Neonatal excitation-inhibition imbalance introduces long-lasting changes to neuronal recruitment in vestibular circuits for spatial navigation

Abstract

A critical period exists during the first 2 postnatal weeks for development of GABAergic transmission in the rat vestibular nucleus (VN). Perturbation of GABAergic transmission in the VN with bicuculline, a GABAA blocker, during this period abolished efficient spatial navigation behaviour in adults. Post-critical period treatment at P21 had no effect. We hypothesized that the behavioural deficits are the result of long-lasting changes in MVN circuitry. The number of parvalbumin-expressing neurons and perineuronal nets was increased in rats treated with bicuculline at P1 as compared with controls. We further found that there was a decrease in amplitude/frequency of sIPSCs and change in firing pattern of projecting vestibular neurons in adult rats with bicuculline treatment at P1. Since the anterodorsal thalamic nucleus (ADN) integrates vestibular input to generate head direction signal for navigation, we examined neuronal activation in the ADN in these rats after natural vestibular stimulation. It was found that c-fos expression pattern in the ADN of P28 rats after wobble rotation was deranged. Taken together, the data show that neonatal disruption of excitation/inhibition balance in the VN leads to long-lasting derangement of MVN circuitry and its output thereby impacting vestibulo-thalamic neuron recruitment in rats and navigational behaviour. Our findings will inform strategies to promote rewiring of brain circuits for rehabilitation.