Conclusions: In addition to its strong presynaptic actions on quantal neurotransmitter release, the regulation of the spatial and temporal patterns of postsynaptic Ca2+ elevations by BDNF is also a likely mechanism for its modulation of synaptic plasticity. The intracellular signaling cascades activated by TrkB receptors include several well-characterized protein kinases that target most of the routes of Ca2+ entry into hippocampal neurons. In addition, TrkB activation leads to IP3 formation, strongly arguing for direct Ca2+ mobilization from intracellular Ca2+ stores. Lastly, depletion of intracellular Ca2+ stores is associated with the activation of plasma membrane non-selective cationic currents thought to mediate Ca2+ store refilling. These membrane currents mediated by members of the TRPC family of ion channels not only represent novel downstream effects of neurotrophin action, but also are intriguing points of convergence with other intracellular signaling cascades, such as those triggered by group-I metabotropic glutamate receptors. The information gained from future experiments in this rapidly evolving field will integrate the actions of BDNF at synapses with the requirement of dendritic Ca2+ signals necessary for the induction of synaptic plasticity. Ultimately, the challenge ahead is to assimilate the varied functional and structural consequences of BDNF signaling through TrkB receptors at both sides of the synaptic cleft at excitatory synapses in the hippocampus with its intriguing role in the consolidation of hippocampal-dependent learning. Indeed, BDNF represents the prototypical example of a consolidation factor necessary for trans-synaptic plasticity at hippocampal synapses.