M-1 muscarinic acetylcholine receptors activate extracellular signal-regulated kinase in CA1 pyramidal neurons in mouse hippocampal slices

Activation of extracellular signal-regulated kinases (ERK) Is crucial for m any neural functions, including learning, memory, and synaptic plasticity. As muscarinic acetylcholine receptors (mAChR) modulate many of the same hig her brain functions as ERK, we examined mAChR-mediated ERK activation in mo use hippocampal slices. The cholinergic agonist carbachol caused an atropin e-sensitive ERK activation in the dendrites and somata CAI pyramidal neuron s. To determine the responsible mAChR subtype, we combined pharmacologic an d genetic approaches. Pretreatment with M-1 antagonists inhibited ERK activ ation. Furthermore, mAChR-induced ERK activation was absent in slices from M-1 knockout mice. ERK activation was normal in slices derived from other m AChR subtype knockouts (M-2, M-3, and M-4), although these other subtypes a re expressed in many of the same neurons. Thus, we demonstrate divergent fu nctions for the different mAChR subtypes. We conclude that M-1 is responsib le for mAChR-mediated ERK activation, providing a mechanism by which M-1 ma y modulate learning and memory.