The Role of BDNF in the Development of Fear Learning

Abstract

Brain-derived neurotrophic factor (BDNF) is a growth factor that is dynamically expressed in the brain across postnatal development, regulating neuronal differentiation and synaptic plasticity. The neurotrophic hypothesis of psychiatric mood disorders postulates that in the adult brain, decreased BDNF levels leads to altered neural plasticity, contributing to disease. Although BDNF has been established as a key factor regulating the critical period plasticity in the developing visual system, it has recently been shown to also play a role in fear circuitry maturation, which has implications for the emergence of fear-related mood disorders. This review provides a detailed overview of developmental changes in expression of BDNF isoforms, as well as their receptors across postnatal life. In addition, recent developmental studies utilizing a genetic BDNF single nucleotide polymorphism (Val66Met) knock-in mouse highlight the impact of BDNF on fear learning during a sensitive period spanning the transition into adolescent time frame. We hypothesize that BDNF in the developing brain regulates fear circuit plasticity during a sensitive period in early adolescence, and alterations in BDNF expression (genetic or environmental) have a persistent impact on fear behavior and fear-related disorders.

Intrauterine exposure to maternal stress alters Bdnf IV DNA methylation and telomere length in the brain of adult rat offspring

“…Nonetheless, data altogether are consistent with the notion that stress experienced by the dam is able to produce long-term epigenetic changes in offspring at a gene well-linked to neuroplasticity and cognition (e.g. Bekinschtein et al, 2008;Dincheva et al, 2016;Martinowich et al, 2007;McEwen et al, 2015) and mental health (e.g. Fuchikami et al, 2011;Keller et al, 2010;Perroud et al, 2013;Smith et al, 2011).…”

BDNF controls cognitive processes related to neuropsychiatric manifestations via autophagic regulation of p62 and GABAA receptor trafficking

“…Animal models with reduced BDNF expression or activity showed disturbances of neurotransmission or neural plasticity, which likely underlie cognitive deficits observed in these models (Dincheva et al, 2012;Lu et al, 2014;Dincheva et al, 2016), consistent with a dimensional contribution of this pathway in cognitive symptoms across a range of psychiatric disorders.…”

Stress Aggravates High-Fat-Diet-Induced Insulin Resistance via a Mechanism That Involves the Amygdala and Is Associated with Changes in Neuroplasticity

“…These proteins were selected for the following reasons. BDNF-TrkB signaling is involved in the chronic stress-induced neuroadaptation in the amygdala and the pathogenesis of depression [19,20], SYT-1 and SYT-4 are members of vSNAREs with SYT-1 being calcium-dependent and located in the presynaptic regions, and SYT-4 is calcium-independent and dominantly expressed in the postsynaptic regions [21,22]. SNAP-25 is a member of tSNAREs involved in regulating the release of neurotransmitters [23,24], and these SNARE proteins play crucial roles in mediating synaptic behaviors and plasticity [25,26].…”