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While MTHFR polymorphisms have been linked to sensorineural hearing loss and neurodevelopmental disorders in humans, the translation of early-life metabolic stress into long-term sensory processing and perceptual consequences has remained unclear. Here, we combined neonatal ultrasonic vocalization analysis, adult auditory-brainstem recordings, two-photon calcium imaging of the auditory cortex, and high-resolution psychophysics to map the effects of partial Mthfr deficiency across different developmental stages. MTHFR-deficient pups produced calls with lower onset frequencies and altered temporal structure. In adulthood, MTHFR-deficient mice exhibited elevated auditory brainstem response thresholds and reduced wave I amplitudes, indicating reduced cochlear output. Despite robust cortical tone responses, two-photon imaging revealed significantly broadened frequency\u2013response areas, and a trained cortical activity decoder showed selectively reduced separability for closely spaced tones. Guided by these neural findings, behavioral testing revealed intact discrimination for widely separated tones but impaired performance near the perceptual boundary, indicating reduced fine spectral acuity. Together, these findings outline a developmental trajectory in which early metabolic stress impairs peripheral encoding, central gain compensates for the loss of sensitivity, and perceptual precision is ultimately compromised, highlighting one-carbon dysregulation as a modifiable contributor to auditory dysfunction.<\/jats:p>","DOI":"10.1186\/s11689-026-09692-2","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T08:07:02Z","timestamp":1775808422000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Altered folate metabolism disrupts auditory function from neonatal vocalizations to adult perceptual precision"],"prefix":"10.1186","volume":"18","author":[{"given":"Danielle","family":"Barda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lior","family":"Dor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hila","family":"Sapir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaked","family":"Weinberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuval Avni","family":"Mann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aviv","family":"Or-Zeid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Netta","family":"Baram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dror","family":"Lederman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hava","family":"Golan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Resnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"9692_CR1","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/83837","volume":"27","author":"KN Alagramam","year":"2001","unstructured":"Alagramam KN, Murcia CL, Kwon HY, et al. The mouse Ames waltzer hearing-loss mutant is caused by mutation of Pcdh15, a novel protocadherin gene. Nat Genet. 2001;27:99\u2013102.","journal-title":"Nat Genet"},{"key":"9692_CR2","doi-asserted-by":"publisher","first-page":"2468","DOI":"10.1038\/s41467-018-04852-y","volume":"9","author":"MM Asokan","year":"2018","unstructured":"Asokan MM, Williamson RS, Hancock KE, et al. Sensory overamplification in layer 5 auditory corticofugal projection neurons following cochlear nerve synaptic damage. Nat Commun. 2018;9:2468.","journal-title":"Nat Commun"},{"key":"9692_CR3","doi-asserted-by":"publisher","first-page":"e0129934","DOI":"10.1371\/journal.pone.0129934","volume":"10","author":"S Besser","year":"2015","unstructured":"Besser S, Sicker M, Marx G, et al. A transgenic mouse line expressing the red fluorescent protein tdTomato in GABAergic neurons. 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