What do phasic cholinergic signals do?

Abstract

In addition to the neuromodulatory role of cholinergic systems, brief, temporally discrete cholinergic release events, or “transients”, have been associated with the detection of cues in attention tasks. Here we review four main findings about cholinergic transients during cognitive processing. Cholinergic transients are: 1) associated with the detection of a cue and influenced by cognitive state; 2) not dependent on reward outcome, although the timing of the transient peak co-varies with the temporal relationship between detection and reward delivery; 3) correlated with the mobilization of the cue-evoked response; 4) causal mediators of shifts from monitoring to cue detection. We next discuss some of the key questions concerning the timing and occurrence of transients within the framework of available evidence including: 1) Why does the shift from monitoring to cue detection require a transient? 2) What determines whether a cholinergic transient will be generated? 3) How can cognitive state influence transient occurrence? 4) Why do cholinergic transients peak at around the time of reward delivery? 5) Is there evidence of cholinergic transients in humans? We conclude by outlining future research studies necessary to more fully understand the role of cholinergic transients in mediating cue detection.

Basal Forebrain Cholinergic Circuits and Signaling in Cognition and Cognitive Decline

“…Nicotine has been widely reported to improve performance in specific attention tasks and exposure to nicotine during development can lead to lasting impairments in attention performance and in the brain areas thought to mediate attention (Bloem et al, 2014; Jung et al, 2016). Studies of polymorphisms, mutations, and deletions of various cholinergic genes further link alterations in cholinergic signaling to modified attention performance (Sarter et al, 2016a; Sarter et al, 2016b). Overall, the last 5 years have greatly sharpened our understanding of how cholinergic circuits co-ordinate with both prefrontal and sensory cortices to shape behavior in response to attentional tasks.…”

“…(see text and Reviews by Munoz & Rudy, 2014; Picciotto et al, 2012; Sarter, 2016; Zaborzsky et al, 2015). …”

“…Once a task relevant stimulus is detected in the sensory cortex, cholinergic signaling from the basal forebrain to the PFC is stimulated and transient ACh release within the PFC signals cue detection (Sarter et al, 2016a; Parikh et al, 2007; Howe et al, 2013). …”

The neuroscience of cognitive-motivational styles: Sign- and goal-trackers as animal models.

“…Using diverse research approaches ranging from assessing effects of selective lesions, amperometric measures of the fast, phasic, or transient component of cholinergic neurotransmission, microdialysis measures of levels of cholinergic neuromodulation, neurophysiological recordings, and optogenetic generation and attenuation of fast cholinergic transients in performing rodents, the basal forebrain cholinergic projection system to the cortex has been shown to mediate, necessarily, the incorporation of cues into cortical circuitry, thereby allowing such cues to control behavior (Avery, Dutt, & Krichmar, 2014; Goard & Dan, 2009; Gritton et al, 2016; Howe et al, 2013; Howe et al, 2017; McGaughy et al, 1996; Parikh, Kozak, Martinez, & Sarter, 2007; Pinto et al, 2013; Runfeldt, Sadovsky, & MacLean, 2014; Sarter, Howe, & Gritton, 2015; Sarter, Lustig, Berry, et al, 2016; Sarter, Lustig, Howe, Gritton, & Berry, 2014). Furthermore, levels of cholinergic neuromodulation influence the likelihood and the amplitudes of cholinergic transients that cause the detection of cues in attentional contexts (for a circuitry model underlying this interaction see Hasselmo & Sarter, 2011).…”

Cholinergic genetics of visual attention: Human and mouse choline transporter capacity variants influence distractibility

“…In terms of temporal specificity, there appear to be both phasic (transient) and tonic (neuromodulatory) modes of cholinergic signaling (Gritton et al, 2016; Hasselmo and Sarter, 2011; Howe et al, 2013; Parikh et al, 2007; Sarter, 2015; Sarter and Kim, 2015; Sarter et al, 2014b, 2016). Phasic or “transient” cholinergic signals causally mediate the detection of cues, that is, “the entirety of information concerning the presence of a signal into a system that allows the subject to report the existence of the signal (or cue) by an arbitrary response specified by the experimenter, and that provides feedback about the adequacy/accuracy of the response based on response outcome” (modified from Posner et al, 1980; for discussion of this definition see Sarter et al, 2016). Arguably the strongest demonstration of the function of cholinergic transients in cue detection involves the false detection of cues following optogenetic generation of such transients during non-cued trials, which normally do not result in phasic endogenous acetylcholine (ACh) release events (Gritton et al, 2016).…”