Dendritic Signal Integration Underlying Plasticity

Yale University, New Haven CT

Investigators

Abstract

The concomitant activity of neurons in the brain can either potentiate or depress functional connections (synapses) between neurons in a persistent manner. These changes have properties that have made them the premiere cellular model to study regulation of memory mechanisms and learning. The overall aim of this research is to characterize, in dendrites and, for the first time, in dendritic spines of individual neurons, the non-linear and spatially inhomogeneous interactions of membrane potential signals and calcium signals that represent the first fundamental step in the induction of synaptic plasticity. Experiments will be conducted with brain slices prepared from rat hippocampus, a region with an essential role in learning and the establishment of new memories. The dendrites and spines of individual neurons will be explored with a novel imaging technique using a voltage sensitive dye, so that electrical activity can be monitored simultaneously from the entire dendritic arbor. Answers to some of the questions articulated in this project would further our understanding of experience related changes in the strength of functional connections in the brain, and are likely to lead to novel ideas about mechanisms that underlie learning and memory formation. Thus, the results of this analysis will bear on the basic neuroscience of higher nervous activity. The broader impacts of this research will be realized primarily by contributing to better understanding of the brain, thereby promoting the progress of fundamental science. Better understanding of brain mechanisms has clear and widely documented positive effects on developing the most advanced concepts used in information processing and computational technologies which, in turn, have enormous impact on almost all aspects of modern human activities. The impacts of this research will also be realized through teaching and mentoring of graduate and MD/PhD students and by providing opportunities for the participation of underrepresented minorities in research.