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  • Title: The cannabinoid CB1 receptor mediates retrograde signals for depolarization-induced suppression of inhibition in cerebellar Purkinje cells.
    Author: Yoshida T, Hashimoto K, Zimmer A, Maejima T, Araishi K, Kano M.
    Journal: J Neurosci; 2002 Mar 01; 22(5):1690-7. PubMed ID: 11880498.
    Abstract:
    Action potential firing or depolarization of the postsynaptic neuron can induce a transient suppression of inhibitory synaptic inputs to the depolarized neuron in the cerebellum and hippocampus. This phenomenon, termed depolarization-induced suppression of inhibition (DSI), is initiated postsynaptically by an elevation of intracellular Ca2+ concentration ([Ca2+]i) and is expressed presynaptically as a suppression of the transmitter release. It is, therefore, thought that some retrograde signal must exist from the depolarized postsynaptic neurons to the presynaptic terminals. Recent studies on hippocampal neurons have revealed that endogenous cannabinoids (endocannabinoids) play a key role as a retrograde messenger. There are, however, conflicting reports that glutamate may be a candidate retrograde messenger for cerebellar DSI that acts on presynaptic group II metabotropic glutamate receptors (mGluRs). In this study, we examined whether endocannabinoids mediate retrograde signal for cerebellar DSI. We recorded IPSCs from Purkinje cells by stimulating putative basket cell axons in mouse cerebellar slices. DSI was readily induced in evoked IPSCs by a depolarizing pulse train. We found that DSI was completely occluded by a cannabinoid agonist, WIN55,212-2, was totally eliminated by a specific antagonist of the type 1 cannabinoid (CB1) receptor, SR141716A, and was deficient in the CB1 knock-out mouse. In contrast, a group II mGluR-specific agonist, (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine, did not completely occlude DSI, and an mGluR antagonist, (RS)-alpha-methyl-4-carboxyphenylglycine, had no depressant effect on DSI. These results clearly indicate that the CB1 receptor mediates retrograde signal for DSI in cerebellar Purkinje cells.
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