GABAergic transmission in the critical period impacts on the thalamic spatial map and navigation behavior

Abstract

To orient and navigate in the environment, the brain transforms vestibular cues into spatial orientation signals. Determining the role of neurotransmission within the neonatal vestibular nucleus (VN) in the establishment of a spatial map and in path integration is essential to our understanding of how spatial coding is shaped during development. Using whole-cell patch-clamp recording in brainstem slices, we found that most VN neurons of postnatal day (P) 3 - 5 rats exhibited long-term depression of GABAA receptor-mediated evoked-postsynaptic current. At this stage, these currents were excitatory in nature. By P14, long-term depression of these currents, which became inhibitory, was observed in only a small proportion of VN neurons. These results suggest a postnatal period during which plastic feature of GABAergic VN synapses is observed. To further study the role of GABAergic transmission in VN on developing acquisition of spatial recognition, we implanted above the VN of P1 or P14 rats with Elvax slice loaded with GABAA receptor antagonist bicuculline. These pups were allowed to recover and studied at different ages. Derangement of a vestibular-related spatial map in thalamus, an upstream relay of the neural circuitry for balance, was observed in adult rats pre-treated with bicuculline at P1 but not in those pre-treated at P14. When tested with a path integration task at the adult stage, rats pretreated with bicuculline at P1 had significantly prolonged training time and deficiency in behavioral parameters (including searching time, returning time, heading angle, and number of errors in dark/ new location probe tests). Comparable deficits were also observed with selective lesion of vestibular-related subnuclei in the adult thalamus. Rats pretreated at P14 however showed no significant difference in light, dark, and new location probe tests. Taken together, we have demonstrated that a postnatal critical period exists for developmental establishment of a neural circuitry for spatial reference and acquisition of spatial navigation. [Supported by RGC 761711M]