Thomas H. Brown, Ph.D. Stanford 1977

My laboratory studies the mechanisms of learning and memory and their age-related changes. Research ranges from the molecular to the behavioral levels of analysis, with a focus on rapid forms of learning. The medial temporal lobe (MTL) brain structures on which I have concentrated include the hippocampus, amygdala, and perirhinal cortex. Collectively, these MTL structures are implicated in aspects of declarative and emotional memory and they are early targets of neurodegeneration in Alzheimer's disease.

My working hypothesis has been that associative long-term potentiation (LTP) a Hebbian form of synaptic plasticity is responsible for certain rapid forms of associative learning in the MTLs and elsewhere. Accordingly, one long-term research thrust has been to develop techniques that enable a rigorous analysis and understanding of synapses and neurons in these structures, all of which appear to participate in rapid learning. In vitro methods applied to brain slices include current- and voltage clamp analysis, using sharp and whole-cell recordings; quantal analysis; confocal and dual-photon microscopy; Ca2+ imaging; and dual-labeling and anatomical reconstructions of recorded neurons. It now appears that Hebbian synaptic plasticity is widespread throughout phylogeny.

A second long-term research objective has been to understand the causal connections between synaptic and neuronal modifications, the affected circuits, and the resulting behavioral or cognitive changes. In vivo methods include Pavlovian and instrumental conditioning, behavioral neuropharmacology, and behavioral neurophysiology. These experiments can be followed by further in vitro analysis. Computer simulations of synapses, neurons, and circuits are used to evaluate hypotheses, to interpret findings, and to integrate information across different levels of analysis.