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Cholinergic-dependent shifts to cue-directed behavior.

Phillips KB, Sarter M (2016) Cholinergic-dependent shifts to cue-directed behavior. Neuroscience 2016 Abstracts 833.11 / HHH30. Society for Neuroscience, San Diego, CA.

Summary: Successful cue detection requires cortical cholinergic signaling. Recent evidence has elucidated the role of phasic, short-timescale, regionally-specific cholinergic signals, termed “cholinergic transients”, in cue detection. Cholinergic transients in the right prefrontal cortex were exclusively observed in trials in which cues were detected and when such trials followed non-cued trials yielding correct rejections or falsely perceived non-cued trials (cues that were missed). Thus, these cholinergic transients were interpreted as mediating shifts from performance guided by internally-guided attention to cued-directed behavior (Howe et al., 2013). In contrast to cholinergic transients mediating shift-hits, such transients were not observed during consecutive hits. Transients may be actively suppressed during consecutive hits in order to constrain a potential detection bias and maintain behavioral flexibility (Sarter et al., 2015). Here we removed cholinergic innervation to the right prefrontal cortex in rats to test the hypothesis that the right hemispheric cortical cholinergic projection system is necessary for shift-hits. Rats were trained on a sustained attention task (SAT) consisting of a random sequence of signal trials and non-signal trials, both requiring a distinct lever response from the subject. Following stable task performance, half of the subjects received right unilateral cholino-selective lesions of the basal forebrain by infusions of the immunotoxin 192 IgG-saporin, while the remaining subjects received sham surgeries. Rats were then familiarized with performing a modified version of SAT which consisted of engineered trial sequences to provide an “aggressive” test of the hypothesis based on the performance of pre-defined trials. In particular, the modified SAT included long strings of non-cued trials that were followed by a cued trial, with lesioned animals expected to miss specifically that latter trial. Conversely, neither hits during long strings of cued trials, nor correct rejections during non-cued trials that followed long strings of consecutive hits were expected to be affected by the lesion. Results indicate that right cholinergic losses selectively impair shift-hits. These findings are consistent with recent results from our optogenetic studies showing that cortical cholinergic transients are necessary and sufficient for the detection of cues (Gritton et al., 2016) and they extend these findings by specifying that in the absence of cortical cholinergic activity, subjects remain arrested in a state of perceptual or intrinsic attention.

Related Products: 192-IgG-SAP (Cat. #IT-01)

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