Restricted Research - Award List, Note/Discussion Page

Fiscal Year: 2014

2053  The University of Texas at San Antonio  (23613)

Principal Investigator: Wilson, Charles

Total Amount of Contract, Award, or Gift (Annual before 2011): $ 281,639

Exceeds $250,000 (Is it flagged?): Yes

Start and End Dates: 7/1/11 <> 4/30/16

Restricted Research: YES

Academic Discipline: BIOLOGY DEPARTMENT  

Department, Center, School, or Institute: UTSA Neurosciences Institute  

Title of Contract, Award, or Gift: ATonically Active Network in the Neostriatum

Name of Granting or Contracting Agency/Entity: National Institutes of Health

Program Title: none
CFDA Linked: Extramural Research Programs in the Neurosciences and Neurological Disorders


Recent advances in the study of human Parkinson's disease and experimental animal models of the disease have directed attention to oscillatory electrical activity in the basal ganglia. Low frequency oscillations, in the beta range (13-30 Hz) have been shown to be associated with bradykinesia. In healthy experimental animals beta oscillations are prominent in the absence of movement, whereas higher frequency gamma range oscillations (above 30 Hz) are observed during movements. These oscillations are measured as field potentials using gross electrodes, so their cellular origins are not known, but they are in part generated in the striatum. Because this is a population measure, it must reflect synchronous activity in groups of neurons. Because they occur in the absence of movements, the oscillatory signals are probably generated by synchrony of among specific types of neurons that are spontaneously active even when there is little or no input to the striatum. One spontaneously active interneuron, characterized by its intrinsic bursting, is the most likely candidate as the generator of these oscillations. These experiments will determine whether the intrinsic resonant properties of that striatal interneuron type is appropriate for generation of oscillations in the beta frequency band, and what determines the degree of synchrony among the cells of this type. Synchronization could be triggered by shared inputs, or by connections among the oscillating neurons, and both of these mechanisms will be tested using neurons in mouse brain slices. There are two kinds of spontaneously active interneurons in the striatum (i.e. active in the absence of excitation from elsewhere). They are the cholinergic interneuron and the LTS (low-threshold spike) bursting interneuron. Together, these two neurons comprise a spontaneously active network in the striatum that generates continuous oscillatory activity, even in the absence of input. These two cell types can be readily identified in slices, and targeted for study. Experiments will determine the mechanism of spontaneous oscillations in LTS cells, and determine whether synaptic connections between them act to increase or prevent synchronous activity. They will also determine the nature of synaptic connections between the cholinergic and LTS cells, and whether these should promote or prevent synchronization. These experiments will reveal mechanisms promoting synchronization that may be points of action of dopaminergic depletion and possible targets for future anti-parkinsonian therapies.

Discussion: No discussion notes


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