2. Short-Term Memory
A train of impulses simply travelling on a long fiber may, for example, be regarded as a short-term memory much in the same way as a delay line acts as a transient memory in a computer. A similar but slightly longer term memory may also be thought of to exist in the form of waves circulating in closed loops [(23)]. In fact, it is almost universally held today that most significant memory occurs in two basic interrelated ways. First of all, such a short-term circulating, reverberatory or regenerative memory which, however, could not conceivably persist through such things as coma, anesthesia, concussion, extreme cold, deep sleep and convulsive seizures and thus, secondly, a long-term memory trace which must somehow reside in a semipermanent fine-structural change. As [Hebb (9)] stated, “A reverbratory trace might cooperate with a structural change and carry the memory until the growth change is made.”
3. The Synapse
The current most highly regarded specific conception of the synapse is largely due to and has been best described by [Eccles (5)]: “ ... the synaptic connections between nerve cells are the only functional connections of any significance. These synapses are of two types, excitatory and inhibitory, the former type tending to make nerve cells discharge impulses, the other to suppress the discharge. There is now convincing evidence that in vertebrate synapses each type operates through specific chemical transmitter substances ...”. In response to a presentation by [Hebb (10)], Eccles was quoted as saying, “One final point, and that is if there is electrical interaction, and we have seen from Dr. Estable’s work the complexity of connections, and we now know from the electronmicroscopists that there is no free space, only 200 Å clefts, everywhere in the central nervous system, then everything should be electrically interacted with everything else. I think this is only electrical background noise and, that when we lift with specific chemical connections above that noise we get a significant operational system. I would say that there is electrical interaction but it is just a noise, a nuisance.” Eccles’ conclusions are primarily based on data obtained in the peripheral nervous system and the spinal cord. But there is overwhelming reason to expect that cellular interactions in the brain are an entirely different affair. For example, “The highest centres in the octopus, as in vertebrates and arthropods, contain many small neurons. This finding is such a commonplace, that we have perhaps failed in the past to make the fullest inquiry into its implications. Many of these small cells possess numerous processes, but no axon. It is difficult to see, therefore, that their function can be conductive in the ordinary sense. Most of our ideas about nervous functioning are based on the assumption that each neuron acts essentially as a link in some chain of conduction, but there is really no warrant for this in the case of cells with many short branches. Until we know more of the relations of these processes to each other in the neuropile it would be unwise to say more. It is possible that the effective part of the discharge of such cells is not as it is in conduction in long pathways, the internal circuit that returns through the same fiber, but the external circuit that enters other processes, ...” [(3)].
4. Inhibition
The inhibitory chemical transmitter substance postulated by Eccles has never been detected in spite of numerous efforts to do so. The mechanism(s) of inhibition is perhaps the key to the question of cellular interaction and, in one form or another, must be accounted for in any adequate theory.
Other rather specific forms of excitation and inhibition interaction have been proposed at one time or another. Perhaps the best example is the polar neuron of [Gesell (8)] and, more recently, [Retzlaff (18)]. In such a concept, excitatory and inhibitory couplings differ basically because of a macroscopic structural difference at the cellular level; that is, various arrangements or orientation of intimate cellular structures give rise to either excitation or inhibition.
5. Long-Term Memory
Most modern theories of semipermanent structural change (or engrams, as they are sometimes called) look either to the molecular level or to the cellular level. Various specific locales for the engram have been suggested, including [(1)] modifications of RNA molecular structure, [(2)] changes of cell size, synapse area or dendrite extensions, [(3)] neuropile modification, and [(4)] local changes in the cell membrane. There is, in fact, rather direct evidence of the growth of neurons or their dendrites with use and the diminution or atrophy of dendrites with disuse. The apical dendrite of pyramidal neurones becomes thicker and more twisted with continuing activity, nerve fibers swell when active, sprout additional branches (at least in the spinal cord) and presumably increase the size and number of their terminal knobs. As pointed out by [Konorski (11)], the morphological conception of plasticity according to which plastic changes would be related to the formation and multiplication of new synaptic junctions goes back at least as far as Ramon y Cajal in 1904. Whatever the substrate of the memory trace, it is, at least in adults, remarkably immune to extensive brain damage and as [Young (24)] has said: “ ... this question of the nature of the memory trace is one of the most obscure and disputed in the whole of biology.”