Endocannabinoid (eCB) has been found to mediate retrograde signaling and long-term depression of inhibitory responses (iLTD) in neurons of the amygdala, hippocampus and visual cortex. It remains unexplored whether eCB regulates long-term synaptic plasticity in the vestibular nucleus and behavioral expression of vestibular functions. Whole-cell patch-clamp experiments were performed on brainstem slice of postnatal rats. Theta-burst stimulation delivered to vestibular afferents could induce iLTD of GABAA receptor-mediated evoked-IPSCs in medial vestibular neurons. Such iLTD was induced in 70% of the neurons tested in P5-7 rats but was reduced to 30% in P8-10 rats. In P5-7 rats, the proportion of these neurons was reduced to 30% with bath application of AM251 (antagonist of type 1 cannabinoid receptor). Similar results were obtained in P5-7 rats that had been implanted at P1 with a slice of AM251-loaded Elvax that allowed controlled release of the drug into the underlying vestibular nucleus. In normal P8-10 rats, the proportion was increased to 60% with bath application of WIN55 (agonist of type 1 cannabinoid receptor). Similar results were obtained in P8-10 rats implanted at P1 with WIN55-loaded Elvax slice. To attest the effects of eCB in the expression of vestibular behavior, the Elvax-implanted rats were tested with negative geotaxis, a behavioral indicator of gravity-detection. When compared with normal controls which acquired the re-orienting behavior by P7, emergence of this reflex was accelerated to P5 in AM251-treated rats but was delayed to P11 in WIN55-treated rats. Notably, similar accelerated and delayed emergence of negative geotaxis was observed in rats pretreated with muscimol (a GABAA receptor agonist) and bicuculline (a GABAA receptor antagonist) respectively. 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 responsible for the expression of gravity-detection behavior.
37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, PCB113
Poster Communications: Endocannabinoid modulates developmental plasticity of central vestibular synapses and the expression of vestibular behaviors in rats
W. Shi1, H. Hu1, D. Shum1,2, Y. Chan1
1. Physiology, The University of Hong Kong, Hong Kong, Hong Kong. 2. Biochemistry, The University of Hong Kong, Hong Kong, Hong Kong.
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Where applicable, experiments conform with Society ethical requirements.