BDNF ACUTELY INCREASES TYROSINE PHOSPHORYLATION OF THE NMDA RECEPTOR SUBUNIT 2B IN CORTICAL AND HIPPOCAMPAL POSTSYNAPTIC DENSITIES

While neurotrophins are critical for neuronal survival and differentia tion, recent work suggests that they acutely regulate synaptic transmi ssion as well. Brain-derived neurotrophic factor (BDNF) enhances excit atory postsynaptic currents in cultured dissociated hippocampal neuron s within 2-3 min through postsynaptic, phosphorylation-dependent mecha nisms. Moreover, BDNF modulates hippocampal long-term potentiation, in which postsynaptic NMDA (N-methyl-D-aspartate) receptors (NRs) play a key role. We now report that BDNF acutely increases tyrosine phosphor ylation of the specific NMDA receptor subunit NR2B, which has recently been shown to play a role in long-term potentiation. Incubation of BD NF with cortical or hippocampal postsynaptic densities for 5 min incre ased tyrosine phosphorylation of the NR2B subunits in a dose-dependent manner. A maximal increase to 165% of control phosphorylation occurre d at a BDNF concentration of 2 ng/ml. The BDNF action appeared to be s pecific, since nerve growth factor, another member of the neurotrophin gene family, had no effect on NR2B phosphorylation. Further, BDNF act ion was selective, since it did not alter tyrosine phosphorylation of NR2A subunits. Our results suggest that tyrosine phosphorylation of NR 2B subunits of the NMDA receptor may contribute to neurotrophin modula tion of postsynaptic responsiveness and long-term potentiation. (C) 19 98 Elsevier Science B.V.