Presynaptic m1 muscarinic receptors are necessary for mGluR LTD in the hippocampus
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...
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2011
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| Online Access: | http://hdl.handle.net/1721.1/61403 https://orcid.org/0000-0003-2839-8228 |
| _version_ | 1826209964293619712 |
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| author | Kamsler, Ariel McHugh, Thomas J. Gerber, David Huang, Shu Ying Tonegawa, Susumu |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Kamsler, Ariel McHugh, Thomas J. Gerber, David Huang, Shu Ying Tonegawa, Susumu |
| author_sort | Kamsler, Ariel |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T14:37:31Z |
| format | Article |
| id | mit-1721.1/61403 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:37:31Z |
| publishDate | 2011 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/614032022-09-29T09:59:39Z Presynaptic m1 muscarinic receptors are necessary for mGluR LTD in the hippocampus Kamsler, Ariel McHugh, Thomas J. Gerber, David Huang, Shu Ying Tonegawa, Susumu Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Tonegawa, Susumu Kamsler, Ariel McHugh, Thomas J. Gerber, David Huang, Shu Ying Tonegawa, Susumu 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. 2011-03-04T14:49:53Z 2011-03-04T14:49:53Z 2008-04 2010-01 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/61403 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 https://orcid.org/0000-0003-2839-8228 en_US http://dx.doi.org/10.1073/pnas.0912540107 Proceedings of the National Academy of Sciences of the United States of America Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Kamsler, Ariel McHugh, Thomas J. Gerber, David Huang, Shu Ying Tonegawa, Susumu Presynaptic m1 muscarinic receptors are necessary for mGluR LTD in the hippocampus |
| title | Presynaptic m1 muscarinic receptors are necessary for mGluR LTD in the hippocampus |
| title_full | Presynaptic m1 muscarinic receptors are necessary for mGluR LTD in the hippocampus |
| title_fullStr | Presynaptic m1 muscarinic receptors are necessary for mGluR LTD in the hippocampus |
| title_full_unstemmed | Presynaptic m1 muscarinic receptors are necessary for mGluR LTD in the hippocampus |
| title_short | Presynaptic m1 muscarinic receptors are necessary for mGluR LTD in the hippocampus |
| title_sort | presynaptic m1 muscarinic receptors are necessary for mglur ltd in the hippocampus |
| url | http://hdl.handle.net/1721.1/61403 https://orcid.org/0000-0003-2839-8228 |
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