Cortical cholinergic signaling controls the detection of cues

Howard J. Gritton, William M. Howe, Caitlin S. Mallory, Vaughn L. Hetrick, Joshua D. Berke, Martin Sarter

Research output: Contribution to journalArticlepeer-review


The cortical cholinergic input system has been described as a neuromodulator system that influences broadly defined behavioral and brain states. The discovery of phasic, trial-based increases in extracellular choline (transients), resulting from the hydrolysis of newly released acetylcholine (ACh), in the cortex of animals reporting the presence of cues suggests that ACh may have a more specialized role in cognitive processes. Here we expressed channelrhodopsin or halorhodopsin in basal forebrain cholinergic neurons of mice with optic fibers directed into this region and prefrontal cortex. Cholinergic transients, evoked in accordance with photostimulation parameters determined in vivo, were generated in mice performing a task necessitating the reporting of cue and noncue events. Generating cholinergic transients in conjunctionwith cues enhanced cue detection rates. Moreover, generating transients in noncued trials, where cholinergic transients normally are not observed, increased the number of invalid claims for cues. Enhancing hits and generating false alarms both scaled with stimulation intensity. Suppression of endogenous cholinergic activity during cued trials reduced hit rates. Cholinergic transients may be essential for synchronizing cortical neuronal output driven by salient cues and executing cue-guided responses.

Original languageEnglish (US)
Pages (from-to)E1089-E1097
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number8
StatePublished - Feb 23 2016
Externally publishedYes


  • Acetylcholine
  • Attention
  • Cortex
  • Optogenetics

ASJC Scopus subject areas

  • General


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