BDNF and the developmental onset of contextual and cue-dependent fear in mice.

Society for Neuroscience. 2008.


Many psychiatric disorders originating in childhood and adolescence involve improper regulation of fear. Complimentary human and animal studies have uncovered key brain regions in the acquisition and maintenance of fear learning including the amygdala, hippocampus and prefrontal cortex (PFC). Many of these regions undergo protracted development in humans and are not fully mature until the early twenties. Thus, different brain circuits and mechanisms may be involved in regulating fear responses across development. Brain derived neurotrophic factor (BDNF), a molecule involved in neuronal survival and differentiation, is important for long-term potentiation and memory consolidation. Due its role in learning and memory, BDNF signaling is also important for fear conditioning. In addition to maturational changes in fear circuitry, BDNF levels change dynamically during postnatal development. Male, C57BL/6J mice underwent fear conditioning during several important developmental periods. P29, P39, and P49 mice were used, as these ages have been shown to best approximate human pre-, mid-, and post-adolescence, respectively. A developmental dissociation between contextual and cue-dependent fear was observed in mice, replicating results of previous studies using rats. A delayed developmental onset of contextual fear in mice may be indicative of an immature hippocampal network. BDNF levels, in addition to protracted regional brain maturation, may prove to be a key factor in regulating age- dependent differences in fear expression.