Production of brain-derived neurotrophic factor gates plasticity in developing visual cortex

We have previously shown that recovery of visual responses to a deprived eye during the critical period in mouse primary visual cortex (V1) requires both export of mRNA encoding brain derived neurotrophic factor (BDNF) to the dendrites of cortical cells (Kaneko et al., 2012) and phosphorylation of the TrkB receptor for BDNF (Kaneko et al., 2008a). TrkB phosphorylation is not required for the loss of response during monocular deprivation (MD). Studies in vitro show that formation of new connections requires BDNF (Meyer-Franke et al., 1995, 1998; Gottmann et al., 2009). We have now studied the temporal relationship between the production of mature BDNF and the recovery of visual responses. Visual cortical responses to an eye whose vision has been occluded for several days during the critical period and is then re-opened recovers rapidly during binocular vision or more slowly following reverse occlusion, when the previously intact fellow eye is occluded in a model of "patch therapy" for amblyopia. The time to recovery of visual responses differed by 18 hours between these two procedures, but in each the production of mature BDNF preceded the recovery by 6 hours. These findings suggest that a spurt of BDNF secretion stimulates the growth of connections serving the deprived eye to restore visual responses. Significance StatementBy demonstrating that BDNF production precedes rather than merely accompanies the increase in cortical responses, we provide further evidence that BDNF production plays a causal role, thereby gating the plasticity that underlies the recovery of visual cortex from monocular deprivation.