BDNF-induced BDNF release mediates presynaptic LTP and is regulated by cannabinoids
Although brain-derived neurotrophic factor (BDNF) and its effector, Tropomyosin receptor kinase B (TrkB), are implicated in activity-dependent synaptic plasticity, the precise underlying mechanisms remain unclear. In the dentate gyrus, a hippocampal input region that expresses uniquely high levels of BDNF, repetitive activation of mossy cells (MCs) induces a presynaptic, BDNF/TrkB-dependent form of LTP at MC to granule cell (GC) synapses. Here, we report that activity-induced BDNF release from MC axons in mice elicits postsynaptic BDNF release in a TrkB- and calcium-dependent manner, and that BDNF-induced BDNF release is essential for LTP induction. Suppression of BDNF release by tonic and phasic activity of presynaptic type-1 cannabinoid receptors dampened LTP, revealing an unprecedented role of these receptors in controlling neuropeptide release. Lastly, BDNF-mediated MC-GC LTP can be elicited in vivo. Thus, BDNF-induced BDNF release emerges as a mechanism for activity-dependent LTP that may contribute to dentate gyrus-dependent learning, epilepsy, and neuropsychiatric disorders.