The dilemma of gene-expression models of memory

[Fausto Intilla]

If the cell's genome is altered in memory,then either all the synapses of the neuron are altered or,alternatively,some mechanism exists that enduringly restricts the effect of the new gene product(s) to selected synapses.Both assumptions are problematic.Altering all the synapses following experience-dependent modification of only part of them,seems to be a wasteful way of managing storage capacity.On the face of it the second possibility,namely selective deposition of gene products in individual synapses, is more appealing,and is substantiated by pieces of circumstantial evidence.Polyribosomes in neurons are selectively positioned beneath synaptic junctions,hence providing individual synapses with a protein synthesis machinery (Steward and Levy, 1982).Moreover,dentrites contain a cytoskeletal system for the selective transport of RNA to synaptic sites (Davis et al.1987).However,if novel RNA,or ribosomes,or proteins,are funnelled into only selected synapses,then what marks these synapses in the first place? And if such a primary long-term change occurs in the synapse,why is gene regulation needed at all?

Fausto Intilla
(Inventor-scientific divulgator)

[Fausto Intilla]

Ample evidence indicates that the expression of genes in the mature organism is influenced by the environment.It is ,therefore,tempting to consider a role in memory for alteration in gene expression.Before proceeding to discuss experimental evidence for the macromolecular synthesis hypothesis,I should clarify what role the newly synthesized proteins could have.I assume that these proteins modify properties of neuronal systems,by stabilizing and extending mechanisms used in short-term memory,or by initiating new types of cellular change.Note that the neuronal loci subserving short - and long - term memory are expected to overlap,at least at first,but need not be identical.An example from Aplysia illustrates this:
short term habituation of the GSW reflex was portrayed as homosynaptic depression,but long-term habituation involves additional central neurons and heterosynaptic depression(Montarolo 1988).However,regardless of wich cellular loci are modified in short and long term memory,one point is clear: macromolecules subserve changes in the representational properties of neuronal circuits,but do not directly encode a specific representation.The latter is encoded in the connectivity and molar activity of the circuit.In other words,similar molecular changes may subserve different modifications in different internal representations,depending on the cellular context in wich these molecular changes take place.

[Fausto Intilla]

Dear friends,
the idea is that neuronal memory,similar to genetic memory,is a macromolecular code.In other words,here macromolecules are specific internal representations.This idea emerged against the background of much excitement about breaking the genetic code;it gained much publicity and evoked much debate in the 1960s and 1970s,but has since declined and is currently mainly of historical interest.The "macromolecular code", or the "macromolecular representation" hypothesis,led to an intensive search for macromolecules that encode specific memories;it culminated in claims that such memories can indeed be transferred by brain extracts and peptides from one individual to another,be it in worms,fish,or rodents (Ungar 1970).These claims were not substantiated by data from other groups (Byrne 1966).It is not unlikely that successful "memory transfer" were due to the transfer of hormones,controlling general arousal and fear,from trained to naive individuals.
The macromolecular representation hypothesis made some early and partial contributions to the popularity of other types of experiments,wich tested the correlation of alterations in nucleic acid with neural activity and behavioural experience (Hyden and Egyhazi 1962;Hyden and Lange 1965;Chapouthier 1983),and the effect of macromolecular synthesis inhibitors on learning and memory. The experiments on the effect of macromolecular synthesis inhibition,did propose a role for RNA and protein synthesis in memory.However,the interpretation of the data did not require the assumption that specific memories are encoded in macromolecules.As a matter of fact,most researches engaged in the latter types of experiments did not operate at all within the conceptual framework of "macromolecular representation".

Fausto Intilla
(Inventor-scientific divulgator)

[DrSupriya]

Interested to know more.
DrSupriya