Short-Term Retrograde Inhibition of GABAergic Synaptic Currents in Rat Purkinje Cells Is Mediated by Endogenous Cannabinoids
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Discussion
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Implication
Laboratory study demonstrates that retrograde endocannabinoid signaling suppresses GABAergic transmission in rat Purkinje cells, indicating presynaptic CB1 receptors control synaptic plasticity.
Key Points
- To determine whether endogenous cannabinoids act as retrograde messengers mediating depolarization-induced suppression of inhibition at GABAergic synapses onto cerebellar Purkinje cells.
- Conducted paired electrophysiological recordings of evoked and miniature inhibitory postsynaptic currents (eIPSCs and mIPSCs) in rat cerebellar parasagittal slices.
- Treated slices with the CB1 receptor antagonist AM-251 (500 nM) or the CB1 receptor agonist WIN 55-212,2 (5 µM).
- Recorded action potential-evoked calcium transients in presynaptic varicosities under pharmacological CB1 receptor stimulation.
- Application of CB1 antagonist AM-251 abolished depolarization-induced suppression of inhibition for evoked IPSCs and markedly reduced suppression of miniature IPSCs.
- CB1 agonist WIN 55-212,2 mimicked and occluded depolarization-induced suppression of inhibition while decreasing action potential-evoked presynaptic calcium rises.
Cite This Study
Diana et al. (2002) studied this question.