A molecular basis for learning and memory.

Three stages in memory (electrical, short-term and long-term) are reviewed. The short computing time of organized neural systems favors synapses as loci for storage of memory. Transfer of neuronal excitation depends upon transfer of transmitter, involving the steps: vesicle attachment to presynaptic vesicle-release sites, contraction at dithiolate structures of these sites, exocytosis of transmitter, movement of transmitter across synaptic cleft, and reception at postsynaptic sites. Disulfide formation from dithiolates (calcium dithiolate salt) occurs during excitation and can represent a short-term alteration in properties of vesicle-release sites and, thus, short-term memory. Repair by one mechanism of the altered vesicle-release sites through reduction of the disulfide bond returns the system to its original state or, by a second mechanism, enlarges the presynaptic area covered by these sites. Such enlargement is a stable, permanent mode: long-term memory. Suitable concentrations of transmitter at postsynaptic receptor sites lead to mobilization of additional receptor sites through polymerization of monomeric receptor units. Postsynaptic expansion constitutes a metastable long-term storage, readily reconstituted under appropriate stimuli. Reverberations at the electrical stage of memory are suggested as a necessary link to the chemical stage of memory. These ideas constitute the elements of a molecular theory of learning and memory.