Acetylcholine release in prefrontal cortex promotes gamma oscillations and theta–gamma coupling during cue detection

William M. Howe, Howard J. Gritton, Nicholas A. Lusk, Erik A. Roberts, Vaughn L. Hetrick, Joshua D. Berke, Martin Sarter

Research output: Contribution to journalArticlepeer-review


The capacity for using external cues to guide behavior (“cue detection”) constitutes an essential aspect of attention and goal-directed behavior. The cortical cholinergic input system, via phasic increases in prefrontal acetylcholine release, plays an essential role in attention by mediating such cue detection. However, the relationship between cholinergic signaling during cue detection and neural activity dynamics in prefrontal networks remains unclear. Here we combined subsecond measures of cholinergic signaling, neurophysiological recordings, and cholinergic receptor blockade to delineate the cholinergic contributions to prefrontal oscillations during cue detection in rats. We first confirmed that detected cues evoke phasic acetylcholine release. These cholinergic signals were coincident with increased neuronal synchrony across several frequency bands and the emergence of theta–gamma coupling. Muscarinic and nicotinic cholinergic receptors both contributed specifically to gamma synchrony evoked by detected cues, but the effects of blocking the two receptor subtypes were dissociable. Blocking nicotinic receptors primarily attenuated high-gamma oscillations occurring during the earliest phases of the cue detection process, while muscarinic (M1) receptor activity was preferentially involved in the transition from high to low gamma power that followed and corresponded to the mobilization of networks involved in cue-guided decision making. Detected cues also promoted coupling between gamma and theta oscillations, and both nicotinic and muscarinic receptor activity contributed to this process. These results indicate that acetylcholine release coordinates neural oscillations during the process of cue detection.

Original languageEnglish (US)
Pages (from-to)3215-3230
Number of pages16
JournalJournal of Neuroscience
Issue number12
StatePublished - Mar 22 2017
Externally publishedYes


  • Acetylcholine
  • Oscillations
  • Prefrontal cortex

ASJC Scopus subject areas

  • Neuroscience(all)


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