Modulation of neuronal calcium signaling by neurotrophic factors

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin (NT) family, is emerging as a key mediator of activity-dependent modifications of synaptic strength in the central nervous system. Because of the well-established role of post-synaptic elevations in concentrations of free Ca(2+) ions ([Ca(2+)](i)) in synaptic plasticity, we investigated the hypothesis that BDNF exerts its neuromodulatory effects on hippocampal pyramidal neurons by enhancing dendritic [Ca(2+)](i) transients mediated by voltage-dependent Ca(2+) channels (VDCCs) during the firing of back-propagating action potentials. Simultaneous whole-cell recording and microfluorometric Ca(2+) imaging were performed in CA1 pyramidal neurons from hippocampal organotypic slice cultures treated with BDNF for 2-4 days in vitro. Our observations indicate that long-term exposure to BDNF does not affect [Ca(2+)](i) transients in apical dendrites mediated by influx through L-type VDCCs during trains of back-propagating action potentials evoked by direct depolarizing current injections. These results suggest that, despite BDNF's profound effects on hippocampal synaptic plasticity, and of L-type Ca(2+) channels on neuronal gene transcription, the role of BDNF in cellular models of hippocampus-dependent learning and memory does not involve modulation of voltage-gated dendritic Ca(2+) signaling mediated by L-type channels in apical dendrites of CA1 pyramidal neurons.