Deficiency of neural recognition molecule NB-2 affects the development of glutamatergic auditory pathways from the ventral cochlear nucleus to the superior olivary complex in mouse.
Neural recognition molecule NB-2/contactin 5 is expressed transiently during the first postnatal week in glutamatergic neurons of the central auditory system. Here, we investigated the effect of NB-2 deficiency on the auditory brainstem in mouse. While almost all principal neurons are wrapped with the calyces of Held in the medial nucleus of the trapezoid body (MNTB) in wild type, 8% of principal neurons in NB-2 knockout (KO) mice lack the calyces of Held at postnatal day (P) 6. At P10 and P15, apoptotic principal neurons were detected in NB-2 KO mice, but not in wild type. Apoptotic cells were also increased in the ventral cochlear nucleus (VCN) of NB-2 KO mice, which contains bushy neurons projecting to the MNTB and the lateral superior olive (LSO). At the age of 1 month, the number of principal neurons in the MNTB and of glutamatergic synapses in the LSO was reduced in NB-2 KO mice. Finally, interpeak latencies for auditory brainstem response waves II-III and III-IV were significantly increased in NB-2 KO mice. Together, these findings suggest that NB-2 deficiency causes a deficit in synapse formation and then induces apoptosis in MNTB and VCN neurons, affecting auditory brainstem function.
Toyoshima
Manabu
M
Department of Bioengineering, Nagaoka University of Technology, 1603-1, Kamitomiokamachi, Nagaoka, Niigata 940-2188, Japan.
Sakurai
Kunie
K
Shimazaki
Kuniko
K
Takeda
Yasuo
Y
Shimoda
Yasushi
Y
Watanabe
Kazutada
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis; D001306:Auditory Pathways; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D017626:Cochlear Nucleus / Q000196:embryology*; D005971:Glutamates / Q000378:metabolism*; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology; D009847:Olivary Nucleus / Q000196:embryology*
D000911:Antibodies, Monoclonal; D015816:Cell Adhesion Molecules, Neuronal; D005971:Glutamates; C545358:NB-2 protein, mouse