Dynamic Neuronal Organizations in Neocortex

Georgetown University, Washington DC

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Abstract

DESCRIPTION (provided by applicant): The long-term objective of this study is to understand the organization of population neuronal events (correlated activities of millions of neurons). This proposal studies the propagation of excitation waves (a.k.a. traveling waves) in the neo-cortex. Propagating waves occur during sensory and motor processes as well as during neurological disorders such as epilepsy. The mechanisms that control the propagating velocity and directions are important in determining what kind of activity patterns will be carried by the wave and delivered to what part of the cortex, and at what time. Very little is known about the control of the propagating direction and velocity. This is because the waves travel in a distributed neuronal network with parallel and polysynaptic pathways. This proposal will test a hypothesis that propagating waves are generated by coupled local oscillators. The phase relationship among the local oscillators determines the velocity and direction. Voltage-sensitive dye imaging will be used to visualize the propagation waves generated in vitro, in neo-cortical slices. Three Specific Aims are proposed to study the local oscillators during two kinds of "theta" (4-12 Hz) oscillations and an evoked gamma oscillation. Aim 1 consists of two experiments. One experiment will visualize the local oscillators and the boundaries between them. The other experiment will try to separate individual local oscillators with micro cuts to the cortical tissue. Aim 2 will test the hypothesis on the two-dimensional waves generated in tangential cortical slices. Aim 3 will study the neuronal-composition of an evoked gamma oscillation. The spiking activity of individual neurons will be optically monitored in an attempt to understand how the activities of individual neurons compose a population oscillation. This study will not only contribute to the understanding of normal cortical processing but also to the understanding of the initiation and spreading of epileptic seizure activity in the cortex that disrupts the life of about 1% of the U.S. population.