Antidepressant reactivates the plasticity of vestibular-dependent navigation in the adult

Abstract

Antidepressant is known to reactivate the critical period for ocular dominance in adult rats. In the vestibular system, we have previously revealed an early critical period during which neuronal activities in the vestibular nucleus (VN) shaped adult navigation behavior. It is known that one key factor that determines the critical period is the ratio of excitation to inhibition (E/I ratio), which declines from birth to adulthood. We therefore hypothesize that antidepressant can restore the plasticity of navigation behavior by switching E/I ratio of the adult VN to a neonatal state. In the present study, we treated juvenile rats with antidepressant for one week, and found that perturbation of neurotransmission in the VN even after the postnatal critical period could lead to deficits in spatial navigation at adult stage. To determine whether the observed restoration of navigation plasticity is accompanied by an increase in E/I ratio within the VN after antidepressant treatment, we used in vitro whole-cell patch-clamp technique to measure excitatory postsynaptic current (EPSC) and inhibitory postsynaptic current (IPSC) of VN neurons. We found that the E/I ratio was increased to a level comparable to that observed within the postnatal critical period. Notably, a decrease in the frequency of mIPSC but not mEPSC was observed in the VN of juvenile rats treated with antidepressant for one week, suggesting that reduction of inhibitory neurotransmission is the major cause of the increase in E/I ratio. In addition, immunohistochemical results from these juvenile rats revealed a significant increase in the number of proliferating GABAergic VN interneurons following antidepressant treatment. This suggests that antidepressant accelerates neurogenesis of interneurons within the VN. Taken together, our findings suggest that antidepressant restores navigation plasticity in adulthood by increasing E/I ratio in the VN. The mechanism by which antidepressant-induced neurogenesis of interneurons influences the excitation-inhibition balance of the VN circuitry awaits further investigations.