Contribution of muscarinic acetylcholine receptors to bottom-up amplification of frontal and parietal cortical responses to rare deviant tones in rats.

We previously reported "true" deviance detection in rat frontal and parietal cortex, reflected in amplified evoked frontal and parietal local field potential (eLFP) responses to rare deviant tones, a likely neural mechanism of bottom-up auditory attention. These amplified cortical responses could not be accounted for by stimulus-specific adaptation (SSA) mechanisms alone, implying that they reflect prediction errors calculated by comparing stored expectations to current stimuli. The cholinergic system is well-known to be involved in attention, but the contributions of different acetylcholine receptor (AChR) types in bottom-up as opposed to top-down attention are not fully understood. To test the role of muscarinic receptors in amplifying the neural response to rare tones, we recorded LFPs from the medio-dorsal frontal and posterior parietal cortices of awake male rats exposed to sequences of frequent standard and rare oddball (deviant) tones and compared eLFPs under 0.75 mg/kg of the muscarinic receptor blocker scopolamine vs vehicle injection. We analyzed the amplitudes of specific eLFP components called N1, P2, N2, P3E (early), and P3L (late) to identify the contribution of muscarinic receptors to the oddball amplification at each peak. Administration of scopolamine was associated with a significant reduction of the rare-tone amplification at the frontal N1 and P2 peaks and the parietal N2 peak. In contrast, the frontal P3L oddball amplification was significantly larger in the scopolamine condition. We also observed a reduction in stimulus-induced gamma power under scopolamine. These results suggest that muscarinic receptors contribute to the cortical prediction error response to rare auditory events.