Circuit Mechanism of D1/D2 Cells in the Temporal Association Cortex for Auditory Perceptual Decision-Making

The temporal association cortex (TeA) is a higher-order node in the auditory system, involved in processing complex sound and steering behavior. Although dopamine transmission, specifically mediated by D1 and D2 receptors, is well understood to influence decision-making in subcortical structures such as the VTA, its role within the TeA is generally unclear. The goal of the present study was to examine the requirements for D1/D2 receptor-mediated pathways within the TeA for a task of auditory discrimination. We conditioned mice on a task wherein they had to decide depending on frequency in sound. We then utilized a mix of pharmacological intervention with ketamine, in vivo fiber photometry to assess dopamine dynamics, and post-mortem c-Fos immunofluorescence to investigate neural activation. Our results revealed three major findings. First, behavioral analysis showed that ketamine administration severely disrupted the ability of the mice to discriminate as evidenced by a flattening of the psychometric performance curve. Second, immunofluorescence imaging showed that both the TeA and the linked Ventral Tegmental Area (VTA) were strongly activated when the task was performed. Finally, real-time recordings showed that ketamine displaced the temporal profile of dopamine release in the TeA upon the sound stimulus to render a clear, stimulus-locked peak into a flattened and disorganized, multi-peaked profile. All together, these findings demonstrate that the normal functioning of dopamine circuits within the TeA is not merely associated with, but a necessity for, accurate auditory-guided decision-making. Interference with these signals is definitive proof that the coordinated, balanced activity through D1 and D2 receptors within the TeA is a necessity for this process.