Glutamatergic synaptic plasticity in medial vestibular nuclei during vestibular compensation

Abstract

Vestibular compensation, the spontaneous recovery from vestibular dysfunction following unilateral vestibular loss, serves as a valuable model for investigating post-lesion plasticity in the adult central nervous system. Elucidating the mechanisms underlying vestibular compensation also offers promising therapeutic avenues for treating vestibular disorders. While most studies have focused on the dynamics of GABAergic synaptic plasticity and intrinsic cellular adaptations in the ipsilesional medial vestibular nucleus (MVN) after unilateral labyrinthectomy (UL), the role of glutamatergic synaptic plasticity in this process remains largely unexplored. Here, we employed Golgi staining, immunofluorescence, whole-cell patch-clamp recordings, and behavioral assessments to examine the structural and functional dynamics of glutamatergic synapses during vestibular compensation. Our results reveal rapid structural and functional plasticity of glutamatergic transmission in response to UL. Specifically, dendritic spine density and morphology in the ipsilesional MVN recovered to baseline levels within 6 to 24 h post-UL. Furthermore, UL-induced postsynaptic depression of glutamatergic synaptic strength, reflected by a reduced AMPA/NMDA ratio, was reversed within 24 h, likely due to an upregulation of Ca²⁺-permeable AMPA receptors. In contrast, presynaptic glutamate release probability, as indicated by a reduced frequency of spontaneous excitatory postsynaptic currents, was not fully compensated during this period. These results suggest that while presynaptic properties recover more slowly in ipsilesional MVN neurons following UL, postsynaptic glutamatergic transmission undergoes rapid structural and functional reorganization. The findings highlight glutamatergic synaptic plasticity as a critical driver for vestibular compensation and suggest that pharmacological interventions targeting these mechanisms may accelerate functional recovery, offering potential therapeutic avenues for vestibular disorders.