Abstract

This application is a revised competitive renewal application. The overall goal of this interdisciplinary research program is to determine the cognitive functions of cortical cholinergic inputs and their efferent and afferent neuronal circuits. This research integrates contemporary behavioral, neurochemical, and neuro physiological approaches to establish precise relationships between attentional processes and the activity of cortical cholinergic inputs and the cholinergic modulation of cortical information processing. Research conducted during the initial funding period substantiated hypotheses concerning the necessity of cortical cholinergic inputs for attention performance, the specificity of attentional performance associated changes in cortical acetylcholine (ACh) release, and performance-associated and ACh-mediated changes in cortical neuronal activity. The proposed research will continue to exploit the heuristic power of this multidisciplinary research approach in order to test hypotheses about the precise relationship between attentional performance and cortical ACh efflux, the role of prefrontal cortical (PFC) cholinergic inputs in mediating performance-associated desynchronization of PFC neuronal activity, the role of PFC cholinergic inputs in regulating attentional performance-associated changes in ACh release in the posterior parietal cortex (PPC), and the contribution of prefrontal projections to the basal forebrain to the attention performance-associated activation of the PPC. The results of this research are expected to yield a precise determination of the variables of attentional performance that activate cortical cholinergic inputs, the role of cholinergic inputs in prefrontal information processing, and to substantiate hypotheses indicating a crucial role of PFC cholinergic inputs in the performance-associated activation of the 'anterior attention system' and the resulting top-down modulation of cholinergic activity in posterior cortical regions. ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
7R01NS037026-07
Application #
6968994
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Babcock, Debra J
Project Start
1998-09-20
Project End
2007-03-31
Budget Start
2004-09-01
Budget End
2005-03-31
Support Year
7
Fiscal Year
2004
Total Cost
$195,221
Indirect Cost

  Institution

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

  Publications

Parikh, Vinay; St Peters, Megan; Blakely, Randy D et al. (2013) The presynaptic choline transporter imposes limits on sustained cortical acetylcholine release and attention. J Neurosci 33:2326-37
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
Broussard, John I; Karelina, Kate; Sarter, Martin et al. (2009) Cholinergic optimization of cue-evoked parietal activity during challenged attentional performance. Eur J Neurosci 29:1711-22
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
Kozak, Rouba; Martinez, Vicente; Young, Damon et al. (2007) Toward a neuro-cognitive animal model of the cognitive symptoms of schizophrenia: disruption of cortical cholinergic neurotransmission following repeated amphetamine exposure in attentional task-performing, but not non-performing, rats. Neuropsychopharmacology 32:2074-86
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
Brooks, Julie M; Sarter, Martin; Bruno, John P (2007) D2-like receptors in nucleus accumbens negatively modulate acetylcholine release in prefrontal cortex. Neuropharmacology 53:455-63
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

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