Canna~Fangled Abstracts

BDNF-endocannabinoid interactions at neocortical inhibitory synapses require phospholipase C signaling.

By December 18, 2013No Comments
J Neurophysiol. 2013 Dec 11. [Epub ahead of print]

pm8BDNF-endocannabinoid interactions at neocortical inhibitory synapses require phospholipase C signaling.

Abstract

Endogenous cannabinoids (endocannabinoids) and neurotrophins, particularly brain-derived neurotrophic factor (BDNF), are potent synaptic modulators that are expressed throughout the forebrain and play critical roles in many behavioral processes. Although the effects of BDNF at excitatory synapses have been well characterized, the mechanisms of action of BDNF at inhibitory synapses are not well understood. Previously we have found that BDNF suppresses presynaptic GABA release in layer 2/3 of the neocortex via postsynaptic trkB receptor-induced release of endocannabinoids. To examine the intracellular signaling pathways that underlie this effect, we used pharmacological approaches and whole-cell patch clamp techniques in layer 2/3 pyramidal neurons of somatosensory cortex in brain slices from juvenile Swiss CD1 mice. Our results indicated that phospholipase Cγ (PLCγ) is involved in the CB1R-mediated synaptic effect of BDNF, as the BDNF effect was blocked in the presence of the broad-spectrum PLC inhibitors U-73122 and edelfosine, while the inactive analog U-73343 did not alter the suppressive effect of BDNF at inhibitory synapses. Endocannabinoid release can also be triggered by metabotropic glutamate receptor (mGluR)-mediated activation of PLCβ, and BDNF has been shown to enhance spontaneous glutamate release. An mGluR antagonist, E4CPG, however, did not block the BDNF effect. In addition, the effect of BDNF was independent of other signaling pathways downstream of trkB receptor activation, namely mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways, as well as protein kinase C signaling.

KEYWORDS:

BDNF, cannabinoid, cerebral cortex, phospholipase C

PMID:

 

24335212

 

[PubMed – as supplied by publisher]
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