The role of brain-derived neurotrophic factor receptors in the mature hippocampus: Modulation of long-term potentiation through a presynaptic mechanism involving TrkB

The neurotrophin BDNF has been shown to modulate long-term potentiation (LT P) at Schaffer collateral-CA1 hippocampal synapses. Mutants in the BDNF rec eptor gene trkB and antibodies to its second receptor p75NTR have been used to determine the receptors and cells involved in this response. Inhibition of p75NTR does not detectably reduce LTP or affect presynaptic function, b ut analyses of newly generated trkB mutants implicate TrkB. One mutant has reduced expression in a normal pattern of TrkB throughout the brain. The se cond mutant was created by cre-loxP-mediated removal of TrkB in CA1 pyramid al neurons of this mouse. Neither mutant detectably impacts survival or mor phology of hippocampal neurons. TrkB reduction, however, affects presynapti c function and reduces the ability of tetanic stimulation to induce LTP. Po stsynaptic glutamate receptors are not affected by TrkB reduction, indicati ng that BDNF does not modulate plasticity through postsynaptic TrkB. Consis tent with this, elimination of TrkB in postsynaptic neurons does not affect LTP. Moreover, normal LTP is generated in the mutant with reduced TrkB by a depolarization-low-frequency stimulation pairing protocol that puts minim al demands on presynaptic terminal function. Thus, BDNF appears to act thro ugh TrkB presynaptically, but not postsynaptically, to modulate LTP.