title: Development of glycinergic innervation to the murine LSO and SPN in the presence and absence of the MNTB.
abstract: Neurons in the superior olivary complex (SOC) integrate excitatory and inhibitory inputs to localize sounds in space. The majority of these inhibitory inputs have been thought to arise within the SOC from the medial nucleus of the trapezoid body (MNTB). However, recent work demonstrates that glycinergic innervation of the SOC persists in Egr2; En1(CKO) mice that lack MNTB neurons, suggesting that there are other sources of this innervation (Jalabi et al., 2013). To study the development of MNTB- and non-MNTB-derived glycinergic SOC innervation, we compared immunostaining patterns of glycine transporter 2 (GlyT2) at several postnatal ages in control and Egr2; En1(CKO) mice. GlyT2 immunostaining was present at birth (P0) in controls and reached adult levels by P7 in the superior paraolivary nucleus (SPN) and by P12 in the lateral superior olive (LSO). In Egr2; En1(CKO) mice, glycinergic innervation of the LSO developed at a similar rate but was delayed by one week in the SPN. Conversely, consistent reductions in the number of GlyT2(+) boutons located on LSO somata were seen at all ages in Egr2; En1(CKO) mice, while these numbers reached control levels in the SPN by adulthood. Dendritic localization of GlyT2+ boutons was unaltered in both the LSO and SPN of adult Egr2; En1(CKO) mice. On the postsynaptic side, adult Egr2; En1(CKO) mice had reduced glycine receptor α1 (GlyRα1) expression in the LSO but normal levels in the SPN. GlyRα2 was not expressed by LSO or SPN neurons in either genotype. These findings contribute important information for understanding the development of MNTB- and non-MNTB-derived glycinergic pathways to the mouse SOC.
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research and Department of Pediatrics, University of Pittsburgh Pittsburgh, PA, USA ; Department of Otolaryngology, University of Pittsburgh Pittsburgh, PA, USA.
authors.forename: Stefanie C
authors.initials: SC
authors.lastname: Altieri
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research and Department of Pediatrics, University of Pittsburgh Pittsburgh, PA, USA.
authors.forename: Tianna
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Pediatrics, Case Western Reserve University Cleveland, OH, USA.
authors.forename: Walid
authors.initials: W
authors.lastname: Jalabi
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research and Department of Pediatrics, University of Pittsburgh Pittsburgh, PA, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Maricich
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D003712:Dendrites / Q000378:metabolism; D051767:Early Growth Response Protein 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005998:Glycine / Q000378:metabolism*; D050487:Glycine Plasma Membrane Transport Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009434:Neural Pathways / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018009:Receptors, Glycine / Q000378:metabolism; D065832:Superior Olivary Complex / Q000166:cytology* / Q000254:growth & development*; D065833:Trapezoid Body / Q000166:cytology* / Q000254:growth & development
chemical_list: D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; C080330:En1 protein, mouse; D050487:Glycine Plasma Membrane Transport Proteins; D018398:Homeodomain Proteins; D008869:Microtubule-Associated Proteins; D018009:Receptors, Glycine; C493270:Slc6a5 protein, mouse; D005998:Glycine
keywords: auditory system; brain development; deafness; hearing; mouse models