Postnatal refinement of circuit plasticity for spatial navigation

Abstract

The formation and consolidation of neural networks for a specific function are dependent on maturation of synaptic elements in the circuit. We hypothesize that synaptic efficacy of vestibular neurons undergoes postnatal tuning to sharpen spatial coding for the presentation of relevant behaviors. Whole-cell patch-clamp data from the vestibular nucleus (VN) of neonatal rodents indicated that endocannabinoid, serotonin and orexin could tune the efficacy of GABA transmission. The impact of such neuromodulators on postnatal emergence of vestibular- dependent graviceptive reflex was revealed using specific agonist/antagonist delivered to the neonatal VN; the deficits in spatial cognition so caused lasted well into adulthood. However, similar perturbations in juvenile animals posed no effect. To study whether the observed effects were due to perturbation of GABA circuits, we directly attenuated GABA transmission in the neonatal VN and found similar behavioral deficits. Optogenetic activation of inhibitory VN interneurons in these animals revealed permanent reorganization of inhibitory input to projection neurons. We reason that this underlies derangement of spatial maps in the forebrain of the experimental animals with spatial cognition deficits. Altogether, we show that neuro modulators tune GABA transmission and are instrumental in developmental consolidation of the vestibular circuitry for spatial recognition.