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Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in adults, has a critical contribution to balanced excitatory-inhibitory networks in the brain. Alteration in depolarizing action of GABA during early life is connected to a wide variety of neurodevelopmental disorders. Additionally, the effects of postnatal GABA blockade on neuronal synaptic plasticity are not known and therefore, we set out to determine whether postnatal exposure to bicuculline, a competitive antagonist of GABA A receptors, affects electrophysiologic changes in hippocampal CA1 neurons later on. To this end, male and female Wistar rats received vehicle or bicuculline (300 μg/kg) on postnatal days (PNDs) 7, 9 and 11, and then underwent different behavioral and electrophysiological examinations in adulthood. Postnatal exposure to bicuculline did not affect basic synaptic transmission but led to a pronounced decrease in paired-pulse facilitation (PPF) in CA1 pyramidal neurons. Bicuculline treatment also attenuated the long-term potentiation (LTP) and long-term depression (LTD) of CA1 neurons accompanied by decreased theta-burst responses in male and female adult rats. These electrophysiology findings together with the reduced brain-derived neurotrophic factor (BDNF) levels in the hippocampus and prefrontal cortex reliably explain the disturbance in spatial reference and working memories of bicuculline-treated animals. This study suggests that postnatal GABA A blockade deteriorates short- and long-term synaptic plasticity of hippocampal CA1 neurons and related encoding of spatial memory in adulthood. • Postnatal blockade of GABA A receptor deteriorates the short-term synaptic plasticity and complex response profile of CA1 neurons in adulthood. • Neonatal GABA A blockade attenuates the LTP and LTD in SC–CA1 pathway. • Early life administration of bicuculline results in a deficit in spatial reference and working memories in adult rats. • Postnatal bicuculline decreases the BDNF levels in hippocampus and prefrontal cortex of adult rats. [ABSTRACT FROM AUTHOR]