Impaired Fear Extinction Recall in Serotonin Transporter Knockout Rats Is Transiently Alleviated during Adolescence

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 gene variance affects fear-driven beha...

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Published in:	Brain sciences Vol. 9; no. 5; p. 118
Main Authors:	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
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 22-05-2019 MDPI
Subjects:	adolescence Adolescents Adults Affective disorders age Amygdala Anxiety BDNF Behavior Brain-derived neurotrophic factor c-Fos protein Child development Cognition & reasoning Emotions Fear & phobias Fear conditioning fear extinction Gene expression Glutamic acid receptors (ionotropic) Hypotheses Immunoreactivity medial prefrontal cortex N-Methyl-D-aspartic acid receptors Neurotransmission NMDA Polymerase chain reaction Prefrontal cortex rat Serotonin Serotonin transporter Stress Teenagers medial prefrontal cortex rat BDNF serotonin transporter fear extinction NMDA adolescence age
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Summary:	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 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2076-3425 2076-3425
DOI:	10.3390/brainsci9050118