TY - JOUR
T1 - M1 muscarinic acetylcholine receptors activate extracellular signal-regulated kinase in CA1 pyramidal neurons in mouse hippocampal slices
AU - Berkeley, Jennifer L.
AU - Gomeza, Jesus
AU - Wess, Jurgen
AU - Hamilton, Susan E.
AU - Nathanson, Neil M.
AU - Levey, Allan I.
N1 - Funding Information:
We thank members of the Levey lab for helpful discussions. We thank Dr. Masahisa Yamada for establishing the M3 receptor mutant mouse line used in this study. The generation of the M2 and M4 muscarinic receptor knockout mice was supported financially by Eli Lilly (Indianapolis, IN). This study was supported by: Alzheimer’s Association; a PhRMA Foundation Advanced Predoctoral Fellowship (J.L.B.); R01 NS26920 (N.M.N.); and R01 NS30454 (A.I.L.).
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
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U2 - 10.1006/mcne.2001.1042
DO - 10.1006/mcne.2001.1042
M3 - Article
C2 - 11922142
AN - SCOPUS:0035543554
SN - 1044-7431
VL - 18
SP - 512
EP - 524
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
IS - 5
ER -