Discovery of genes involved with learning and memory: An experimental synthesis of Hirschian and Benzerian perspectives

The biological bases of learning and memory are being revealed today with a wide array of molecular approaches, most of which entail the analysis of dysfunction produced by gene disruptions. This perspective derives both from early “genetic dissections” of learning in mutant Drosophila by Seymour Benzer and colleagues and from earlier behavior-genetic analyses of learning and in Diptera by Jerry Hirsch and coworkers. Three quantitative-genetic insights derived from these latter studies serve as guiding principles for the former. First, interacting polygenes underlie complex traits. Consequently, learning/memory defects associated with single-gene mutants can be quantified accurately only in equilibrated, heterogeneous genetic backgrounds. Second, complex behavioral responses will be composed of genetically distinct functional components. Thus, genetic dissection of complex traits into specific biobehavioral properties is likely. Finally, disruptions of genes involved with learning/memory are likely to have pleiotropic effects. As a result, task-relevant sensorimotor responses required for normal learning must be assessed carefully to interpret performance in learning/memory experiments. In addition, more specific conclusions will be obtained from reverse-genetic experiments, in which gene disruptions are restricted in time and/or space.

The resource consumption principle: attention and memory in volumes of neural tissue.

In the cerebral cortex, the small volume of the extracellular space in relation to the volume enclosed by synapses suggests an important functional role for this relationship. It is well known that there are atoms and molecules in the extracellular space that are absolutely necessary for synapses to function (e.g., calcium). I propose here the hypothesis that the rapid shift of these atoms and molecules from extracellular to intrasynaptic compartments represents the consumption of a shared, limited resource available to local volumes of neural tissue. Such consumption results in a dramatic competition among synapses for resources necessary for their function. In this paper, I explore a theory in which this resource consumption plays a critical role in the way local volumes of neural tissue operate. On short time scales, this principle of resource consumption permits a tissue volume to choose those synapses that function in a particular context and thereby helps to integrate the many neural signals that impinge on a tissue volume at any given moment. On longer time scales, the same principle aids in the stable storage and recall of information. The theory provides one framework for understanding how cerebral cortical tissue volumes integrate, attend to, store, and recall information. In this account, the capacity of neural tissue to attend to stimuli is intimately tied to the way tissue volumes are organized at fine spatial scales.