Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus

NEUROTROPHINS promote neuronal survival and differentiation, but the fact that their expression is modified by neuronal activity, suggests a role in regulating synapse development and plasticity(1-3). In developing hippocampus, the expression of brain-derived neurotrophic factor (BDNF) and its receptor TrkB(4-7) increases in parallel with the ability to undergo long-term potentiation (LTP)(8-10). Here me report a mechanism by which BDNF modulates hippocampal LTP. Exogenous BDNF promoted the induction of LTP by tetanic stimulation in young (postnatal day 12-13) hippocampal slices, which in the absence of BDNF show only short-term potentiation (STP), This effect was due to an enhanced ability of hippocampal synapses to respond to tetanic stimulation, rather than to a direct modulation of the LTP-triggering mechanism. A TrkB-IgG fusion protein, which scavenges endogenous BDNF11, reduced the synaptic responses to tetanus as well as the magnitude of LTP in adult hippocampus.