Long‐term Depression of Presynaptic Cannabinoid Receptor Function at Parallel Fibre Synapses

Inhibition of synaptic responses by activation of presynaptic cannabinoid type‐1 (Cb1) receptors is reduced at parallel fibre synapses in the cerebellum following 4 Hz stimulation. Activation of adenylyl cyclase is necessary and sufficient for down‐regulation of Cb1 receptors induced by 4 Hz stimulation. 4 Hz stimulation reduces Cb1 receptor function by (i) increasing the rate of endocannabinoid clearance from the synapse and (ii) decreasing expression of Cb1 receptors.