Endocannabinoid-Mediated Potentiation of Non-Nociceptive Synapses Contributes to Behavioral Sensitization

Endocannabinoids, such as 2-arachidonoyl glycerol (2-AG) and anandamide, can elicit long-term depression of both excitatory and inhibitory synapses. This latter effect will result in disinhibition and would therefore be expected to produce an increase in neural circuit output. However, there have been no examples directly linking endocannabinoid-mediated disinhibition to a change in a functional neurobehavioral circuit. The present study uses the well-characterized central nervous system (CNS) of the medicinal leech, Hirudo verbana, to examine the functional/behavioral relevance of endocannabinoid modulation of an identified afferent synapse. Bath-application of 2-AG potentiates synaptic transmission by pressure-sensitive sensory neurons (P cell) as well as the magnitude of the defensive shortening reflex elicited by P cell stimulation. This potentiation requires activation of TRPV-like channels. Endocannabinoid/TRPV signaling was found to produce sensitization of the shortening reflex elicited by either direct stimulation of nearby nociceptive afferents (N cells) or noxious stimulation applied to skin several segments away. In both cases heterosynaptic potentiation of P cell synapses were observed in parallel with an increase in the magnitude of the elicited shortening and both synaptic and behavioral effects were blocked by pharmacological inhibition of 2-AG synthesis or TRPV-like channel activation. Serotonin (5-HT) is known to play a critical role in sensitization in Hirudo and other animals and the 5-HT2 receptor antagonist, ritanserin, also blocked behavioral sensitization and the accompanying synaptic potentiation. These findings suggest a novel, endocannabinoid-mediated contribution to behavioral sensitization that may interact with known 5-HT-dependent modulatory processes.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2ztTyur