Long-term consequences of early postnatal seizures on hippocampal learning and plasticity

Neural activity influences the patterning of synaptic connections and functional organization of developing sensory and motor systems, but the long-term consequences of intense neural activity such as seizures in the developing hippocampus are not adequately understood. To evaluate the possibility that abnormal neural activity during early development may have long-term functional effects in hippocampal circuitry that plays a role in learning, memory and epilepsy, functional properties of hippocampal circuitry were assessed in adult rats that had experienced seizures induced by kainic acid on specific days during early postnatal development. Although previous studies have suggested that the immature hippocampus is relatively resistant to seizure-induced alterations compared with adults, independent behavioural and physiological experiments demonstrated that seizures evoked by kainic acid during early postnatal development induced a long-term loss of hippocampal plasticity manifesting as reduced capacity for long-term potentiation, reduced susceptibility to kindling, and impaired spatial learning, which was associated with enhanced paired-pulse inhibition in the dentate gyrus. The enhancement of inhibition and loss of plasticity were maximal when the seizures occurred on the first day of life, but were also observed when seizures were induced as late as postnatal day 14, which delimited a period of postnatal susceptibility in the developing rat hippocampus when disruption of normal neural activity by seizures produced consistent effects on a hippocampal-dependent behaviour and several forms of hippocampal plasticity implicated in learning, memory and the development of epilepsy in adulthood.