M1 muscarinic acetylcholine receptors activate extracellular signal-regulated kinase in CA1 pyramidal neurons in mouse hippocampal slices

Jennifer L. Berkeley, Jesus Gomeza, Jurgen Wess, Susan E. Hamilton, Neil M. Nathanson, Allan I. Levey

Research output: Contribution to journalArticlepeer-review

Abstract

Activation of extracellular signal-regulated kinases (ERK) is crucial for many neural functions, including learning, memory, and synaptic plasticity. As muscarinic acetylcholine receptors (mAChR) modulate many of the same higher brain functions as ERK, we examined mAChR-mediated ERK activation in mouse hippocampal slices. The cholinergic agonist carbachol caused an atropine-sensitive ERK activation in the dendrites and somata CA1 pyramidal neurons. To determine the responsible mAChR subtype, we combined pharmacologic and genetic approaches. Pretreatment with M1 antagonists inhibited ERK activation. Furthermore, mAChR-induced ERK activation was absent in slices from M1 knockout mice. ERK activation was normal in slices derived from other mAChR subtype knockouts (M2, M3, and M4), although these other subtypes are expressed in many of the same neurons. Thus, we demonstrate divergent functions for the different mAChR subtypes. We conclude that M1 is responsible for mAChR-mediated ERK activation, providing a mechanism by which M1 may modulate learning and memory.

Original languageEnglish (US)
Pages (from-to)512-524
Number of pages13
JournalMolecular and Cellular Neuroscience
Volume18
Issue number5
DOIs
StatePublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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