Developmental profile of ionotropic glutamate receptors in spinal vestibular neurons of rats

Abstract

Glutamatergic synapses are the major contributors to excitatory neurotransmission in the adult central vestibular system. The maturation profile of ionotropic glutamate receptor subunits (AMPA and NMDA) in functionally activated neurons in the spinal vestibular nucleus (SpV) of postnatal rats remains unclear. In the present study, two experimental approaches were used to address the role of glutamate receptors in the developing vestibular system. Fos-immunohistochemical experiments were first used to chart the time course of maturation of SpV neurons in the coding of vertical head movements. Conscious Sprague-Dawley rats (P4 to adult) were subjected to sinusoidal linear acceleration along the vertical plane. In control experiments, labyrinthectomized animals subjected to stimulation and normal animals that remained stationary showed only sporadically scattered Fos labeled neurons. Functionally activated Fos-labeled neurons were first identified at P7. About 80% of Fos/NMDA or Fos/AMPA double-labeled neurons were observed in each age group studied. These suggest that both ionotropic glutamate receptors contribute to glutamate neurotransmission in saccule-related SpV neurons of postnatal rats. Whole-cell patch clamp experiments were also used to study the profile of NMDA- and AMPA-mediated currents of SpV neurons in response to electrical stimulation of the vestibular nerve in brainstem slices of P3-9 rats. At P3/P5, the evoked excitatory postsynaptic current (eEPSC) was dominated by NMDA receptor-mediated current, ~70% being the NMDA component and ~20% being the AMPA component. At P7/P9, the NMDA component decreased to ~55% while the AMPA component increased to ~45%. At P9, the linear I-V relationship of AMPA receptor-mediated eEPSC indicated the participation of GluR2 subunits in the receptor channel. Taken together, our findings provide evidence that changes in AMPA and NMDA components within glutamatergic synapses is important to the functional maturation of SpV neurons. Supported by HKRGC