These recordings indicated enhanced synchronous activity at gamma frequencies during cue detection. However, we also found that cue detection on incongruent hits coincided Stem Cell Compound Library datasheet with more synchronised gamma activity that was sustained through the reward period consistent with the timeline noted for long-lasting cholinergic transients (Howe et al., 2011). Thus, we hypothesise that the increased gamma power

during incongruent hits, reflecting the postsynaptic impact of combined glutamatergic–cholinergic activity, relays the local processing of the cue across a distributed network that in turn recruits the circuitry required to execute the motor response. In the absence of a cholinergic transient, gamma synchrony is attenuated, the likelihood for a successful attentional mode shift is reduced, and cues in such trials are more likely to be missed. The hypotheses described above align with the idea that cortical circuitry integrates the ascending Alectinib in vitro cholinergic system into local circuitry to support cognitive operations

(Fig. 1). Stimulation of intracortical and efferent neurons by cholinergic transients, in conjunction with glutamatergic activity, increases synchronous high-frequency oscillatory activity (as described above). Such enhanced coordination of local activity fosters the formation of cell assemblies to relay output across a distributed network in support of cue detection (see also Fan et al., 2007; Gulledge et al., 2009) and, more generally, the ability of such a cue to control behavior (Engel & Singer, 2001; Rodriguez et al., 2004, 2010; Fries, 2005; Briggs et al., Cyclin-dependent kinase 3 2013). In the absence of cholinergic transients and synchronous high-frequency activity, hit rates are predicted to be reduced, specifically in cued trials requiring an attentional mode shift. Our hypothesis has been deduced from recordings in rats performing the SAT and thus suggests a cortical cholinergic function required for a specific cognitive operation that underlies SAT trial-sequence-based

performance. However, this hypothesis may be readily generalised to other cognitive operations involving cue detection and cue-directed behavior. For example, in rats performing a cross-modal divided-attention task (McGaughy et al., 1994), cholinergic activity is necessary for shifting between cues of different modalities but not for shifting between cues within modalities (see also Turchi & Sarter, 1997). Although cholinergic transients in animals performing this task have not been recorded, the present data would predict that cues involving cross-modal shifts likewise generate cholinergic transients to orchestrate cue-related processing (see also Senkowski et al., 2008; Schneider et al., 2011).