Early speculations on the operational nature of memory have been based
upon relatively little experimental evidence. Charles Darwin observed
that domestic rabbits had smaller brains than their wild counterparts,
and attributed this to lack of exercise of their intellect, senses, and
voluntary movements. Unfortunately, subsequent studies of the brains of
men with greatly differing intellectual capability did not substantiate
the hypothesis. Idiots sometimes had larger brains than geniuses. Later,
an idea proposed by Ramon y Cajal came into favor. Since brain cells did
not increase in number after birth, he proposed that memory involved the
establishment of new and more extended intercortical connections.
Unfortunately, methods were not available to test this hypothesis
adequately and it has remained until quite recently in the realm of
conjecture.
Another major hypothesis was that there were two or more stages in the
information storage process. The final form the information took in the
brain was called a brain engram, or memory trace. However, prior to the
formation of the engram, a transitory process denoted as
"reverberational memory" was postulated to exist for a relatively short
time (minutes to hours) (refs. [ref.106] and [ref.107]). This hypothesis
was used by Pauling to explain why an elderly chairman of a board could
brilliantly summarize a complex 8-hour meeting and yet, after its
conclusion and his return to his office, not even remember having
attended the meeting. Thus, this individual’s reverberational memory
functioned well, but advanced years had seriously impaired his brain’s
ability to form a permanent engram. Similar, although less dramatic,
observations in other situations are not uncommon. A wide variety of
experiments have been conducted to study this aspect of memory and to
relate it to the process whereby the information is transformed to a
more stable form (refs. [ref.110]-[ref.112]).
More recently, the concept of a specific biochemical activity during the
process of long-term storage of information has gained considerable
favor. Initially, neither the site nor the nature of the change was well
defined. Quite recent studies by Krech et al. (refs. [ref.113] and
[ref.114]), Bennett et al. ([ref.115]), Rosenzweig et al. (refs.
[ref.116] and [ref.117]) support the view that alteration of the levels
of acetylcholinesterase at cortical synapses play an important role in
information storage. These studies will be discussed in a later section.
However, these authors do not claim that the changes observed are
unambiguously related to the storage of memory. It may well be that the
alterations observed are in some way related to this process but are
still secondary to some other, more basic, process.
An alternative hypothesis is that the information resides in its
ultimate form in some more central structure of the neurone than the
synapse. (It has even been postulated that the basic information is
stored in nonneuronocortical material.) Perhaps Halstead was the first
to postulate the involvement of nucleoprotein in this process
([ref.107]). From the biochemist’s point of view, this is an extremely
attractive hypothesis. Both proteins and nucleic acids possess
sufficient possible permutations of structure to permit storage of a
lifetime’s accumulation of information in an organ the size of the
brain. From the previously known ability of the nucleic acids to code
genetic information, they are the prime suspects. However, from the
known regulatory ability of nucleic acids in specific protein synthesis,
it is possible that the final repository is protein.