Impaired Fear Extinction Recall in Serotonin Transporter Knockout Rats Is Transiently Alleviated during Adolescence
AbstractAdolescence 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. View Full-Text
- Supplementary File 1:
PDF-Document (PDF, 616 KB)
Share & Cite This Article
Schipper, P.; Brivio, P.; de Leest, D.; Madder, L.; Asrar, B.; Rebuglio, F.; Verheij, M.M.M.; Kozicz, T.; Riva, M.A.; Calabrese, F.; Henckens, M.J.A.G.; Homberg, J.R. Impaired Fear Extinction Recall in Serotonin Transporter Knockout Rats Is Transiently Alleviated during Adolescence. Brain Sci. 2019, 9, 118.
Schipper P, Brivio P, de Leest D, Madder L, Asrar B, Rebuglio F, Verheij MMM, Kozicz T, Riva MA, Calabrese F, Henckens MJAG, Homberg JR. Impaired Fear Extinction Recall in Serotonin Transporter Knockout Rats Is Transiently Alleviated during Adolescence. Brain Sciences. 2019; 9(5):118.Chicago/Turabian Style
Schipper, Pieter; Brivio, Paola; de Leest, David; Madder, Leonie; Asrar, Beenish; Rebuglio, Federica; Verheij, Michel M.M.; Kozicz, Tamas; Riva, Marco A.; Calabrese, Francesca; Henckens, Marloes J.A.G.; Homberg, Judith R. 2019. "Impaired Fear Extinction Recall in Serotonin Transporter Knockout Rats Is Transiently Alleviated during Adolescence." Brain Sci. 9, no. 5: 118.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.