Ketamine-Induced Activation of the TeA Region in Mice Correlates with Auditory and Visual Hallucinations

Ketamine, a non-competitive NMDA receptor antagonist, is widely used to model hallucination-like states in both humans and animals, yet the precise neural mechanisms underlying its auditory effects remain unclear. This study investigates how ketamine alters auditory perception by targeting the temporal association cortex (TeA), a higher-order auditory processing region. Using a multi-modal approach combining stereotaxic viral injection, fiber photometry-based calcium imaging, immunofluorescence for c-Fos expression, and behavioral analysis via a two-alternative forced choice (2AFC) task, we examined ketamine's impact on TeA function in C57WT mice. We found that ketamine significantly increased c-Fos expression in TeA, indicating elevated overall neuronal activity. Paradoxically, fiber photometry revealed a concurrent reduction in calcium signal intensity, suggesting impaired signal fidelity and auditory information processing. Behaviorally, ketamine-treated mice exhibited marked deficits in high-frequency sound discrimination, supporting a functional link between TeA dysfunction and auditory perceptual impairment. These results suggest that ketamine disrupts auditory cognition by destabilizing TeA circuit dynamics, offering new insights into the neural basis of hallucinations and laying the groundwork for future circuit-targeted interventions.