BDNF-induced BDNF release mediates presynaptic LTP and is regulated by cannabinoids

Abstract

AbstractAlthough 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.HighlightsPre- and postsynaptic BDNF are both required for presynaptic LTP in the dentate gyrusBDNF is released from MC axons and GC proximal dendrites following repetitive activation of MC axonsPresynaptic BDNF release is inhibited by activation of CB1R expressed on MC axonsBDNF is sufficient to trigger postsynaptic BDNF release from GCs in a TrkB- and calcium-dependent mannerEnriched environment induces BDNF-dependent LTP of MC-GC synapses in vivoIn BriefBerthoux et al. describe a novel mechanism of presynaptic LTP that requires BDNF-induced BDNF release. This BDNF-mediated plasticity can occur in vivo and is tightly controlled by cannabinoid activity.