This Small Grant Application requests support for research involving the development of new research technology and research approaches. The proposed research combines experiments designed to validate further the use of a novel amperometric choline detection method for the assessment of acetylcholine (ACh) release with studies that will explore the usefulness of this methodology for the test of hypotheses about the functions of plastic, long-term changes of the excitability of the cortical cholinergic input system. The initial experiments will examine the relationships between electrical, including tetanic, stimulation of the cholinergic basal forebrain (BF) and evoked choline signals in the auditory cortex. Additional experiments will determine that evoked choline signals reflect choline derived from hydrolysis of ACh, and from ACh released depolarization-dependently. A second series of experiments will employ this methodology to test hypotheses about the role of cortical ACh release in the mediation of the long-term plastic changes of BF stimulation on auditory cortical input processing. Collectively, this research will achieve two major goals. First, it will generate essential evidence concerning the validity and usefulness of the choline biosensor for the assessment of ACh release at high temporal (milliseconds to seconds) and spatial (um) resolution. Second, present techniques for the assessment of ACh release are of limited use for research requiring information about stimulus-evoked changes in ACh release; however, such information is essential for the test of hypotheses about the role of cholinergic transmission in mediating plastic changes in sensory input processing. The proposed research will test the viability of using the choline microelectrode technique to address this central issue. Moreover, the expected results will be useful for future investigations about the role of the cortical cholinergic input system in modulating the attentional processing of stimuli that acquire behavioral, specifically affective, significance. ? ?
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