Properties of cannabinoid-dependent long-term depression in the leech

Previously, a cannabinoid-dependent form of long-term depression (LTD) was discovered at the polysynaptic connection between the touch mechanosensory neuron and the S interneuron (Li and Burrell in J Comp Physiol A 195:831-841, 2009). In the present study, the physiological properties of this cannabinoid-dependent LTD were examined. Increases in intracellular calcium in the S interneuron are necessary for this form of LTD in this circuit. Calcium signals contributing to cannabinoid-dependent LTD are mediated by voltage-dependent calcium channel and release of calcium from intracellular stores. Inositol triphosphate receptors, but not ryanodine receptors, appear to mediate this store-released calcium signal. Cannabinoid-dependent LTD also requires activation of metabotropic serotonin receptors, possibly a serotonin type 2-like receptor. Finally, this form of LTD involves the stimulation of nitric oxide synthase and a decrease in cyclic adenosine monophosphate signaling, both of which appeared to be downstream of cannabinoid receptor activation. Based on these findings, the cellular signaling mechanisms of cannabinoid-dependent LTD in the leech are remarkably similar to vertebrate forms of cannabinoid-dependent synaptic plasticity.