Hippocampal long-term potentiation is supported by presynaptic and postsynaptic tyrosine receptor kinase B-mediated phospholipase Cgamma signaling.

Neurotrophins have been shown to play a critical role in activity-dependent synaptic plasticity such as long-term potentiation (LTP) in the hippocampus. Although the role of brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor [tyrosine receptor kinase B (TrkB)] is well documented, it still remains unresolved whether presynaptic or postsynaptic activation of TrkB is involved in the induction of LTP. To address this question, we locally and specifically interfered with a downstream target of the TrkB receptor, phospholipase Cγ (PLCγ). We prevented PLCγ signaling by overexpression of the PLCγ pleckstrin homology (PH) domain with a Sindbis virus vector. The isolated PH domain has an inhibitory effect and thereby blocks endogenous PLCγ signaling and consequently also IP 3 production. Surprisingly, concurrent presynaptic and postsynaptic blockade of PLCγ signaling was required to reduce LTP to levels comparable with those in TrkB and BDNF knock-out mice. Blockade of presynaptic or postsynaptic signaling alone did not result in a significant reduction of LTP.