Remembering Mechanosensitivity of NMDA Receptors

Luke R Johnson; Andrew R Battle; Boris Martinac

doi:10.3389/fncel.2019.00533

Remembering Mechanosensitivity of NMDA Receptors

Front Cell Neurosci. 2019 Dec 5:13:533. doi: 10.3389/fncel.2019.00533. eCollection 2019.

Authors

Luke R Johnson^{1

2

3

4

5}, Andrew R Battle^{5

6

7}, Boris Martinac^{1

2}

Affiliations

¹ Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia.
² St. Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW, Australia.
³ Division of Psychology, School of Medicine, University of Tasmania, Launceston, TAS, Australia.
⁴ Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
⁵ School of Biomedical Sciences, Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, QLD, Australia.
⁶ Prince Charles Hospital Northside Clinical Unit, School of Clinical Medicine, The University of Queensland, Brisbane, QLD, Australia.
⁷ Translational Research Institute, Woolloongabba, QLD, Australia.

Abstract

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.

Keywords: NMDA; amygdala; force; learning; lipids; mechanobiology; memory.

Publication types

Review