How a Memory May Be a Number and an Organism May Be Digitally Controlled: Considerations of a Systems Analyst Peeking at the Inner Machinery of Long-Term Memory|
Marchetti, C., 1999
IIASA Contract 98-105, International Institute for Applied Systems Analysis, Laxenburg, Austria
Among the various types of memory that may exist I single out for study the long-term one. I apply techniques of systems analysis to produce a credible and self-consistent picture of the process, taking hints from the immense amount of experimental work in the field. Papers connected in one way or another to the problem of long-term memory may number 100,000.
I put to work in appropriately complex tasks three actors that did not seem yet to have found the complex role they deserve, spike trains, kinase II, and dendritic spines. With their integration, everything seems to fall into place, not a proof, but certainly a good omen. I hope I elevate a few keywords and provide a theoretical context for new experiments, if some attention is raised by this work.
I hypothesize that spike trains are digital signals (binary numbers) that activate digitally codable gates. These gates take the form of kinase II molecules which are capable to assume a very large number of configurations. I further hypothesize that kinase II is in fact a counter that can be preset to a given number by a spike train and later activated by spike trains carrying a number with appropriate coding . The process of memory can then be described as four steps:
1) coding of kinase II into a certain configuration corresponding to a number presented in synchrony with an event, e.g., by a central clock via a spike train;
2) conservation of a certain amount of the coded kinase II into a dendritic spine;
3) activation of this kinase II with a spike train carrying the appropriate number; and
4) squirting of Ca2+ from the spine into the dendritic space, activating the synapse. The Ca2+ is produced in the spine by the action of the kinase on associated calmodulin (CaMKII complex)
In summary, the physical seat of long-term memory is in the spines that cover the surface of each dendrite by the hundreds, each spine holding kinase II counters that, in a sense, freeze the reference number of an event. A set of spines, eg a million, that hold counters set on the same number define the neuronal topography of the event.
A recall is the repetition of an event, through the reactivation of a sufficient number of neural circuits that participated to it.. The mechanism delineated is capable of synchronous reactivation of the set of synapses that participated in a given event just by a recall on the coded kinases II through a spike train with the appropriate code number.
If sufficient family resemblance exists between kinase II and kinases C in general, one may speculate that kinases C, which mediate action in a vast number of events, may too be activated by similar procedures. This view would offer the exciting perspective of a central controller dispatching its orders all over the organism in digital form, a virtual Morse Code of life.
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