","affiliation":[{"name":"Natural and Medical Sciences Institute at the University of T\u00fcbingen , 72770 Reutlingen , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanket","family":"Raut","sequence":"additional","affiliation":[{"name":"School of Psychological Sciences , College of Health and Medicine, , Launceston TAS 7250 , Australia"},{"name":"University of Tasmania , College of Health and Medicine, , Launceston TAS 7250 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"El Massioui","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, CNRS, Institut des Neurosciences Paris-Saclay , 91400 Saclay , 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