Acquisition of glutamate receptors in central vestibular synapses is crucial for developmental recognition of spatial orientation

Abstract

Causal links between behavior indicative of spatial recognition and molecular mechanisms of synaptic plasticity have been elusive. Signals about head orientations are transmitted from the inner ear to neurons in the vestibular nucleus. We found that functional maturation of these central neurons occurred after developmental acquisition of specific glutamate receptor subtypes in postsynaptic sites such that functionally silent synapses are converted into functional ones. During this process, long-lasting enhancement of synaptic excitability was expressed. We further demonstrated that perturbation of such glutamate receptor-dependent synaptic efficacy in the vestibular nucleus delayed the developmental emergence of a gravity-triggered orienting behavior in rats. Furthermore, blockade of glutamate receptors in the vestibular nucleus during a postnatal period of susceptibility resulted in a cascade of consequences in mature animals. The establishment of a spatial reference map of 3-dimensional orientations was deterred in the inferior olive. As a consequence, synaptic plasticity in cerebellar Purkinje cells was attenuated and the animals exhibited motor learning deficits. Deficits in spatial navigation ability were also evidenced. Altogether, our findings imply that postnatal expansion of experience is important for maturation of the vestibular circuitry and expression of spatial recognition behaviors. [Supported by HKRGC 761407M, 761409M, 761710M.]