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NIH Grant
MH 64711-01
Summary
Individual neurons and neural networks are responsible for the generation of behavior. In this process a seeming paradox emerges: activity is both flexible and stable at the same time. It is flexible to respond to perturbations, to learn, to grow, and in general to change. However, the nervous system and its parts simultaneously retain an identity. That is, neuronal activity remains stable and characteristic and the nervous system and its parts are often capable of homeostatically restoring their properties after an insult. Several mechanisms allow this dual function to be expressed, the best studied of which is perhaps synaptic plasticity. However, a different mechanism is emerging as a powerful candidate to perform this dual function: activity-dependent regulation of voltage-sensitive ionic currents.
This project aims to elucidate the cellular mechanisms that allow a neural network to produce stable output while retaining the flexibility to respond to perturbations. A series of experiments is described that are designed to study the properties of this poorly understood mechanism of neuronal activity regulation. Ionic currents control neuronal electrical activity, and their activity-dependent regulation closes a homeostatic regulatory loop on themselves. This mechanism is potentially of great importance as it may underlie a new form of learning and memory via its stabilizing effect on neural network activity.
In this study the regulation of activity in a small and well characterized neural network, as well as the role of long-term activity-dependent regulation of ionic currents in this process will be investigated. The experimental methodology includes several different modes of electrophysiological recording on neurons in the intact network in vitro and in vivo, in dissociated cells in culture and in long-term culture of the whole network. Pharmacological manipulations as well as RNA injections of recently cloned ionic channels are used to modify the expression of endogenous ionic currents. Funding is requested for some equipment, supplies, and the salaries of 2 graduate students, a postdoc and part of the project director's salary.
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