دورية أكاديمية
Activation of Muscarinic M1 Acetylcholine Receptors Induces Long-Term Potentiation in the Hippocampus.
العنوان: | Activation of Muscarinic M1 Acetylcholine Receptors Induces Long-Term Potentiation in the Hippocampus. |
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المؤلفون: | Dennis SH; Neuroscience, Eli Lilly & Company, Windlesham, Surrey GU20 6PH, UK., Pasqui F; Neuroscience, Eli Lilly & Company, Windlesham, Surrey GU20 6PH, UK., Colvin EM; Neuroscience, Eli Lilly & Company, Windlesham, Surrey GU20 6PH, UK., Sanger H; Neuroscience, Eli Lilly & Company, Windlesham, Surrey GU20 6PH, UK., Mogg AJ; Neuroscience, Eli Lilly & Company, Windlesham, Surrey GU20 6PH, UK., Felder CC; Neuroscience, Eli Lilly & Company, Indianapolis, IN 46285, USA., Broad LM; Neuroscience, Eli Lilly & Company, Windlesham, Surrey GU20 6PH, UK., Fitzjohn SM; Neuroscience, Eli Lilly & Company, Windlesham, Surrey GU20 6PH, UK School of Physiology and Pharmacology, University of Bristol, Bristol BS8 1TD, UK., Isaac JT; Neuroscience, Eli Lilly & Company, Windlesham, Surrey GU20 6PH, UK., Mellor JR; School of Physiology and Pharmacology, University of Bristol, Bristol BS8 1TD, UK. |
المصدر: | Cerebral cortex (New York, N.Y. : 1991) [Cereb Cortex] 2016 Jan; Vol. 26 (1), pp. 414-26. Date of Electronic Publication: 2015 Oct 15. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 9110718 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-2199 (Electronic) Linking ISSN: 10473211 NLM ISO Abbreviation: Cereb Cortex Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: New York, NY : Oxford University Press, c1991- |
مواضيع طبية MeSH: | Cholinergic Agents/*pharmacology , Hippocampus/*metabolism , Long-Term Potentiation/*drug effects , Neuronal Plasticity/*drug effects , Receptor, Muscarinic M1/*metabolism , Synapses/*drug effects, Animals ; Excitatory Postsynaptic Potentials/drug effects ; Excitatory Postsynaptic Potentials/physiology ; Long-Term Potentiation/physiology ; Mice, Knockout ; Neuronal Plasticity/physiology ; Pyramidal Cells/cytology ; Pyramidal Cells/drug effects ; Synapses/physiology ; Synaptic Transmission/physiology |
مستخلص: | Muscarinic M1 acetylcholine receptors (M1Rs) are highly expressed in the hippocampus, and their inhibition or ablation disrupts the encoding of spatial memory. It has been hypothesized that the principal mechanism by which M1Rs influence spatial memory is by the regulation of hippocampal synaptic plasticity. Here, we use a combination of recently developed, well characterized, selective M1R agonists and M1R knock-out mice to define the roles of M1Rs in the regulation of hippocampal neuronal and synaptic function. We confirm that M1R activation increases input resistance and depolarizes hippocampal CA1 pyramidal neurons and show that this profoundly increases excitatory postsynaptic potential-spike coupling. Consistent with a critical role for M1Rs in synaptic plasticity, we now show that M1R activation produces a robust potentiation of glutamatergic synaptic transmission onto CA1 pyramidal neurons that has all the hallmarks of long-term potentiation (LTP): The potentiation requires NMDA receptor activity and bi-directionally occludes with synaptically induced LTP. Thus, we describe synergistic mechanisms by which acetylcholine acting through M1Rs excites CA1 pyramidal neurons and induces LTP, to profoundly increase activation of CA1 pyramidal neurons. These features are predicted to make a major contribution to the pro-cognitive effects of cholinergic transmission in rodents and humans. (© The Author 2015. Published by Oxford University Press.) |
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معلومات مُعتمدة: | 101029 United Kingdom Wellcome Trust; United Kingdom Biotechnology and Biological Sciences Research Council |
فهرسة مساهمة: | Keywords: CA1; hippocampus; long-term potentiation; muscarinic m1 receptor; synaptic plasticity |
المشرفين على المادة: | 0 (Cholinergic Agents) 0 (Receptor, Muscarinic M1) |
تواريخ الأحداث: | Date Created: 20151017 Date Completed: 20160929 Latest Revision: 20191008 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC4677984 |
DOI: | 10.1093/cercor/bhv227 |
PMID: | 26472558 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1460-2199 |
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DOI: | 10.1093/cercor/bhv227 |