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OBJECTIVE AND METHODS To understand how the capabilities of neural coding of spatial cognition is formed during the development of neural circuitry,the role of the inhibitory neurotransmission within the neonatal vestibular nucleus (VN) in the establishment of a spatial map waits to be studied.RESULTS Using wholecell 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, only a small proportion of VN neurons exhibited long-term depression but these currents became inhibitory.These results indicate a postnatal period during which the efficacy of GABAergic VN synapses is altered.To further assess the role of GABAer-gictransmission in VN on developmental acquisition of spatial recognition, we implanted above the VN of rats with EI-vax slice loaded with GABAA receptor antagonist (bicuculline) at various developmental stages, P1, P8 or P14.These pups were allowed to recover and tested for dead reckoning, a path integration task at the adult stage.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 withbicuculline at P1 but not in the other age groups.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 different probe tests, whereas rats pretreated at P8 showed moderate deficiency in-between the rats pretreated with bicuculline at P1 and P14.Together, these data indicate that inhibitory transmission in neonatal VN determines the expression of spatial navigation at the adult stage.CONCLUSION Based on these findings, we conclude that there is a postnatal critical period for developmental establishment of a neural circuitry for spatial reference and acquisition of spatial navigation.