CRCNS: Dynamics and mechanisms of rhythmic activity in basal ganglia

Indiana University Indianapolis, Indianapolis IN

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): The basal ganglia (BG) are a group of subcortical nuclei receiving extensive projections from cortex and sending extensive projections to thalamus and which are, among other things, involved in neural control of movement. Interest in BG physiology is also motivated by BG-related disorders, especially Parkinson's disease (PD) - a major neurodegenerative disorder characterized by chronic dopamine (DA) deficiency resulting in a set of primarily movement-related symptoms. Although BG plays a significant role in motor control and in motor deficits of PD, the physiological mechanisms responsible for this control and for PD motor deficits remain poorly understood. Recent studies indicate that patterns of oscillatory synchronous activity in BG, although very variable, are strongly relevant to BG physiology and BG disorders, such as PD. The dynamics of these oscillations and their mechanisms are the subjects of this study. Patterns of synchronous oscillatory behavior in spiking units and local field potentials (LFP) will be recorded from BG of human patients and analyzed using a method of synchronous episodes detection. Models, which are adequately constrained by the results of analysis of the variable patterns of synchronous activity recorded from the patients, will be developed. This model will be used as a tool to investigate the mechanisms responsible for the origin of intermittent synchronous behavior and thus identify possible mechanisms in vivo. Bifurcations underlying the occurrence of physiologically realistic dynamics in numerical experiments with the full model and in an analytical approach to a reduced system will be studies. As a result, the mechanisms of the intermittent synchronous activity in BG both in the "biological language" (features of synapses, cells, and connectivity, which give birth to intermittent synchrony) and in "mathematical language" (bifurcations in the system, exhibiting realistic rhythmicity) will be understood. Based on the understanding of the mechanisms, potential methods for modulation and suppression of this rhythmicity (which is believed to be pathological) will be suggested. PUBLIC HEALTH RELEVANCE: The project will enhance understanding of physiology of human brain in Parkinson's disease, a major neurodegenerative disorder. The results of the project may assist in development of new therapies for this disease and related disorders.