{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T03:22:58Z","timestamp":1772248978775,"version":"3.50.1"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T00:00:00Z","timestamp":1617926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>Children born prematurely suffer from learning disabilities and exhibit reading, speech, and cognitive difficulties, which are associated with an auditory processing disorder. However, it is unknown whether gestational age at delivery and the unnatural auditory environment in neonatal intensive care units (NICU) collectively affect proper auditory development and neuronal circuitry in premature newborns. We morphologically characterized fetal development of the medial superior olivary nucleus (MSO), an area important for binaural hearing and sound localization, in the auditory brainstem of baboon neonates at different gestational ages. Axonal and synaptic structures and the tonotopic differentiation of ion channels in the MSO underwent profound refinements after hearing onset in the uterus. These developmental refinements of the MSO were significantly altered in preterm baboon neonates in the NICU. Thus, the maternal environment in uterus is critical for auditory nervous system development during the last trimester of pregnancy and critically affects the anatomic and functional formation of synapses and neural circuitry in the preterm newborn brain.<\/jats:p>","DOI":"10.3389\/fncel.2021.648562","type":"journal-article","created":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T01:12:58Z","timestamp":1617930778000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Structural Refinement of the Auditory Brainstem Neurons in Baboons During Perinatal Development"],"prefix":"10.3389","volume":"15","author":[{"given":"Eun Jung","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaila","family":"Nip","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia","family":"Blanco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun Hee","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2018-0134","article-title":"Prevalence of autism spectrum disorder in preterm infants: a meta-analysis.","volume":"142","author":"Agrawal","year":"2018","journal-title":"Pediatrics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/pr.2012.184","article-title":"Hyperglycemia increases the risk of death in extremely preterm baboons.","volume":"73","author":"Blanco","year":"2013","journal-title":"Pediatr. Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1113\/jphysiol.2007.137976","article-title":"Development of gerbil medial superior olive: integration of temporally delayed excitation and inhibition at physiological temperature.","volume":"584","author":"Chirila","year":"2007","journal-title":"J. Physiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1002\/cne.902290106","article-title":"Afferent influences on brain stem auditory nuclei of the chicken: time course and specificity of dendritic atrophy following deafferentation.","volume":"229","author":"Deitch","year":"1984","journal-title":"J. Comp. Neurol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/0165-3806(94)90161-9","article-title":"Brainstem auditory evoked response development in preterm and term baboons (Papio hamadryas).","volume":"82","author":"Edwards","year":"1994","journal-title":"Brain Res. Dev. Brain Res."},{"key":"B6","doi-asserted-by":"crossref","DOI":"10.1016\/j.ajog.2006.09.014","article-title":"Trends in neonatal morbidity and mortality for very low birthweight infants.","volume":"196","author":"Fanaroff","year":"2007","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2676","DOI":"10.1152\/jn.00523.2016","article-title":"Physiology and anatomy of neurons in the Medial Superior Olive (MSO) of the mouse.","volume":"116","author":"Fischl","year":"2016","journal-title":"J. Neurophysiol."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2014.00042","article-title":"Coincidence detection in the medial superior olive: mechanistic implications of an analysis of input spiking patterns.","volume":"8","author":"Franken","year":"2014","journal-title":"Front. Neural Circuits"},{"key":"B9","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1007\/s004410051346","article-title":"Development of auditory brainstem circuitry. activity-dependent and activity-independent processes.","volume":"297","author":"Friauf","year":"1999","journal-title":"Cell Tissue Res."},{"key":"B10","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1590\/S2179-64912011000200003","article-title":"[Auditory processing evaluation in children born preterm].","volume":"23","author":"Gallo","year":"2011","journal-title":"J. Soc. Bras. Fonoaudiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/pr.2011.33","article-title":"MR imaging correlates of white-matter pathology in a preterm baboon model.","volume":"71","author":"Griffith","year":"2012","journal-title":"Pediatr. Res."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2014.00116","article-title":"The natural history of sound localization in mammals\u2013a story of neuronal inhibition.","volume":"8","author":"Grothe","year":"2014","journal-title":"Front. Neural Circuits"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2746","DOI":"10.3109\/14767058.2012.718385","article-title":"Brainstem auditory response findings in term neonates in intensive care unit.","volume":"25","author":"Jiang","year":"2012","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1136\/adc.2004.057620","article-title":"Randomised trial of parental support for families with very preterm children: outcome at 5 years.","volume":"90","author":"Johnson","year":"2005","journal-title":"Arch. Dis. Child"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1016\/s0896-6273(00)80643-1","article-title":"Coincidence detection in the auditory system: 50 years after Jeffress.","volume":"21","author":"Joris","year":"1998","journal-title":"Neuron"},{"key":"B16","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1038\/nn810","article-title":"Experience-dependent refinement of inhibitory inputs to auditory coincidence-detector neurons.","volume":"5","author":"Kapfer","year":"2002","journal-title":"Nat. Neurosci."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2013.00003","article-title":"Quantitating the subtleties of microglial morphology with fractal analysis.","volume":"7","author":"Karperien","year":"2013","journal-title":"Front. Cell. Neurosci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"8936","DOI":"10.1523\/jneurosci.1079-11.2011","article-title":"Dynamic interaction of Ih and IK-LVA during trains of synaptic potentials in principal neurons of the medial superior olive.","volume":"31","author":"Khurana","year":"2011","journal-title":"J. Neurosci."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00456","article-title":"Impact of auditory experience on the structural plasticity of the ais in the mouse brainstem throughout the lifespan.","volume":"13","author":"Kim","year":"2019","journal-title":"Front. Cell Neurosci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"11399","DOI":"10.1523\/jneurosci.4734-13.2014","article-title":"Developmental profiles of the intrinsic properties and synaptic function of auditory neurons in preterm and term baboon neonates.","volume":"34","author":"Kim","year":"2014","journal-title":"J. Neurosci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1038\/nature09087","article-title":"Presynaptic activity regulates Na(+) channel distribution at the axon initial segment.","volume":"465","author":"Kuba","year":"2010","journal-title":"Nature"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2015.00035","article-title":"Yes, there is a medial nucleus of the trapezoid body in humans.","volume":"9","author":"Kulesza","year":"2015","journal-title":"Front. Neuroanat."},{"key":"B23","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.brainres.2008.01.009","article-title":"Morphological features of the medial superior olive in autism.","volume":"1200","author":"Kulesza","year":"2008","journal-title":"Brain Res."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2014.00381","article-title":"An acoustic gap between the NICU and womb: a potential risk for compromised neuroplasticity of the auditory system in preterm infants.","volume":"8","author":"Lahav","year":"2014","journal-title":"Front. Neurosci."},{"key":"B25","doi-asserted-by":"crossref","first-page":"e1348","DOI":"10.1542\/peds.2009-2448","article-title":"Unilateral hearing loss is associated with worse speech-language scores in children.","volume":"125","author":"Lieu","year":"2010","journal-title":"Pediatrics"},{"key":"B26","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.ijdevneu.2004.12.008","article-title":"Auditory processing deficits in rats with neonatal hypoxic-ischemic injury.","volume":"23","author":"McClure","year":"2005","journal-title":"Int. J. Dev. Neurosci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1111\/j.1749-6632.2012.06445.x","article-title":"Auditory brain development in premature infants: the importance of early experience.","volume":"1252","author":"McMahon","year":"2012","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"3804","DOI":"10.1002\/cne.23379","article-title":"Development of myelination and cholinergic innervation in the central auditory system of a prosimian primate (Otolemur garnetti).","volume":"521","author":"Miller","year":"2013","journal-title":"J. Comp. Neurol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1177\/00034894021110s502","article-title":"Maturation of human auditory cortex: implications for speech perception.","volume":"189","author":"Moore","year":"2002","journal-title":"Ann. Otol. Rhinol. Laryngol. Suppl."},{"key":"B30","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1080\/14992020701383019","article-title":"The human auditory system: a timeline of development.","volume":"46","author":"Moore","year":"2007","journal-title":"Int. J. Audiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1056\/nejmoa0706475","article-title":"Long-term medical and social consequences of preterm birth.","volume":"359","author":"Moster","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00038","article-title":"Distinct distribution patterns of potassium channel sub-units in somato-dendritic compartments of neurons of the medial superior olive.","volume":"13","author":"Nabel","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"B33","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.neubiorev.2011.11.008","article-title":"Auditory processing in autism spectrum disorder: a review.","volume":"36","author":"O\u2019Connor","year":"2012","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B34","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/apa.12481","article-title":"Impact of the NICU environment on language deprivation in preterm infants.","volume":"103","author":"Rand","year":"2014","journal-title":"Acta Paediatr."},{"key":"B35","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1523\/JNEUROSCI.16-03-00993.1996","article-title":"In vitro analysis of optimal stimuli for phase-locking and time-delayed modulation of firing in avian nucleus laminaris neurons.","volume":"16","author":"Reyes","year":"1996","journal-title":"J. Neurosci."},{"key":"B36","doi-asserted-by":"crossref","first-page":"10567","DOI":"10.1523\/JNEUROSCI.22-24-10567.2002","article-title":"Three-dimensional reconstruction of a calyx of Held and its postsynaptic principal neuron in the medial nucleus of the trapezoid body.","volume":"22","author":"Satzler","year":"2002","journal-title":"J. Neurosci."},{"key":"B37","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis.","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"B38","doi-asserted-by":"crossref","first-page":"7887","DOI":"10.1523\/JNEUROSCI.1016-05.2005","article-title":"Posthearing developmental refinement of temporal processing in principal neurons of the medial superior olive.","volume":"25","author":"Scott","year":"2005","journal-title":"J. Neurosci."},{"key":"B39","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1542\/peds.2004-0221","article-title":"Improved survival rates with increased neurodevelopmental disability for extremely low birth weight infants in the 1990s.","volume":"115","author":"Wilson-Costello","year":"2005","journal-title":"Pediatrics"}],"container-title":["Frontiers in Cellular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2021.648562\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T01:13:08Z","timestamp":1617930788000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2021.648562\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,9]]},"references-count":39,"alternative-id":["10.3389\/fncel.2021.648562"],"URL":"https:\/\/doi.org\/10.3389\/fncel.2021.648562","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.12.23.424228","asserted-by":"object"}]},"ISSN":["1662-5102"],"issn-type":[{"value":"1662-5102","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,9]]},"article-number":"648562"}}