BST^* Executive summary prepared by Marina T. Botana¹ and Raymond C. Valentine²

¹ Victoria University of Wellington, New Zealand; m.botana23@gmail.com ; +64-27-3799404

² Professor Emeritus, University of California, Davis, CA 95616, USA; valentine.ray@gmail.com ; +1-802-2752980

September 23rd, 2021

Short-term memory is trained and stored in reflex arcs in spinal neurons, which obey “use it or lose it rule”

When a stimulus is repeated at regular intervals, two adaptations occur in the reflex arc (Fig.1) response—sensitization and habituation. Sensitization is an increase in response. Usually, it occurs during the first 10 to 20 responses. Habituation is the opposite and results in a decrease in response. Loss of response continues until the response is extinguished. Without repeated stimulation, synaptic functions regress and reflex responses return to their original state. Several additional important general properties of reflex arcs are as follows:

§ Reflex arc transmissions are extremely fast, up to 200 miles per hour.

§ The signal to fire a reflex arc is directly activated by a specialized sensor—not the brain--and, therefore, is not conscious.

The neural circuitry through a reflex arc involves several different classes of axons. For example, when accidently touching a hot stove, reflex arc responds and damage to the body is minimized. The brain is notified secondarily, and with repetition, a long-term memory message to be careful when entering a room with a hot stove becomes hard-wired. Interestingly, young chicks, that have never seen a hawk, run for cover when the shadow of a hawk passes over them. This is an example of a genetically programmed reflex response.

Components of the reflex arc:

The simplest functional unit of the human nervous system is a reflex arc as discussed above. The essential components of the reflex arc are the following:

§ Sensory receptor of a sensory neuron (detects stimulus)

§ Interneuron (connector)

§ Motor neuron

§ Target muscle

The sensory receptor of a sensory neuron detects the signal/stimulus and converts the information into an action potential that is transmitted over the axon of a sensory neuron. The sensory neuron body is in the dorsal root ganglion. The axon of the root ganglion terminates at the dorsal horn, where it synapses with an interneuron. In turn, this interneuron synapses in the interior or ventral horn of the spinal cord with a motor neuron. The action potential is carried by the motor neuron, which exits the spinal cord and synapses with the muscle or gland that orchestrates the response. Reflex arcs can be classified according to the number of synapses, say from one to four. Interestingly, monosynaptic reflex arcs complete a circuit in about 0.02 seconds. This fast muscle response is involuntary, and the brain is not involved.

Discussion: a unified biochemical concept of short- and long-term memory would be valuable?

The biochemical basis of both short- and long-term memory is in its infancy. Our dataset contains two leads, which have already appeared on the radar screen and have stimulated some out-of-the-box unified thinking about mechanisms of memory. Several topics for future research are listed below.

Q&A:

1. Did memory evolve in a modular fashion?

We believe that memory systems coevolved with the first life forms and continued until today.

2. What was the role of Darwinian selection in short term memory?

In other words, the remarkable human brain owes its existence to Darwinian selection. We suggest that in the earliest cells and viruses’ memory was primitive but beneficial and grew in complexity one module at a time. One of the greatest advantages of such modular evolution is that it is relatively easy to mix and match different modules and combinations of modules. For example, we suggest that the matching of sensory perception modules with biological hydrogels was a critical tipping point in the evolution of human memory.

3. Does COVID-19 have memory?

Our short answer is “yes,” with the caveat that genomic/biochemical/physiological analyses are consistent with the evolution of three different sensory modules paired perhaps with only one class of biological gel/solid-state semiconductor. This scenario likely applies to other molecular species of human lipid viruses. The class of sensory modules identified in membranes of COVID-19 is by far the most primitive form of biosensors from a biochemical perspective. These so-called sensors belong to a large and well-studied class of antimicrobial peptides (AMPs), many of which can rapidly depolarize and kill target organisms.

4. Can the synapse of a reflex arc be trained?

It is well known that synapses can be trained. Synapses of reflex response systems are no exception. A one-synapse reflex arc, such as the kneejerk response, is an ideal tool to research unanswered questions on the molecular basis of synaptic training.

5. Is sensory reception the first essential module of a memory arc?

Yes, we believe, that the sensory reception module is the first essential module of a memory arc.

6. Nepalese Monks can consciously control heart rate; what method do they use?

Monks in Nepal spend a significant part of their life meditating, reaching a point at which they can consciously modulate their heartbeat.

We believe that Darwinian selection has honed memory systems, for perhaps billions of years. We propose that memory molecules coevolved with the first life on earth, eventually leading to one of the fittest brains in the biosphere—the human brain. According to this hypothesis, memory systems started out being simple or rudimentary in structure/function and gradually increased in complexity and efficiency. Finally, we highlight a recent publication that we believe has revolutionary potential in the field of periplasmic memory electro biochemistry:

Meysman, F. J. R., R. Cornelissen, S. Trashin, et al., (2019). A highly conductive fibre network enables centimetre-scale electron transport in multicellular cable bacteria. Nature Communications 10:4120. doi: 10.1038/s41467-019-12115-7.

This paper’s data document a quantum leap in complexity of periplasmic mechanisms of energy transduction important for understanding memory storage in hydrogels of Gram-negative bacteria. This is our interpretation of these exciting data, which stand solidly on their own excellent and timely merits.