Developmental expression of tyrosine kinase b in rat vestibular nuclear neurons responding to horizontal and vertical linear accelerations

Abstract

Brain-derived neurotrophic factor (BDNF) is known to be crucial for the development of peripheral vestibular neurons. However, the maturation profile of the BDNF signal transducing receptor, tyrosine kinase B (TrkB) in functionally activated otolith-related vestibular nuclear neurons of postnatal rats remains unexplored. In the present study, conscious Sprague-Dawley rats (P4 to adult) were subjected to sinusoidal linear acceleration along the vertical or horizontal axis. Neuronal activation in response to otolith stimulation was defined by the expression of c-Fos in the vestibular nucleus. Labyrinthectomized controls and normal controls showed only a few sporadically scattered c-fos-expressing neurons. In P4-6 test rats, no Fos-labeled neurons were found in the vestibular nuclei and immunostaining for TrkB was weak. The intensity for TrkB in vestibular nuclear neurons increased with age. From P7 onwards, Fos/TrkB double-labeled neurons responsive to vertical stimulation or horizontal interaural stimulation were detected; from P9 those to horizontal antero-posterior stimulation were also detected. These findings indicate a temporal disparity in the processing of gravity-related spatial orientations in space during development of central otolith neurons. At P9, Fos/TrkB double-labeled neurons responsive to horizontal interaural stimulation or vertical stimulation greatly outnumber those responsive to antero-posterior stimulation. The number of double-labeled neurons increased with age, reaching 80–85% of the total Fos-labeled vestibular nuclear neurons in the adult. Our results suggest that TrkB contributes to the mechanism of maturation in central otolith neurons.