Remembering Mechanosensitivity of NMDA Receptors
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Description
An increase in post-synaptic Ca2+ conductance through activation of the ionotropic N-methyl-D-aspartate receptor (NMDAR) and concomitant structural changes are essential for the initiation of long-term potentiation (LTP) and memory formation. Memories can be initiated by coincident events, as occurs in classical conditioning, where the NMDAR can act as a molecular coincidence detector. Binding of glutamate and glycine, together with depolarization of the postsynaptic cell membrane to remove the Mg2+ channel pore block, results in NMDAR opening for Ca2+ conductance. Accumulating evidence has implicated both force-from-lipids and protein tethering mechanisms for mechanosensory transduction in NMDAR, which has been demonstrated by both, membrane stretch and application of amphipathic molecules such as arachidonic acid (AA). The contribution of mechanosensitivity to memory formation and consolidation may be to increase activity of the NMDAR leading to facilitated memory formation. In this review we look back at the progress made toward understanding the physiological and pathological role of NMDA receptor channels in mechanobiology of the nervous system and consider these findings in like of their potential functional implications for memory formation. We examine recent studies identifying mechanisms of both NMDAR and other mechanosensitive channels and discuss functional implications including gain control of NMDA opening probability. Mechanobiology is a rapidly growing area of biology with many important implications for understanding form, function and pathology in the nervous system.
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ID Code: | 232733 |
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Item Type: | Contribution to Journal (Review article) |
Refereed: | Yes |
Additional Information: | Funding Information: This work was supported by a grant APP1135076 and a Principal Research Fellowship APP1135974 to BM from the National Health and Medical Research Council (NHMRC) of Australia, and research support from the University of Tasmania School of Medicine to LJ. |
Measurements or Duration: | 11 pages |
Keywords: | amygdala, force, learning, lipids, mechanobiology, memory, NMDA |
DOI: | 10.3389/fncel.2019.00533 |
ISSN: | 1662-5102 |
Pure ID: | 111721093 |
Divisions: | Past > Institutes > Institute of Health and Biomedical Innovation |
Funding Information: | This work was supported by a grant APP1135076 and a Principal Research Fellowship APP1135974 to BM from the National Health and Medical Research Council (NHMRC) of Australia, and research support from the University of Tasmania School of Medicine to LJ. We thank Dr. Yury A. Nikolaev for designing Figure 1 as well as for his comments and proofreading the manuscript. AB would like to acknowledge the UA-DAAD Australia-Germany Joint Research Co-operation Scheme for funding. |
Copyright Owner: | 2019 The Authors |
Copyright Statement: | This work is covered by copyright. Unless the document is being made available under a Creative Commons Licence, you must assume that re-use is limited to personal use and that permission from the copyright owner must be obtained for all other uses. If the document is available under a Creative Commons License (or other specified license) then refer to the Licence for details of permitted re-use. It is a condition of access that users recognise and abide by the legal requirements associated with these rights. If you believe that this work infringes copyright please provide details by email to qut.copyright@qut.edu.au |
Deposited On: | 22 Jun 2022 01:58 |
Last Modified: | 16 Jul 2024 16:38 |
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