Scientists unravel the neuronal metabolism in learning and memory

Reviewed by Emily Henderson, B.Sc.Jul 5 2022

Exploring the predictive properties of neuronal metabolism can contribute to our understanding of how humans learn and remember. This key finding from a consideration of molecular mechanisms of learning and memory conducted by scientists from Russia and the U.S. has been published in Neuroscience & Biobehavioral Reviews.

The emerging trend in neuroscience is to consider the work of neurons as anticipatory and future-oriented, although this approach is not yet mainstream and features in just a few publications. In a paper entitled 'Neuronal metabolism in learning and memory: The anticipatory activity perspective,' Yuri I. Alexandrov, HSE Professor and Head of the V.B. Shvyrkov Laboratory of Psychophysiology at the Russian Academy of Sciences Institute of Psychology, and Mikhail V. Pletnikov, Professor of the Department of Physiology at the State University of New York, University at Buffalo, argue that neurons behave proactively because they strive to survive-; just as all living organisms. Neurons use microenvironmental metabolites as 'food', and neuronal impulse activity is aimed at obtaining these metabolites. Rather than responding to an incoming signal, neurons proactively trigger an influx of needed substances to the cell, such as neurotransmitters.

When a specialized set of our neurons fire together, we act to obtain a behavioral outcome, while the neurons also obtain their own micro-outcome in the form of needed metabolites. This process can be described as metabolic cooperation of cells, involving not only neurons but also glial, somatic, glandular, muscle and other cells throughout the body. This principle of how cells work is central to learning, which essentially means creating systemwide groups of metabolically cooperating cells that drive human behavior."

Yuri Alexandrov, Professor at HSE School of Psychology

The researchers note that for a long time, the 'stimulus-response' paradigm was dominant in the study of molecular mechanisms of learning and memory; it was assumed that just as the entire human body responds to environmental stimuli, neurons respond to incoming impulses which cause excitation of certain parts of the neuron's membrane. The neuron either fires or does not fire, depending on whether or not the excitation reaches a certain threshold.

Back in 1930s–1970s, the Russian physiologist Peter Anokhin developed his theory of functional systems, including the concept of 'integrative activity of neurons', according to which a neuron's excitation causes intraneuronal chemical processes-; rather than a summation of local excitations on the membrane. These chemical processes lead to a neuronal spike.

Building on Anokhin's theory, his student Vyacheslav Shvyrkov and colleagues developed a systems-oriented approach to the study of neurons. However, Anokhin's understanding of the sequence of events was traditional: excitation of a neuron comes first, followed by a response.

'An important recent step in understanding how neurons work has been the idea that a neuron's anticipatory activity, rather than an external impulse, is what comes first. The neuron does not respond to incoming excitation but proactively triggers an influx of activity,' Alexandrov explains.

The authors argue that exploring systemwide intercellular metabolic cooperation as a learning mechanism could be a promising area of focus for further experimental research.

This approach, they believe, could lead to breakthroughs in studying the behavior of malignant cells and in developing new cancer treatments.

'Malignancies consist of cells that metabolically cooperate not only with their immediate environment but also with other cells in the body. We plan to conduct experimental studies to explore tumor cell responses to diametrically opposed individual behaviors, such as striving towards a desirable event or avoiding an undesirable or dangerous one. This can give us insight into how various systemwide cellular integrations impact tumor cells' survival. As a result, we hope to propose an effective approach to influencing tumor cells through human behavior, Alexandrov concludes.