Repetitive stress disrupts auditory cortical processing through changes in circuit and neuromodulatory dynamics

Repetitive stress, a hallmark of modern life, is strongly linked to psychiatric and sensory disorders, yet its direct impact on sensory circuits remains unclear. In this talk, I will present new evidence that chronic stress simultaneously reshapes auditory cortical activity and norepinephrine signaling, producing measurable perceptual consequences in adult mice. Using complementary approaches—repeated-stress paradigms, longitudinal two-photon imaging of neuronal activity and NE dynamics, and auditory-guided behavior—we found that stress boosts spontaneous firing in auditory cortex but dampens sound-evoked responses in pyramidal cells and parvalbumin interneurons. By contrast, somatostatin interneurons become more responsive to sound, a shift that likely suppresses pyramidal and PV activity through enhanced inhibition. These circuit-level changes were accompanied by perceptual alterations, most notably a reduction in loudness perception. Together, our findings reveal a key mechanism for stress-induced sensory plasticity and point to how dysregulated internal states could drive the perceptual anomalies often observed in psychiatric disease.