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Long‐term depression of presynaptic cannabinoid receptor function at parallel fibre synapses
Author(s) -
Yang Ying,
KrekoPierce Tabita,
Howell Rebecca,
Pugh Jason R.
Publication year - 2019
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp277727
Subject(s) - cannabinoid receptor , neuroscience , endocannabinoid system , long term depression , synaptic plasticity , synapse , parallel fiber , stimulation , chemistry , depolarization induced suppression of inhibition , cerebellum , purkinje cell , receptor , biology , agonist , glutamate receptor , biochemistry , ampa receptor
Key points 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.Abstract Cannabinoid type‐1 receptors (Cb1R) are expressed in the presynaptic membrane of many synapses, including parallel fibre‐Purkinje cell synapses in the cerebellum, where they are involved in short‐ and long‐term plasticity of synaptic responses. We show that Cb1R expression itself is a plastic property of the synapse regulated by physiological activity patterns. We made patch clamp recordings from Purkinje cells in cerebellar slices and assessed Cb1R activity by measuring depolarization‐induced suppression of excitation (DSE). We find that DSE is normally stable at parallel fibre synapses but, following 4 Hz stimulation, DSE is persistently reduced and recovers more rapidly. Using a combination of electrophysiology, pharmacology and biochemistry, we show that changes in DSE are a result of the reduced expression of Cb1Rs and increased degradation of endocannabinoids by monoacylglycerol lipase. Long‐term changes in presynaptic Cb1R expression may alter other forms of Cb1R‐dependent plasticity at parallel fibre synapses, priming or inhibiting the circuit for associative learning.