Impaired folate metabolism reshapes auditory response profiles and impairs loudness perception in MTHFR-deficient mice.

Folate metabolism, regulated by methylenetetrahydrofolate reductase (MTHFR), is crucial for proper neurodevelopment, and disruptions-whether due to genetic polymorphisms or maternal nutritional deficits-have been linked to cognitive and behavioral impairments. Notably, MTHFR-deficient mouse models display altered social interaction and auditory communication, hinting at disruptions in auditory-related circuits and prompting the question of whether impaired folate metabolism might also affect sound processing and perception. Here, using two-photon calcium imaging, we show that MTHFR deficiency increases both spontaneous and sound-evoked activity in the auditory cortex and significantly shifts neuronal response profiles, which in turn elevates perceived loudness while reducing sound-level discrimination.

Repeated stress gradually impairs auditory processing and perception.

Repetitive stress, a common feature of modern life, is a major risk factor for psychiatric and sensory disorders. Despite the prevalence of perceptual abnormalities in these disorders, little is known about how repetitive stress affects sensory processing and perception. Here, we combine repetitive stress in mice, longitudinal measurement of cortical activity, and auditory-guided behaviors to test if sound processing and perception of neutral sounds in adults are modulated by repetitive stress.