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Synapse. 2018 Oct 17:e22075. doi: 10.1002/syn.22075. [Epub ahead of print]

Endogenous cannabinoids mediate the effect of BDNF at CA1 inhibitory synapses in the hippocampus.

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Department of Neuroscience, University of Connecticut School of Medicine, Farmington, Connecticut.


Brain-derived neurotrophic factor (BDNF), traditionally known for promoting neuronal growth and development, is also a modulator of synaptic transmission. In addition to the well-characterized effects at excitatory synapses, BDNF has been shown to acutely suppress inhibitory neurotransmission; however, the underlying mechanisms are unclear. We have previously shown that at inhibitory synapses in layer 2/3 of the somatosensory cortex, BDNF induces the mobilization of endogenous cannabinoids (eCBs) that act retrogradely to suppress GABA release. Here, we hypothesized that in the hippocampus, BDNF acts similarly via eCB signaling to suppress GABAergic transmission. We found that the acute application of BDNF reduced the spontaneous inhibitory postsynaptic currents (sIPSCs) via postsynaptic TrkB receptor activation. The suppressive effects of BDNF required eCB signaling, as this effect on sIPSCs was prevented by a CB1 receptor antagonist. Further, blocking the postsynaptic eCB release prevented the effect of BDNF, whereas eCB reuptake inhibition enhanced the effect of BDNF. These results suggest that BDNF triggers the postsynaptic release of eCBs. To identify the specific eCB release by BDNF, we tested the effects of disrupting the synthesis or degradation of 2-arachidonoylcglycerol (2-AG). Blocking 2-AG synthesis prevented the effect of BDNF and blocking 2-AG degradation enhanced the effect of BDNF. However, there was no change in the effect of BDNF when anandamide degradation was blocked. Collectively, these results suggest that in the hippocampus, BDNF-TrkB signaling induces the postsynaptic release of the endogenous cannabinoid 2-AG, which acts retrogradely on the presynaptic CB1 receptors to suppress GABA release.


BDNF; CB1; TrkB; endocannabinoid; synaptic transmission


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