BDNF modulates contextual fear learning during adolescence.

TitleBDNF modulates contextual fear learning during adolescence.
Publication TypeJournal Article
Year of Publication2014
AuthorsDincheva I, Pattwell SS, Tessarollo L, Bath KG, Lee FS
JournalDev Neurosci
Date Published2014
KeywordsAging, Animals, Brain-Derived Neurotrophic Factor, Fear, Glyceraldehyde-3-Phosphate Dehydrogenases, Hippocampus, Learning, Male, Mice, Mice, Knockout, Polymorphism, Single Nucleotide, Receptor, trkB

Brain-derived neurotrophic factor (BDNF) is a growth factor that plays key roles in regulating higher-order emotional and cognitive processes including fear learning and memory. A common single-nucleotide polymorphism (SNP) has been identified in the human BDNF gene (BDNF Val66Met) that leads to decreased BDNF secretion and impairments in specific forms of fear learning in adult humans and genetically modified mice containing this SNP. As the emergence of anxiety and other fear-related disorders peaks during adolescence, we sought to better understand the impact of this BDNF SNP on fear learning during the transition through adolescence in BDNF Val66Met knock-in mice. Previously, we have shown that contextual fear expression is temporarily suppressed in wild-type mice during a distinct period in adolescence, but re-emerges at later, postadolescent ages. Until recently, it was unclear whether BDNF-TrkB signaling is involved in the modulation of hippocampal-dependent contextual fear learning and memory during this adolescent period. Here we show that in BDNF Val66Met mice, the presence of the Met allele does not alter contextual fear expression during adolescence, but when previously conditioned BDNF(Met/Met) mice are tested in adulthood, they fail to display the delayed expression of contextual fear compared to wild-type BDNF(Val/Val) controls, indicating that the Met allele may permanently alter hippocampal function, leading to persistent functioning that is indistinguishable from the adolescent state. Conversely, truncated TrkB receptor (TrkB.T1)-deficient (TrkB.T1(-/-)) mice, a genetic mouse model with increased BDNF-TrkB signaling through full-length TrkB receptors, exhibit an accelerated expression of contextual fear during adolescence compared to wild-type controls. Our results point to a critical function for BDNF-TrkB signaling in fear regulation in vivo, particularly during a potentially sensitive period in adolescence.

Alternate JournalDev. Neurosci.
PubMed ID24992985
PubMed Central IDPMC4150737
Grant ListMH079513 / MH / NIMH NIH HHS / United States
P50 MH079513 / MH / NIMH NIH HHS / United States
HD055177 / HD / NICHD NIH HHS / United States
R01 NS052819 / NS / NINDS NIH HHS / United States
NS052819 / NS / NINDS NIH HHS / United States
T32 HD055177 / HD / NICHD NIH HHS / United States