Role for Endogenous BDNF in Endocannabinoid-Mediated Long-Term Depression at Neocortical Inhibitory Synapses
نویسندگان
چکیده
The endogenous cannabinoid (endocannabinoid) system is an important regulator of synaptic function. Endocannabinoids acutely modulate inhibitory and excitatory transmission, and also mediate long-term depression at GABAergic and glutamatergic synapses. Typically, endocannabinoid synthesis and release is stimulated by depolarization-induced calcium influx and/or activation of phospholipase-C (PLC) signaling triggered by mGluR activation. Recently it has been shown that brain-derived neurotrophic factor (BDNF) can also induce endocannabinoid release. Although there is growing evidence for cross-talk between BDNF and endocannabinoid signaling, little is known about the functional relevance of these interactions. In the present studies, we examined BDNF - endocannabinoid interactions in regulating activity-dependent long-term depression at inhibitory synapses (iLTD). We found that theta burst stimulation (TBS) in layer 2/3 of mouse somatosensory cortical slices can induce a form of endocannabinoid-mediated iLTD that is independent of metabotropic glutamate receptor (mGluR) activation. This endocannabinoid-dependent iLTD, however, requires endogenous BDNF-trkB signaling, as it is blocked by a trk tyrosine kinase inhibitor and by a trkB receptor antagonist, and also requires activation of diacylglycerol lipase (DAG-lipase, DGL). In addition, endocannabinoid-mediated iLTD can be induced by combining a subthreshold concentration of exogenous BDNF with weak TBS stimulation that by itself is insufficient to induce iLTD. Taken together, our results suggest that TBS can induce the release of endogenous BDNF, which triggers DGL-dependent endocannabinoid mobilization and cannabinoid receptor-dependent iLTD at layer 2/3 cortical synapses.
منابع مشابه
Role for Endogenous BDNF in Endocannabinoid-mediated Long-Term Depression at Neocortical Inhibitory Synapses BDNF regulates endocannabinoid-mediated plasticity
process. This article is distributed under the terms of the Creative Commons Attribution License (http:// creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. Copyright © 2015 Society for Neuroscience Research Article: New Research | Neuronal Excitability Role for Endogenous BDNF...
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ورودعنوان ژورنال:
- eNeuro
دوره 2 2 شماره
صفحات -
تاریخ انتشار 2015