title: Prefrontal cholinergic mechanisms instigating shifts from monitoring for cues to cue-guided performance: converging electrochemical and fMRI evidence from rats and humans.
abstract: We previously reported involvement of right prefrontal cholinergic activity in veridical signal detection. Here, we first recorded real-time acetylcholine release in prefrontal cortex (PFC) during specific trial sequences in rats performing a task requiring signal detection as well as rejection of nonsignal events. Cholinergic release events recorded with subsecond resolution ("transients") were observed only during signal-hit trials, not during signal-miss trials or nonsignal events. Moreover, cholinergic transients were not observed for consecutive hits; instead they were limited to signal-hit trials that were preceded by factual or perceived nonsignal events ("incongruent hits"). This finding suggests that these transients mediate shifts from a state of perceptual attention, or monitoring for cues, to cue-evoked activation of response rules and the generation of a cue-directed response. Next, to determine the translational significance of the cognitive operations supporting incongruent hits we used a version of the task previously validated for use in research in humans and blood oxygenation level-dependent (BOLD)-functional magnetic resonance imaging. Incongruent hits activated a region in the right rostral PFC (Brodmann area 10). Furthermore, greater prefrontal activation was correlated with faster response times for incongruent hits. Finally, we measured tissue oxygen in rats, as a proxy for BOLD, and found prefrontal increases in oxygen levels solely during incongruent hits. These cross-species studies link a cholinergic response to a prefrontal BOLD activation and indicate that these interrelated mechanisms mediate the integration of external cues with internal representations to initiate and guide behavior.
authors.affiliation: Department of Psychology and Neuroscience Program, University of Michigan, Ann Arbor, Michigan 48109-1043, USA.
authors.forename: William M
authors.initials: WM
authors.lastname: Howe
authors.forename: Anne S
authors.initials: AS
authors.lastname: Berry
authors.forename: Jennifer
authors.initials: J
authors.lastname: Francois
authors.forename: Gary
authors.initials: G
authors.lastname: Gilmour
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Carp
authors.forename: Mark
authors.initials: M
authors.lastname: Tricklebank
authors.forename: Cindy
authors.initials: C
authors.lastname: Lustig
authors.forename: Martin
authors.initials: M
authors.lastname: Sarter
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000818:Animals; D001288:Attention / Q000502:physiology*; D002794:Choline / Q000378:metabolism; D003463:Cues; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008839:Microelectrodes; D010100:Oxygen / Q000097:blood / Q000378:metabolism; D017397:Prefrontal Cortex / Q000098:blood supply* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017603:Signal Detection, Psychological / Q000502:physiology*; D055815:Young Adult
chemical_list: D002794:Choline; D000109:Acetylcholine; D010100:Oxygen