EXPRESSION OF A DOMINANT-NEGATIVE TRKB RECEPTOR, T1, REVEALS A REQUIREMENT FOR PRESYNAPTIC SIGNALING IN BDNF-INDUCED SYNAPTIC POTENTIATION IN CULTURED HIPPOCAMPAL-NEURONS

We have developed a method to analyze the relative contributions of pr e- and postsynaptic actions of a particular gene product in neurons in culture and potentially in slices using adenovirus-mediated gene tran sfer. A recombinant virus directed the expression of both a GFP report er protein and TrkB.T1, a C-terminal truncated dominant negative TrkB neurotrophin receptor. When expressed in the presynaptic cell at synap ses between embryonic hippocampal neurons in culture, the dominant neg ative TrkB.T1 inhibited two forms of synaptic potentiation induced by the neurotrophin brain-derived neurotrophic factor (BDNF): (i) greater evoked synaptic transmission and (ii) higher frequency of spontaneous miniature synaptic currents. These inhibition effects are not seen if the transgene is expressed only in the postsynaptic cell. We conclude that BDNF-TrkB signal transduction in the presynaptic terminal leads to both types of potentiation and is therefore the primary cause of sy naptic enhancement by BDNF in these neurons.