Genetic evidence that brain-derived neurotrophic factor mediates competitive interactions between individual cortical neurons

Abstract

Brain-derived neurotrophic factor (BDNF) is a secreted protein important for development and function of neocortical circuitry. Although it is well established that BDNF contributes to the sculpting of dendrite structure and modulation of synapse strength, the range and directionality of BDNF signaling underlying these functions are incompletely understood. To gain insights into the role of BDNF at the level of individual neurons, we tested the cell-autonomous requirements for Bdnf in visual cortical layer 2/3 neurons. We found that the number of functional Bdnf alleles a neuron carries relative to the prevailing genotype determines its density of dendritic spines, the structures at which most excitatory synapses are made. This requirement for Bdnf exists both during postnatal development and in adulthood, suggesting that the amount of BDNF a neuron is capable of producing determines its success in ongoing competition in the environment of the neocortex. Our results suggest that BDNF may perform a long-sought function for a secreted growth factor in mediating the competitive events that shape individual neurons and their circuits.