The "Memory" Effect in a Chain of Biochemical Reactions with a Positive Feedback is Enhanced by Substrate Saturation Described by Michaelis-Menten Kinetics

Bull Math Biol. 2019 Mar;81(3):919-935. doi: 10.1007/s11538-018-00541-5. Epub 2018 Dec 10.

Abstract

Information in the brain is stored in a form of an altered synaptic strength between neurons. The long-term potentiation (LTP), a phenomenon when a short-term increase in neural activity is transformed into a long-lasting increase in strengths of synaptic connectivity, provides an experimental substrate of memory. Using reaction-diffusion equations, we established an LTP model, describing the dynamics of glutamate (Glu), calcium (Ca2+) and nitric oxide (NO) in response to the stimulus-a presynaptic action potential. NO can diffuse to the presynaptic terminal and facilitate the Glu release forming a positive feedback loop. Therefore, the LTP can be considered as a chain of biochemical reactions with a positive feedback loop. In this study, we investigated numerically the role of interactions in a chain of biochemical reactions with a positive feedback on the bistable behavior or memory. We conclude that the positive feedback system with the linear interaction between substances does not exhibit a bistable behavior. However, introduction of substrate saturation described by Michaelis-Menten kinetics for NO decay can lead to an increase in synaptic strength lasting for dozens or even hundreds of seconds. Our finding extends a possible role of NO in LTP: a short high intensity stimulus is "memorized" as a long-lasting elevation of NO concentration.

Keywords: Long-term potentiation; Memory; Michaelis–Menten kinetics; Modeling; Positive feedback; Reaction–diffusion equations.

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Biochemical Phenomena
  • Calcium Signaling / physiology
  • Feedback, Physiological
  • Glutamic Acid / physiology
  • Kinetics
  • Linear Models
  • Long-Term Potentiation / physiology*
  • Mathematical Concepts
  • Memory / physiology
  • Models, Neurological*
  • Nitric Oxide / physiology
  • Nonlinear Dynamics
  • Presynaptic Terminals / physiology
  • Rats

Substances

  • Nitric Oxide
  • Glutamic Acid