Long-term potentiation in the dentate gyrus of the rat hippocampus is accompanied by brain-derived neurotrophic factor-induced activation of TrkB

A role for neurotrophic factors, in particular brain-derived neurotrophic f actor (BDNF), in modulating synaptic plasticity in the adult brain:has been described in recent years by several laboratories. A great deal of emphasi s has been placed on establishing its precise role in the expression of lon g-term potentiation (LTP) in the hippocampus. Here we attempt to address th is question by investigating, first, its release following induction of LTP in perforant path-granule cell synapses and, second; the signalling events which follow activation of the BDNF receptor, TrkB, in the presynaptic ter minal. We report that BDNF release is increased from slices of dentate gyru s following tetanic stimulation of the perforant path and that TrkB activat ion is increased in synaptosomes prepared from tetanized dentate gyrus. The se changes are accompanied by increased activation of one member of the fam ily of mitogen-activated protein kinases, extracellular signal-regulated ki nase (ERK) and the data indicate that these events play a role in modulatin g release of glutamate from perforant path-granule cell synapses, because t he Trk inhibitor K252a and the ERK inhibitor, UO126, both inhibited the BDN F-induced enhancement of release. We propose that the increase in phosphory lation of the transcription factor cAMP response element binding protein an d in protein synthesis might underlie the more persistent components of LTP in dentate gyrus.