Journal
JOURNAL OF NEUROSCIENCE
Volume 40, Issue 42, Pages 8070-8087Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2838-19.2020
Keywords
AC/PKA; BDNF; endocannabinoid; endocytosis; exocytosis; retrograde signaling
Categories
Funding
- National Key Research & Development Program of China [2016YFA0100802]
- National Natural Science Foundation of China [31971159, 31570833, 31770902]
- Innovation Program of Shanghai Municipal Education Commission [2019-01-07-00-07-E00041]
- Shanghai Municipal Science and Technology Major Project [2018SHZDZX01]
- ZJLab
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Brain-derived neurotropic factor (BDNF) has been shown to play critical roles in neural development, plasticity, and neurodegenerative diseases. The main function of BDNF in the brain is widely accepted to be synaptic regulation. However, how BDNF modulates synaptic transmission, especially the underlying signaling cascades between presynaptic and postsynaptic neurons, remains controversial. In the present study, we investigated the actions of BDNF at rat calyx-type synapses of either sex by measuring the excitatory postsynaptic current (EPSC) and presynaptic calcium current and capacitance changes. We found that BDNF inhibits the EPSC, presynaptic calcium influx, and exocytosis/endocytosis via activation of the presynaptic cannabinoid Type 1 receptors (CB1Rs). Inhibition of the CB1Rs abolished the BDNF-induced presynaptic inhibition, whereas CB1R agonist mimicked the effect of BDNF. Exploring the underlying signaling cascade, we found that BDNF specifically activates the postsynaptic TrkB receptors, inducing the release of endocannabinoids via the PLCc/DGL pathway and retrogradely activating presynaptic CB1Rs. We also reported the involvement of AC/PKA in modulating vesicle endocytosis, which may account for the BDNF-induced calcium-dependent and -independent regulation of endocytosis. Thus, our study provides new insights into the BDNF/endocannabinoid-associated modulation of neurotransmission in physiological and pathologic processes.
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