Timely insertion of AMPA receptor in developing vestibular circuits is required for manifestation of righting reflexes and effective navigation.

Vestibular information processed first by the brainstem vestibular nucleus (VN), and further by cerebellum and thalamus, underlies diverse brain function. These include the righting reflexes and spatial cognitive behaviour. While the cerebellar and thalamic circuits that decode vestibular information are known, the importance of VN neurons and the temporal requirements for their maturation that allow developmental consolidation of the aforementioned circuits remains unclear. We show that timely unsilencing of glutamatergic circuits in the VN by NMDA receptor-mediated insertion of AMPAR receptor type 1 (GluA1) subunits is critical for maturation of VN and successful consolidation of higher circuits that process vestibular information. Delayed unsilencing of NMDA receptor-only synapses of neonatal VN neurons permanently decreased their functional connectivity with inferior olive circuits. This was accompanied by delayed pruning of the inferior olive inputs to Purkinje cells and permanent reduction in their plasticity. These derangements led to deficits in associated vestibular righting reflexes and motor co-ordination during voluntary movement. Vestibular-dependent recruitment of thalamic neurons was similarly reduced, resulting in permanently decreased efficiency of spatial navigation. The findings thus show that well-choreographed maturation of the nascent vestibular circuitry is prerequisite for functional integration of vestibular signals into ascending pathways for diverse vestibular-related behaviours.

Maturation of canal-related brainstem neurons in the detection of horizontal angular acceleration in rats.

We examined the functional maturation of canal-related brainstem neurons in Sprague-Dawley rats at postnatal day (P)1 to adult. Conscious animals were subjected to cycles of angular acceleration and deceleration so as to selectively activate hair cells of the horizontal semicircular canals. Brainstem neurons were monitored for c-fos expression by immuno-hybridization histochemistry as an indicator of neuronal activation. Fos-immunoreactive canal-related neurons were identifiable from P4 onwards in the vestibular nucleus and downstream vestibular relay stations, prepositus hypoglossal nucleus, and inferior olive. In the vestibular nucleus and prepositus hypoglossal nucleus, the number of canal-related neurons increased progressively with age, reaching the adult level by P21. Those in the inferior olive increased in number from P4 to P14 but decreased significantly afterwards until adulthood. The topography was not clear in the vestibular nucleus and prepositus hypoglossal nucleus. Canal-related neurons in P4-7 rats were spread throughout the rostrocaudal length of each subnucleus but clusters of canal-related neurons tended to form within specific subnuclei by P21. These were concentrated in the caudal halves of medial and spinal vestibular nuclei and the rostral parts of superior vestibular nucleus and prepositus hypoglossal nucleus. In the inferior olive, the topography was evident early in the course of development. Canal-related neurons were exclusively located in four subnuclei: dorsal medial cell column, dorsal cap, subnucleus A, and subnucleus C, but not in other subnuclei. Taken together, our data revealed the developmental profile of neuronal subpopulations within the horizontal canal system, thus providing an internal neural representation for postnatal coding of horizontal head rotations in spatial perception.