Antidepressant reinstates the plasticity in the adult vestibular nucleus

Abstract

Antidepressant fluoxetine is known to restore ocular dominance plasticity in adulthood. We hypothesize that fluoxetine can also reinstate the plasticity in the adult vestibular nucleus (VN), including both behavioral and neuronal plasticity. In previous work, a critical period was revealed before P14 when the sensory inputs from the VN shaped the adult navigation behavior. In the present study, we demonstrated that, with orally administration of fluoxetine during P21-28, perturbation in GABAergic transmission in the VN even at P21 could still lead to deficits in spatial navigation of adults, suggesting the restoration in behavioral plasticity induced by fluoxetine. Then, neuronal plasticity in the VN of young adult rats was investigated after fluoxetine treatment. Using whole-cell patch-clamp, we found that the frequency of miniature inhibitory post-synaptic currents (mIPSCs) was significantly decreased after 7-day treatment of fluoxetine, while the proportion of cells exhibiting long-term depression (LTD) mediated by IPSC was increased. This result indicated a reduction in the inhibitory neurotransmission, causing an increase in the ratio of excitation to inhibition (E/I ratio) in the VN of P28 rats, even to a value that was comparable to that within the critical period. What’s more, fluoxetine accelerated neurogenesis in the VN with a significant increase in the number of BrdU+ neurons, among which a majority also expressed parvalbumin (PV+). Taken together, our findings indicate that fluoxetine is able to restore navigation plasticity in adulthood by modulating neuronal plasticity in the VN of young adult rats, in which the balance between excitation and inhibition is reorganised and the neurogenesis is promoted. [Supported by HKU 761812M]