Staying in the zone: Neuromodulatory brain state and hearing function

Neuromodulatory systems that govern autonomic arousal are thought to be critical to sustaining effortful listening, but detailed circuit mechanisms are largely unknown. To address this, we developed a head-fixed behavioral task in mice to study the roles of motivation and arousal in sustained, auditory, feature-based attention, which we call the sustained attention value (SAV) task. Using two-photon imaging of neuromodulatory sensors or axons and Neuropixel recording of neuronal activity in the auditory system during the SAV task, we apply a range of established and novel behavioral and neural modeling approaches to interpret the data, including survival analysis-based signal detection theory and regression, diffusion-decision modeling, and partially observable Markov decision process modeling. We find that mice partially stabilize their arousal near optimal levels for optimal performance when task utility is high. Unexpectedly, acetylcholine in auditory cortex is linked to task-related movements rather than peri-stimulus attention state as has been predicted by prior models and indirect experimental results. In ongoing work, we are determining the roles of other neuromodulators and patterns of local activity in the auditory cortex in the SAV task. Our results provide a foundation for understanding how neuromodulatory systems contribute to self-regulation of auditory attention, including in brain disorders.