Muscarinic acetylcholine receptor-dependent and NMDA receptor-dependent LTP and LTD share the common AMPAR trafficking pathway

iScience. 2023 Feb 3;26(3):106133. doi: 10.1016/j.isci.2023.106133.

Tomonari Sumi ¹ ², Kouji Harada ³ ⁴

Affiliations

1 Research Institute for Interdisciplinary Science, Okayama University, 3-1-1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
2 Department of Chemistry, Faculty of Science, Okayama University, 3-1-1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
3 Department of Computer Science and Engineering, Toyohashi University of Technology, Tempaku-cho, Toyohashi 441-8580, Japan.
4 Center for IT-Based Education, Toyohashi University of Technology, Tempaku-cho, Toyohashi, 441-8580, Japan.

PMID: 36866246 DOI: 10.1016/j.isci.2023.106133

Abstract

The forebrain cholinergic system promotes higher brain function in part by signaling through the M₁ Muscarinic Acetylcholine Receptor (mAChR). Long-term potentiation (LTP) and long-term depression (LTD) of excitatory synaptic transmission in the hippocampus are also induced by mAChR. An AMPA Receptor (AMPAR) trafficking model for hippocampal neurons has been proposed to simulate N-methyl-D-aspartate receptor (NMDAR)-dependent synaptic plasticity in the early phase. In this study, we demonstrated the validity of the hypothesis that the mAChR-dependent LTP/LTD shares a common AMPAR trafficking pathway associated with NMDAR-dependent LTP/LTD. However, unlike NMDAR, CA²⁺ influx into the spine cytosol occurs owing to the CA²⁺ stored inside the ER and is induced via the activation of inositol 1,4,5-trisphosphate (IP3) receptors during M1 mAChR activation. Moreover, the AMPAR trafficking model implies that alterations in LTP and LTD observed in Alzheimer's disease could be attributed to age-dependent reductions in AMPAR expression levels.

Keywords

Cellular neuroscience; Cellular physiology; Molecular neuroscience.

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