Presynaptic m1 muscarinic receptors are necessary for mGluR LTD in the hippocampus
Name
Kamsler-2010-Presynaptic m1 musca.pdf
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Author(s)
Kamsler, Ariel
McHugh, Thomas J.
Gerber, David
Huang, Shu Ying
Tonegawa, Susumu
Date Issued
April 2008
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
National Academy of Sciences (U.S.)
Citation
Kamsler, Ariel et al. “Presynaptic m1 muscarinic receptors are necessary for mGluR long-term depression in the hippocampus.” Proceedings of the National Academy of Sciences 107.4 (2010): 1618 -1623. Copyright ©2010 by the National Academy of Sciences
Version
Final published version
Abstract
To investigate the role of M1 muscarininc acetylcholine receptors (m1 receptors) in metabotropic glutamate receptor (mGluR)-mediated long-term depression (LTD), we produced mouse lines in which deletion of the m1 gene is restricted to the forebrain (FB–m1KO) or hippocampal CA3 pyramidal neurons (CA3–m1KO). Stimulation in FB–m1KO hippocampal slices resulted in excitatory postsynaptic potentials and long-term synaptic plasticity (long-term potentiation and LTD) similar to controls. The mice were deficient in (S)-3,5-dihydroxyphenylglycine hydrate (DHPG)-induced mGluR LTD, which correlated with a presynaptic increase in the release of neurotransmitters. Protein kinase C (PKC) activity, which is downstream from both mGluRs and m1 receptors, was reduced in CA3 but not in CA1. The presynaptic requirement of m1 receptors was confirmed by the lack of DHPG-induced mGluR LTD in the CA1 of slices from CA3–m1KO mice. mGluR LTD was rescued by stimulating PKC activity pharmacologically in CA3–m1KO mice. These data confirm a role for PKC activation in presynaptic induction of mGluR LTD and distinguish between the roles of mGluRs and m1 receptors.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
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DOI of Published Version
https://doi.org/10.1073/pnas.0912540107
