The physiological approach: functional architecture of working memory and disordered cognition in schizophrenia

The method of single-cell recording in awake behaving monkeys as they perform behavioral tasks is perhaps the most powerful approach to understanding the neural basis of behavior. In contrast to cellular analyses in vitro, e.g., in slice preparations, the in vivo approach allows direct correlation of cellular activity and specific processes as they are isolated by behavioral paradigms. As brain mechanisms are studied under natural conditions, inferences about the dynamic basis of information processing are direct. Limitations of this approach include the inability to unequivocally identify the cell under investigation, though location by cytoarchitectonic area and cortical depth is possible. Neurophysiological studies have not only given a dynamic view of neural processing “on line” but have allowed investigators to examine fundamental issues about normal brain function and dementia. Here I illustrate some of these issues and the power of single cell physiology to address them. Before doing so, it should be patently obvious that recording one cell at a time is a technical necessity and in no way should be taken to imply that any behavior is dependent on a single cell. Rather the neuron investigated is a representative of a cohort of cells acting in aggregate.