Muscarinic cannabinoid suppression of excitation, a novel form of coincidence detection.
Pharmacological research February 1, 2025 Michaela Dvorakova, Ken Mackie, Alex Straiker 2 citations
Coactivating muscarinic acetylcholine receptors and eliciting depolarization-induced suppression of excitation (DSE) in autaptic hippocampal neurons produces a roughly 40% inhibition of excitatory transmission lasting about 10 minutes. This inhibition, termed muscarinic cannabinoid suppression of excitation (MCSE), requires CB1 and muscarinic M3/M5 receptors and is absent in CB1 receptor knockout neurons. Once established, it is reversed by a CB1 antagonist but not a muscarinic antagonist, indicating persistent CB1 receptor activation. MCSE can be mimicked by coapplying muscarinic and cannabinoid agonists and depends on calcium release from internal stores. This represents a novel coincidence detection between cannabinoid and muscarinic signaling systems, potentially modulating hippocampal signaling with implications for learning, memory, epilepsy, and addiction.