Berthoux, C. | Search bioRxiv

bioRxiv2021

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

The brain-derived neurotrophic factor (BDNF) and its effector Tropomyosin receptor kinase B (TrkB) mediate diverse forms of activity-dependent synaptic plasticity implicated in learning, neural circuit refinement, and brain diseases, including epilepsy and mood disorders. Here, we report that activity-dependent release of presynaptic BDNF elicits the release of postsynaptic BDNF in a TrkB- and calcium-dependent manner. This BDNF-induced BDNF release was required for the induction of presynaptic long-term potentiation (LTP) of excitatory transmission in the mouse dentate gyrus. Tonic and phasic activity of presynaptic type-1 cannabinoid receptors suppressed BDNF release and dampened LTP, while exposure to enriched environment elicited BDNF-mediated LTP. In addition to mediating presynaptic plasticity, BDNF-induced BDNF release could be an important mechanism in synaptic stabilization during the maturation and refinement of neuronal connections. One-Sentence SummaryThe brain-derived neurotrophic factor induces its own release to mediate long-lasting increase in neurotransmitter release.

neuroscience↗

bioRxiv2021

Retrograde adenosine/A2A receptor signaling mediates presynaptic hippocampal LTP and facilitates epileptic seizures

Retrograde signaling at the synapse is a fundamental way by which neurons communicate and neuronal circuit function is fine-tuned upon activity. While long-term changes in neurotransmitter release commonly rely on retrograde signaling, the mechanisms remain poorly understood. Here, we identified adenosine/A2A receptor (A2AR) as a novel retrograde signaling pathway underlying presynaptic long-term potentiation (LTP) at a hippocampal excitatory circuit critically involved in memory and epilepsy. Transient burst activity of a single dentate granule cell induced LTP of mossy cell synaptic inputs, a BDNF/TrkB-dependent form of plasticity that facilitates seizures. Postsynaptic TrkB activation released adenosine from granule cells, uncovering a non-conventional BDNF/TrkB signaling mechanism. Moreover, presynaptic A2ARs were necessary and sufficient for LTP. Lastly, seizure induction released adenosine in a TrkB-dependent manner, while removing A2ARs or TrkB from the dentate gyrus had anti-convulsant effects. By mediating presynaptic LTP, adenosine/A2AR retrograde signaling may modulate dentate gyrus-dependent learning and promote epileptic activity. HighlightsO_LIPostsynaptic firing induces presynaptic LTP at mossy cell to granule cell synapses C_LIO_LIPostsynaptic TrkB activation induces adenosine release from granule cells C_LIO_LIPresynaptic adenosine A2A receptors are necessary and sufficient to induce LTP C_LIO_LIAdenosine/A2AR signaling within the dentate gyrus is pro-convulsant C_LI In BriefNasrallah et al. report a novel retrograde signaling pathway at hippocampal synapses that involves postsynaptic TrkB-dependent release of adenosine and the activation of presynaptic A2A receptors. This pathway mediates presynaptic long-term potentiation at a key hippocampal excitatory synapse and can also promote epileptic seizures.

neuroscience↗