DETERMINANTS OF BDNF-INDUCED HIPPOCAMPAL SYNAPTIC PLASTICITY - ROLE OF THE TRK-B RECEPTOR AND THE KINETICS OF NEUROTROPHIN DELIVERY

The neurotrophins are a class of signaling molecules known for their g rowth and survival-promoting activities during neuronal development. R ecent studies suggest that the neurotrophins, including brain-derived neurotrophic factor (BDNF), can also dramatically influence synaptic t ransmission in the adult hippocampus. The experiments described in thi s paper indicate that ability of BDNF to potentiate synaptic transmiss ion in the hippocampus relies on functional Trk B receptors. Moreover, the rate at which BDNF is applied to hippocampal synapses is also a p otent determinant of whether synaptic potentiation will result. Hippoc ampal slices perfused with BDMF at a very slow flow rate (e.g., less t han or equal to 25 ml/hr) did not show synaptic potentiation. Increasi ng the rate of BDNF application resulted in synaptic potentiation in w hich the magnitude and onset kinetics of the potentiation were determi ned by the rate of BDNF delivery. Immunocytochemical analysis of BDNF detected with confocal microscopy confirmed these electrophysiological observations, indicating that the penetration of BDNF into hippocampa l slices is influenced dramatically by the perfusion rate.