title: Cholinergic genetics of visual attention: Human and mouse choline transporter capacity variants influence distractibility.
abstract: The basal forebrain cholinergic projection system to the cortex mediates essential aspects of visual attention performance, including the detection of cues and the response to performance challenges (top-down control of attention). Higher levels of top-down control are mediated via elevated levels of cholinergic neuromodulation. The neuronal choline transporter (CHT) strongly influences the synthesis and release of acetylcholine (ACh). As the capacity of the CHT to import choline into the neuron is a major, presynaptic determinant of cholinergic neuromodulation, we hypothesize that genetically-imposed CHT capacity variation impacts the balance of bottom-up versus top-down control of visual attention. Following a brief review of the cognitive concepts relevant for this hypothesis, we describe the key results from our research in mice and humans that possess genetically-imposed changes in choline uptake capacity. CHT subcapacity is associated with poor top-down attentional control and attenuated (cholinergic) activation of right frontal regions. Conversely, mice overexpressing the CHT, and humans expressing a CHT variant hypothesized to enhance choline transporter function, are relatively resistant to challenges of visual attention performance. Genetic or environmental modulation of CHT expression and function may be associated with vulnerabilities for cognitive disorders.
authors.affiliation: Department of Psychology and Neuroscience Program, University of Michigan, Ann Arbor, USA. Electronic address: msarter@umich.edu.
authors.forename: Martin
authors.initials: M
authors.lastname: Sarter
authors.affiliation: Department of Psychology and Neuroscience Program, University of Michigan, Ann Arbor, USA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Lustig
authors.affiliation: Department of Biomedical Sciences and Brain Institute, Florida Atlantic University, Boca Raton, FL, USA.
authors.forename: Randy D
authors.initials: RD
authors.lastname: Blakely
authors.affiliation: Department of Psychology and Neuroscience Program, University of Michigan, Ann Arbor, USA.
authors.forename: Ajeesh
authors.initials: A
authors.lastname: Koshy Cherian
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001288:Attention; D014644:Genetic Variation; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D014796:Visual Perception / Q000235:genetics*
chemical_list: D026901:Membrane Transport Proteins; C065637:choline transporter; D000109:Acetylcholine
keywords: Acetylcholine; Attention; Choline transporter; Genetics; Humans; Rodents