Antidepressant Reinstates the Plasticity of Vestibular-mediated Navigation in the Adult

Abstract

Spatial navigation in dark depends on egocentric cues with inputs from the vestibular system. We have previously revealed a critical period for this behavior in first two postnatal weeks during which adult navigation behavior can be shaped by early sensory inputs from the vestibular nucleus (VN). As a 5-HT reuptake inhibitor, fluoxetine is known to restore the plasticity in the adult visual cortex. We hypothesize that fluoxetine also restores the plasticity of VN-dependent spatial navigation. In the present study, we demonstrated that perturbation in the sensory inputs from the VN at P21 could still lead to deficits in adult navigation when the rats were orally administered with fluoxetine during P21-28. Both long-term plasticity and the ratio between excitation and inhibition in the VN were also restored to a neonatal state after fluoxetine treatment. In addition, there was a significant increase in the number of parvalbumin-expressing (PV+) cells in those rats treated with fluoxetine during P21-28. With the application of BrdU, new-born PV+ neurons were then identified in the VN after fluoxetine treatment. Blockade in cell proliferation in the VN rescued the derangement in adult navigation behavior, indicating that PV+-neurogenesis plays an important role in the restoration of plasticity in the spatial navigation. Taken together, our findings provide an insight on the role of fluoxetine in restoring plasticity in the adult sensorimotor system. [Supported by HKU 761812M]