Endocannabinoid regulates developmental plasticity of GABAergic synapses in the rat medial vestibular nucleus

Abstract

Long-term depression of inhibitory responses (iLTD), mediated via retrograde signaling of endocannabinoid (eCB), have been reported in the amygdala, hippocampus and visual cortex. The role of eCB on presynaptic plasticity in the vestibular nucleus which plays a key role in spatial recognition remains unexplored. Immunoreactivity of eCB receptor was observed in the vestibular nucleus of postnatal rats. Whole-cell patch-clamp experiments were also performed on brainstem slice preparations of these animals. Theta-burst stimulation delivered to vestibular afferents could induce iLTD of GABAA receptor-mediated evoked-IPSCs in medial vestibular neurons. In P5-7 rats, iLTD was induced in 80% of the neurons tested. Application of AM251 (antagonist of type 1 cannabinoid receptor) decreased the percentage to 30%. In P8-10 rats, however, the percentage of neurons in which iLTD could be induced was found to be 30%. Treatment with WIN55 (agonist of type 1 cannabinoid receptor) increased the percentage to 70%. Our results therefore indicate that eCB plays an age-dependent role in modulating the efficacy of GABAergic synapses in the vestibular nucleus, thereby regulating activities of neural network within the central vestibular system.