title: Presynaptic m1 muscarinic receptors are necessary for mGluR long-term depression in the hippocampus.
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.
authors.affiliation: RIKEN-MIT Neuroscience Research Center, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Ariel
authors.initials: A
authors.lastname: Kamsler
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: McHugh
authors.forename: David
authors.initials: D
authors.lastname: Gerber
authors.forename: Shu Ying
authors.initials: SY
authors.lastname: Huang
authors.forename: Susumu
authors.initials: S
authors.lastname: Tonegawa
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000378:metabolism*; D036881:Long-Term Synaptic Depression; D051379:Mice; D018345:Mice, Knockout; D011493:Protein Kinase C / Q000378:metabolism; D043643:Receptor, Muscarinic M1 / Q000172:deficiency / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
chemical_list: D043643:Receptor, Muscarinic M1; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D011493:Protein Kinase C