Correcting navigation deficits in the adult by targeting inhibitory gating in central vestibular circuits

Abstract

Activity-dependent plasticity underlies postnatal refinementof sensorimotor circuits for maturation of the relevant functions.Using the central vestibular circuits that inform spatial cognition asa model, we show that early regulation of plasticity in GABAergictransmission is crucial for timely consolidation of such circuits andthe consequent emergence of vestibular-related navigation. Neu-romodulators such as 5-HT and endocannabinoids were shown toparticipate in the regulation of plasticity of GABAergic transmis-sion. Probing the connectivity of inhibitory networks in vestibularnucleus with optogenetics revealed the role of inhibitory circuitsin gating signal output from the vestibular nuclei to higher centresfor spatial cognition.We then asked whether navigation deficits caused by postna-tal perturbations to GABAergic transmission in vestibular circuitscould be corrected in the adult stage by altering inhibitory gatingin the circuit. Activation of adult neurogenesis provided for nec-essary plasticity towards activity-dependent rewiring of vestibularcircuits for resumption of effective navigation.Altogether, we demonstrate the significance of inhibitorygating in vestibular function and provide keys to modify gating inmature adult circuits for behavioral recovery.