GABAergic synapse maturation: evidence of the instructive role of activity-dependent BDNF release.

摘要

The study of the actions of brain-derived neurotrophic factor (BDNF) on central neurons and their synapses has revealed a constellation of observations ranging from neuronal survival and differentiation during early development to rapid effects on membrane conductance and intra-cellular Ca~(2+) levels in mature neurons (Amaral et al. 2007). Unfortunately, most studies in this abundant 'BDNF literature' are phenomenological and lack mechanistic insights, and even more importantly, direct evidence that the endogenous - native - protein is able to trigger an effect similar to that produced by application of recombinant BDNF. In addition, a few studies of BDNF actions generated long-standing controversial argumentations. Luckily, other BDNF effects have been consistently replicated, such as its role in the developmental maturation of GABAergic synapses. The paper by Kuczewski et al. (2008) in this issue of The Journal of Physiology presents direct evidence that endogenously released BDNF plays an instructive role in a new form of GABAergic synaptic plasticity in area CA3 of the neonatal hippocampus. The fact that BDNF was necessary for the maturation of GABAergic synapses was known from studies in the cortex oi Bdnf overexpressing mice (Huang et al. 1999), but its source and mechanism of activity-dependent release remained unexplored. Now, a series of rigorous experiments provide solid evidence that glutamatergic activity causes Ca~(2+)-dependent release of BDNF from postsynaptic CA3 neuron dendrites, which leads to an enduring potentiation of GABA_A R-mediated synaptic currents.