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Presynaptic m1 Muscarinic Receptors Are Necessary for mGluR Long-Term Depression in the Hippocampus

Presynaptic m1 Muscarinic Receptors Are Necessary for mGluR Long-Term Depression in the Hippocampus

Ariel Kamsler, Thomas J McHugh, David Gerber, Shu Ying Huang, Susumu Tonegawa

Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1618-23.

PMID: 20080609

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
ALP162870293	(S)-3,5-Dihydroxyphenylglycine hydrate		162870-29-3 (anhydrous)	Price

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