The physiology of memory: recordings of things past.

neural development: the recruitment of cellular programs of growth by signaling molecules. These cellular programs can include alterations in the display of cell surface adhesion molecules. For example, long-term sensitization training in Aplysia causes a transcription-dependent down-regulation of NCAM-related cell adhesion molecules on the surface of sensory neurons (18). If this were generally the case, then in a sense, Sperry's circle is squared. Activity initiated by experience could lead to the release of signaling molecules that engage transcriptional control mechanisms, which modulate cell surface receptors so as to regulate cell-cell interactions. The development of stem cell techniques for homologous recombination in mice (19) has provided a useful tool for testing genetically whether a particular mechanism is important for LTP in the hippocampus of the adult organism and whether LTP in the hippocampus is causally required for learning (20). These gene ablation methods can now be extended to determine whether synaptic modulation during development resembles memory storage only phenotypically or whether they actually share common molecular mechanisms (20). We should therefore soon be in a position to see whether solutions to the problems of learning and memory will yield, as an extra bonus, insights into synapse development and vice versa. If the study of learning and synapse development prove to be mutually reinforcing on the molecular level, then the Decade of the Brain, which we hope will relate molecules to mind, will be off to a particularly good start. Our conception of the process of memory how we remember and recognize-is now undergoing a revolution similar to the dramatic changes seen over the past two decades in our understanding of how sensory information is processed. Sensory systems are now known to comprise a large number of separate cortical areas with complex in-terconnections; this complexity replaces the old notion of a primary sensory area with one or two cortical subsidiary areas. Likewise, memory is being fractionated as a result of recent studies-psychological, physiological, and anatomical (1). This fractionation of memory systems was inevitable, as it now appears that most or all of the adult brain undergoes learning-dependent changes. Each biological change contributes to one or more of the numerous memory systems, which are defined behav-iorally or psychologically. One class of memory system underlies declarative, or explicit, memories, which are the memories of specific facts and events. Within this class, it is useful to distinguish short-term (working memory) processes from long-term ones, and …