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Journal of Integrative Neuroscience  2019, Vol. 18 Issue (2): 181-185    DOI: 10.31083/j.jin.2019.02.6101
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The tripartite mechanism as the basis for a biochemical memory engram
Gerard Marx1, Chaim Gilon2, *()
1 MX Biotech Ltd., Jerusalem 95744, Israel
2 Institute of Chemistry, Hebrew University, Jerusalem 91904, Israel
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Abstract  

In this paper, we address the enigma of the memory engram, the physical trace of memory in terms of its composition, processes, and location. A neurochemical approach assumes that neural processes hinge on the same terms used to describe the biochemical functioning of other biological tissues and organs. We define a biochemical process, a tripartite mechanism involving the interactions of neurons with their neural extracellular matrix, trace metals, and neurotransmitters as the basis of a biochemical memory engram. The latter inextricably link physiological responses, including sensations with affective states, such as emotions.

Key words:  Cognitive information      affective biochemistry      trace metals      neurotransmitters      extracellular matrix      memory engram      emotive memory     
Submitted:  11 January 2019      Accepted:  10 June 2019      Published:  30 June 2019     
*Corresponding Author(s):  Chaim Gilon     E-mail:  gilon@vms.huji.ac.il

Cite this article: 

Gerard Marx, Chaim Gilon. The tripartite mechanism as the basis for a biochemical memory engram. Journal of Integrative Neuroscience, 2019, 18(2): 181-185.

URL: 

https://jin.imrpress.com/EN/10.31083/j.jin.2019.02.6101     OR     https://jin.imrpress.com/EN/Y2019/V18/I2/181

Table 1  Kinetics of various neural processes.
Process Time scale
Protein chain synthesis 10-1 sec per amino acid
RNA elongation 10-2 sec per base
DNA elongation 10-3 sec per base
Neural firing rate 10-2 sec
Neuro-electric impulse 1-100 m/sec
Neural GPCR receptor diffusion 10-1 to 10-3 μm2 sec-1
Ca+2 diffusion in nECM 2.3 × 10-6 cm2/s
Molecular binding events 10-7 sec
Protein turnover (replacement) 3 months
Mosaic diffusion over neural surface 10-1 to 10-3 μm2/sec
Ionic memory chip byte encoding 10-7 sec
Figure 1.  Chemo-graphic representations of the reaction of an nECM binding site for a metal cation, an "address". The binding of a NTs to the metal-centered cuinfo confers an emotive context (Adapted from Marx and Gilon, 2016).

Figure 2.  The neuron is surrounded by nECM(GAG lattice not shown) which serves as a neurochemical "library" wherein units of encoded memories are stored as cuinfo. The colored boxes representing the individual cuinfo described in Figure1, arenottoscale, astheyareof molecular dimension (i.e. 10 nm) compared to the 10-100 μm scale of the neuron and its parts. The different colors indicate complexes with different combinations of NTs and metal cations.

[1] Agnati, L. F., Ferré, S., Leo, G., Lluis, C., Canela, E., Franco, R. and Fuxe, K. (2004) On the molecular basis of the receptor mosaic hypothesis of the engram. Cellular and Molecular Neurobiology, 24, 501-16.
[2] Amtul, Z. and Rahman, A. (2016) Neural plasticity and memory: Is memory encoded in hydrogen bonding patterns? The Neuroscientist 22, 9-18.
[3] Arellano, J. I., Espinosa, A., Fairen, A., Yuste, R. and DeFelipe, J. (2007) Non-synaptic dendritic spines in neocortex. Neuroscience 145, 464-469.
[4] Arshavsky,, Y.I. (2006) The seven sins of the Hebbian synapse: can the hypothesis of synaptic plasticity explain long-term memory consolidation? Progress in Neurobiology 80, 99-113.
[5] Becker, J.S., Zoriy, M.V., Pickhardt, C., Palomero-Gallagher, N. and Zilles, K. (2005) Imaging of copper, zinc, and other elements in thin sections of human brain samples (hippocampus) by laser ablation inductively coupled plasma mass spectrometry. Analytical Chemistry 77, 3208-3216.
[6] Becker,, J.S. (2010) Bioimaging of metals in brain tissue from micrometre to nanometre scale by laser ablation inductively coupled plasma mass spectrometry: State of the art and perspectives. International Journal Mass Spectrometry 289, 65-75.
[7] Bogoch,, S. (1968) The Biochemistry of Memory: With an Inquiry into the Function of Brain Mucoids. Oxford University Press, London.
[8] Brady,, S., Albers, W. R. and Price,, D. (2011) Basic Neurochemistry. Principles of Molecular, Cellular, and Medical Neurobiology 8 th ed., Elsevier Science , New York.
[9] Budnik, V., Ruiz-Cañada, C., and Wendler, F. (2016) Extracellular vesicles round off communication in the nervous system. Nature 17, 160-172.
[10] Cacha, L. A., Ali, J., Rizvi, Z. H., Yupapin, P. P. and Poznanski, R. R. (2017) Nonsynaptic plasticity model of long-term memory engrams. Journal of Integrative Neuroscience 16, 493-509.
[11] Corringer, J., Poitevin, F., Prevost, M., Sauguet, L., Delarue, M. and Changeux, J. P. (2012) Structure and pharmacology of pentameric receptor channels: From bacteria to brain. Structure 20, 941-956.
[12] Cserr,, H. ( Ed). (1986) The Neuronal Environment. Annals New York Academy of Sciences 481, 1-16.
[13] Choquet,, D. and Triller,, A. (2013) The dynamic synapse. Neuron 80, 691-703.
[14] Das,, T. K., Wati,, M. R. and Fatima-Shad,, K. (2015) Oxidative stress gated by Fenton and Haber Weiss reactions and its association with Alzheimer’s Disease. Archives of Neuroscience 2, 1-8.
[15] Davis,, G. W. and Muller,, M. (2015) Homeostatic control of presynaptic neurotransmitter release. Annual Review of Physiology 77, 251-270.
[16] Eom, H. and Song, W. J. (2019) Emergence of metal selectivity and promiscuity in metalloenzymes. Journal of Biological Inorganic Chemistry( In press).
[17] Fischer,, E. H. and Davie,, E. W. (1998) Recent excitement regarding metallothionein. Proceedings National Academy Science USA 95, 3333-3334.
[18] Golgolla, N., Caroni, P., Luthi, A. and Herry, C. (2009) Perineural nets protect fear memories from erasure. Science 325, 12581261.
[19] Hebb,, D.O.( 1949) The Organization of Behavior. Wiley, NewYork.
[20] Huk,, A. and Hart,, E. (2019) Parsing signal and noise in the brain. Science 364, 236-237.
[21] Iwata., M. and Carlson., S. S. (1993) A large chondroitin sulfate proteoglycan has the characteristics of a general extracellular matrix componentofadultbrain. Journal of Neuroscience 13, 195-207.
[22] Juliano,, R. and Haskill,, S. (1993) Signal transduction from extracellular matrix. Journal of Cell Biology 120, 577-585.
[23] Kamali,, P. and Nicholson,, C. (2013) Brain extracellular space: Geometry, matrix and physiologic importance. Basic and Clinical Neuroscience 4, 282-286.
[24] Kägi,, J. H. and Schäffer,, A. (1988) Biochemistry of metallothionein. Biochemistry 27, 8509-8515.
[25] Kandel, E., Schwartz, J., Jessell, T., Siegelbaum, S. and Hudspeth, A. ( Eds) ( 2012) Principles of Neural Science, Fifth Edition. McGrawHill, New York.
[26] Kandel,, E. R., Dudai,, Y. and Mayford,, M. R. (2014) The molecular and systems biology of memory. Cell 157, 163-186.
[27] Katchalski,, E. (1992) Molecular surface recognition: Determination of geometric fit between proteins and their ligands by correlationtechniques. Proceedings of the National Academy of Sciences USA 89, 2195-2199.
[28] Kay,, A. R., Neyton,, J. and Paoletti,, P. (2006) A startling role for synaptic zinc. Neuron 52, 572-574.
[29] Kim, H. Y., Kim, I. T., Kim, G. H., Kim, J. H. and Kang, D. W. (2007) Wet oxidation of mixed resins by a modified Fenton’s reaction with an electrochemical potential. Journal of Industrial and Engineering Chemistry 13, 665-668.
[30] Kim,, J. I., Choi,, D. I. and Kaang,, B. K. (2018) Strengthened connections between engrams encode specific memories. Biochemistry and Molecular Biology Reports 51, 369-370.
[31] Lashley, K. S. ( 1950) In search of the engram. Soc. Experl. Biol. Symp. No. 4. Physiological mechanisms in animal behaviour (pp. 454-482). Cambridge, England, Cambridge University Press.
[32] Lehninger, ( 2008) Principles of Biochemistry 5th Ed. W. H. Freeman, New York
[33] Lobmaier, C., Hawa, G., Götzinger, M., Wirth, M., Pittner, F. and Gabor, F. (2001) Direct monitoring of molecular recognition processes using fluorescence enhancement at colloid-coated microplates. Journal of Molecular Recognition 14, 215-222.
[34] Marx,, G. and Gilon,, C. (2012) The molecular basis of memory. ACS Chemical Neuroscience 3, 633-642.
[35] Marx, G.andGilon,, C.( 2013) Themolecularbasisofmemory.MBM Pt 2: The chemistry of the tripartite mechanism. ACS Chemical Neuroscience 4, 983-993.
[36] Marx,, G. and Gilon,, C. (2014) The molecular basis of memory. Pt 3: Tagging with neurotransmitters (NTs). Frontiers Aging Neuroscience 6, 1-8.
[37] Marx,, G. and Gilon,, C. (2016) The molecular basis of neural memory. MBM Pt 6: Chemical coding of logical and emotive modes. International Journal of Neurology Research 2, 259-268.
[38] Mesulam,, M. M. (1998) From sensation to cognition. Brain 121, 1013-1052.
[39] Mishkin,, M. and Appenzeller,, T. (1987) The anatomy of memory. Scientific American 256, 80-89.
[40] Poo, M., Pignatelli, M., Ryan, T. J., Tonegawa, S., Bonhoeffer, T., Martin, K. C., Rudenko, A., Tsai, L. H., Tsien, R., Fishell, G., Mullins, C., Gonçalves, J. T., Shtrahman, M., Johnston, S. T., Gage, F. H., Dan, Y., Long, J., Buzsáki, G. and Stevens, C. (2016) What is memory ? The present state of the engram. BMC Biology 14, 40
[41] Popescu, B. F. G, Robinson, C. A., Rajput, A., Rajput, A. H., Harder, S. L. and Nichol, H. (2009) Iron, Copper, and Zinc distribution of the cerebellum. Cerebellum 8, 74-79.
[42] Poznanski, R. R., Cacha, L. A., Latif, A. Z. A., Salleh, S. H., Ali, J., Yupapin, P., Tuszynski, J. A. and Tengku, M. A. (2019) Theorizing how the brain encodes consciousness based on negentropic entanglement. Journal of Integrative Neuroscience 18, 1-10.
[43] Pribram,, K. H and Meade,, S. D. (1999) Conscious awareness: processing in the synaptodendritic web. New Ideas in Psychology 17, 205-214.
[44] Reith,, M. E. (2002) Neurotransmitter Transporters: Structure, Function, and Regulation / 2nd ed. Springer-Verlag, New York.
[45] Roshchina, V. V. ( 2010) Evolutionary considerations of neurotransmitters in microbial, plant, and animal cells. In: Microbial Endocrinology, Inter-kingdom Signaling in Infectious Disease and Health, Chapter 2. M. Lyte and P.P.E. Freestone (eds.), Springer, New York.
[46] Roy, D. S, Arons, A., Mitchell, T. I., Pignatelli, M., Ryan, T. J. and Tonegawa, S. (2016) Memory retrieval by activating engram cells in mouse models of early Alzheimers’ disease. Nature 531, 508512.
[47] Santoro, A. and Frankland, P. W. (2014) Chasing the trace. Neuron 84, 243-246.
[48] Schacter,, D. L. (2011) Forgotten Ideas, Neglected Pioneers: Richard Semon and the Story of Memory. Routledge, New York.
[49] Semon,, R. (1923) "Chapter II. Engraphic Action of Stimuli on the Individual". The Mneme. London: George Allen & Unwin. p. 24; trans by Louis Simon.
[50] Schmitt, F. O., Samson, F. E., Irwin, L. N. and Homsy, Y. M. ( eds) ( 1969) Brain cell micro-environment. Neuroscience Research Program, Bethesda, MD.
[51] Squire,, L. and Kandel,, E. (2008) Memory: From Mind to Molecules. 2nd ed. Roberts and Company Publishers, New York.
[52] Suzuki,, K. T., Imura, N. and Kimura, M. ( Eds) ( 1993) Metallothionein III; Biological Roles and Medical Implications. Birkhäuser Velag, Berlin.
[53] Triller,, A. and Choquet,, D. (2005) Surface trafficking of receptors between synaptic and extrasynaptic membranes: "and yet they do move!" Trends in Neuroscience 28, 133-139.
[54] Tosches, M., Yamawaki, T. M., Naumann, R. K., Jacobi, A. A., Tushev, G. and Laurent, G. (2018) Evolution of pallium, hippocampus, and cortical cell types revealed by single-cell transcriptomics in reptiles. Science 360, 881-888.
[55] van, Niel, G., D’Angelo,, G. and Raposo,, G. (2018) Shedding light on the cell biology of extracellular vesicles. Nature Reviews 19, 213-228.
[56] Vargová, L. and Syková, E. (2014). (2014) Astrocytes and extracellular matrix in extrasynaptic volume transmission. Philosophical Transactions of the Royal Society B 369, 1-8.
[57] Vizi, E. S., Fekete, A., Karoly, R. and Mike, A. (2010) Non-synaptic receptors and transporters involved in brain functions and targets of drug treatment. British Journal of Pharmacology 160, 785809.
[58] Vizi,, E. S. (2013) Role of high-affinity receptors and membrane transporters in nonsynaptic communication and drug action in the central nervous system. Pharmacological Reviews 52, 63-89.
[59] Wardman, P. and Candeias, L. P. (1996) Fenton Chemistry: An Introduction. Journal of Radiation Research 145, 523-531.
[60] Warshel,, A. and Levitt,, M. (1976) Theoretical studies of enzymic reactions: dielectric,electrostatic and steric stabilization of the carbonium ion in the reaction of lysozyme. Journal of Mathematical Biology 103, 227-249.
[61] Watson, J., Baker, T. A., Bell, S. A., Gann, A., Levine, M. and Losick, R. (2013) Molecular Biology of the Gene. 7th Edition. Pearson Publishers, New York.
[62] Zhang, Z., Wu, J., Yu, J. and Xiao, J. (2012) A brief review on the evolution of GPCR: conservation and diversification. Pharmacological Reviews 52, 63-89.
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