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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Small Research Grants (R03)
Project #
5R03MH073600-02
Application #
7014075
Study Section
Special Emphasis Panel (ZRG1-IFCN-A (90))
Program Officer
Freund, Michelle
Project Start
2005-02-07
Project End
2008-01-31
Budget Start
2006-02-01
Budget End
2008-01-31
Support Year
2
Fiscal Year
2006
Total Cost
$74,418
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Sarter, Martin; Martinez, Vicente; Kozak, Rouba (2009) A neurocognitive animal model dissociating between acute illness and remission periods of schizophrenia. Psychopharmacology (Berl) 202:237-58
Parikh, Vinay; Sarter, Martin (2008) Cholinergic mediation of attention: contributions of phasic and tonic increases in prefrontal cholinergic activity. Ann N Y Acad Sci 1129:225-35
Sarter, Martin (2008) The substantia innominata remains incognita: pressing research themes on basal forebrain neuroanatomy. Brain Struct Funct 213:11-5
Giuliano, Chiara; Parikh, Vinay; Ward, Josh R et al. (2008) Increases in cholinergic neurotransmission measured by using choline-sensitive microelectrodes: enhanced detection by hydrolysis of acetylcholine on recording sites? Neurochem Int 52:1343-50
Sarter, Martin (2007) Cholinergic control of attention to cues guiding established performance versus learning: theoretical comment on Maddux, Kerfoot, Chatterjee, and Holland (2007). Behav Neurosci 121:233-5
Parikh, Vinay; Kozak, Rouba; Martinez, Vicente et al. (2007) Prefrontal acetylcholine release controls cue detection on multiple timescales. Neuron 56:141-54
Briand, Lisa A; Gritton, Howard; Howe, William M et al. (2007) Modulators in concert for cognition: modulator interactions in the prefrontal cortex. Prog Neurobiol 83:69-91
Sarter, Martin; Bruno, John P; Parikh, Vinay (2007) Abnormal neurotransmitter release underlying behavioral and cognitive disorders: toward concepts of dynamic and function-specific dysregulation. Neuropsychopharmacology 32:1452-61
Sarter, Martin (2006) Preclinical research into cognition enhancers. Trends Pharmacol Sci 27:602-8
Sarter, Martin; Gehring, William J; Kozak, Rouba (2006) More attention must be paid: the neurobiology of attentional effort. Brain Res Rev 51:145-60

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