Glutamatergic transmission in the vestibular nucleus is critical to the formation of spatial topography and acquisition of spatial navigation in rats behaviour

Abstract

In the adult, recognition of head orientation is achieved by integration of labyrinthine inputs at multiple levels of the central vestibular circuitry. How these inputs are recruited during postnatal development remains unclear. We hypothesize that topographic maps representing head orientations emerge with maturation of glutamate neurotransmission along the ascending vestibular pathway. Fos expression was used as an indicator to map neurons functionally activated by passive horizontal motions. Each relay station of the pathway (vestibular nucleus, prepositus hypoglossal nucleus, inferior olive, and thalamus) is denotable by a postnatal day (P4, P7, P11, P14) at which neurons became responsive to the stimulus. A topographic organization of neurons responsive to horizontal angular and linear motions also emerged with maturation. Neonatal perturbation of glutamate transmission in the vestibular nucleus was found to derange formation of such spatial representations in both the inferior olive and the thalamus. When tested with a path integration task at the adult stage, rats pretreated with NMDA receptor antagonist MK801 at P2 had prolonged training time and deficiency in behavioral parameters (including searching time, returning time, heading angle, and errors made during dark/new location probe tests). Taken together, we demonstrate that developmental refinement of glutamatergic synapses in the vestibular nucleus plays a crucial role in the establishment of a spatial topography that impacts on spatial navigation in the adult. [Supported by RGC Grants HKU761409, HKU761710, HKU761711]