M1 muscarinic receptor facilitates cognitive function by interplay with AMPA receptor GluA1 subunit.

Lan-Xue Zhao, Yan-Hui Ge, Cai-Hong Xiong, Ling Tang, Ying-Hui Yan, Ping-Yee Law, Yu Qiu, Hong-Zhuan Chen
Author Information
  1. Lan-Xue Zhao: Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  2. Yan-Hui Ge: Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  3. Cai-Hong Xiong: Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  4. Ling Tang: Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  5. Ying-Hui Yan: Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  6. Ping-Yee Law: Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA.
  7. Yu Qiu: Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  8. Hong-Zhuan Chen: Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

M1 muscarinic acetylcholine receptors (M1 mAChRs) are the most abundant muscarinic receptors in the hippocampus and have been shown to have procognitive effects. AMPA receptors (AMPARs), an important subtype of ionotropic glutamate receptors, are key components in neurocognitive networks. However, the role of AMPARs in procognitive effects of M1 mAChRs and how M1 mAChRs affect the function of AMPARs remain poorly understood. Here, we found that basal expression of GluA1, a subunit of AMPARs, and its phosphorylation at Ser845 were maintained by M1 mAChR activity. Activation of M1 mAChRs promoted membrane insertion of GluA1, especially to postsynaptic densities. Impairment of hippocampus-dependent learning and memory by antagonism of M1 mAChRs paralleled the reduction of GluA1 expression, and improvement of learning and memory by activation of M1 mAChRs was accompanied by the synaptic insertion of GluA1 and its increased phosphorylation at Ser845. Furthermore, abrogation of phosphorylation of Ser845 residue of GluA1 ablated M1 mAChR-mediated improvement of learning and memory. Taken together, these results show a functional correlation of M1 mAChRs and GluA1 and the essential role of GluA1 in M1 mAChR-mediated cognitive improvement.-Zhao, L.-X., Ge, Y.-H., Xiong, C.-H., Tang, L., Yan, Y.-H., Law, P.-Y., Qiu, Y., Chen, H.-Z. M1 muscarinic receptor facilitates cognitive function by interplay with AMPA receptor GluA1 subunit.

Keywords

MeSH Term

Animals
Chromosome Pairing
Cognition
Hippocampus
Learning
Male
Memory
Mice
Mice, Inbred C57BL
Mice, Transgenic
Phosphorylation
Protein Subunits
Receptor, Muscarinic M1
Receptors, AMPA
Receptors, Muscarinic

Chemicals

Protein Subunits
Receptor, Muscarinic M1
Receptors, AMPA
Receptors, Muscarinic

Word Cloud

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