NEUROTROPHINS AND TIME - DIFFERENT ROLES FOR TRKB SIGNALING IN HIPPOCAMPAL LONG-TERM POTENTIATION

We examined the role of TrkB ligands in hippocampal long-term potentia tion (LTP) using function-blocking TrkB antiserum (Ab) and Trk-IgG fus ion proteins. Incubation of hippocampal slices with TrkB Ab had no eff ect on basal synaptic transmission, short-term plasticity, or LTP indu ced by several trains of tetanic stimulation. The TrkB Ab-treated slic es, however, showed significant deficits in LTP induced by either thet a-burst stimulation (TBS) or ''pairing.'' Slices exposed to the same n umber of inducing stimuli, delivered either as TBS or as a single 100 Hz epoch, only exhibited TrkB-sensitive LTP when TBS was used, indicat ing that the temporal pattern of stimulation determines the neurotroph in dependence. The late phase of LTP (2-3 hr) was also significantly i mpaired in slices pretreated with TrkB Ab or a TrkB-IgG. The applicati on of a TrkB-IgG 30 min after LTP induction caused previously potentia ted synaptic transmission to return to baseline levels, indicating tha t TrkB ligands are required to maintain LTP for up to 1 hr after induc tion. Taken together, these results indicate that both the temporal pa tterns of synaptic activity and the different temporal phases of synap tic enhancement are important in determining the neurotrophin dependen ce of plasticity in the hippocampus.