Impaired fear extinction recall in serotonin transporter knockout rats is transiently alleviated during adolescence
Articolo
Data di Pubblicazione:
2019
Citazione:
Impaired fear extinction recall in serotonin transporter knockout rats is transiently alleviated during adolescence / P. Schipper, P. Brivio, D.D. Leest, L. Madder, B. Asrar, F. Rebuglio, M.M.M. Verheij, T. Kozicz, M.A. Riva, F. Calabrese, M.J.A.G. Henckens, J.R. Homberg. - In: BRAIN SCIENCES. - ISSN 2076-3425. - 9:5(2019 May), pp. 118.1-118.19. [10.3390/brainsci9050118]
Abstract:
Adolescence is a developmental phase characterized by emotional turmoil and coincides with the emergence of affective disorders. Inherited serotonin transporter (5-HTT) downregulation in humans increases sensitivity to these disorders. To reveal whether and how 5-HTT gene variance affects fear-driven behavior in adolescence, we tested wildtype and serotonin transporter knockout (5-HTT-/-) rats of preadolescent, adolescent, and adult age for cued fear extinction and extinction recall. To analyze neural circuit function, we quantified inhibitory synaptic contacts and, through RT-PCR, the expression of c-Fos, brain-derived neurotrophic factor (BDNF), and NDMA receptor subunits, in the medial prefrontal cortex (mPFC) and amygdala. Remarkably, the impaired recall of conditioned fear that characterizes preadolescent and adult 5-HTT-/- rats was transiently normalized during adolescence. This did not relate to altered inhibitory neurotransmission, since mPFC inhibitory immunoreactivity was reduced in 5-HTT-/- rats across all ages and unaffected in the amygdala. Rather, since mPFC (but not amygdala) c-Fos expression and NMDA receptor subunit 1 expression were reduced in 5-HTT-/- rats during adolescence, and since PFC c-Fos correlated negatively with fear extinction recall, the temporary normalization of fear extinction during adolescence could relate to altered plasticity in the developing mPFC.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Adolescence; Age; BDNF; Fear extinction; Medial prefrontal cortex; NMDA; Rat; Serotonin transporte
Elenco autori:
P. Schipper, P. Brivio, D.D. Leest, L. Madder, B. Asrar, F. Rebuglio, M.M.M. Verheij, T. Kozicz, M.A. Riva, F. Calabrese, M.J.A.G. Henckens, J.R. Homberg
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