A caged Ab reveals an immediate/instructive effect of BDNF during hippocampal synaptic potentiation

Neurotrophins have been shown to be involved in functional strengthening of central nervous system synapses. Although their general importance in this process is undisputed, it remains unresolved whether neurotrophins are tru ly mediators of synaptic strengthening or merely important cofactors. To ad dress this question, we have devised a method to inactivate endogenous brai n-derived neurotrophic factor (BDNF) with high time resolution by "caging" a function-blocking mAb against BDNF with a photosensitive protecting compo und. Different assays were used to show that this inactivation of the Ab is reversible by UV light. Synaptic potentiation after tau -burst stimulation in the CA1 region of acute hippocampal slices was significantly less when applying the unmodified Ab compared with the caged Ab. Importantly, photoac tivation of the caged Ab during the time of induction of synaptic enhanceme nt led to a marked decrease in potentiation. Our experiments therefore stre ngthen the view that endogenous BDNF has fast effects during induction of s ynaptic plasticity. The results additionally show that caged Abs can provid e a tool for precise spatiotemporal control over endogenous protein levels.