Cellular abnormalities and synaptic plasticity in seizure disorders of theimmature nervous system

The nervous system has an enhanced capacity to generate seizures during a r estricted phase of postnatal development. Studies in animals and particular ly in in vitro brain slices from hippocampus and neocortex have been instru mental in furthering an understanding of the underlying processes. Developm ental alterations in glutaminergic excitatory synaptic transmission appear to play a key role in the enhanced seizure susceptible of rodents during th e second and third week of life. Prior to this period, the number of excita tory synapses is relatively low. The scarcity of connections and the inabil ity of the existing synapses to release glutamate when activated at high fr equencies likely contribute importantly to the resistance of neonates to se izures. However, at the beginning of week 2, a dramatic outgrowth of excita tory synapses occurs, and these synapses are able to faithfully follow acti vation at high frequencies. These changes, coupled with the prolonged natur e of synaptic potentials in early life, likely contribute to the ease of se izure generation. After this time, seizure susceptibility declines, pattern s of local synaptic connectivity remodel, and some synapses are pruned. Con currently, the duration of excitatory postsynaptic potentials shortens due at least in part to a switch in the subunit composition of postsynaptic rec eptors. Other studies have examined the mechanisms underlying chronic epile psy initiated in early life. Models of both cortical dysplasia and recurren t early-life seizures suggest that alterations in the normal development of excitatory synaptic transmission can contribute importantly to chronic epi leptic conditions. In the recurrent early-life seizure model, abnormal use- dependent selection of subpopulations of excitatory synapses may play a rol e. In experimental cortical dysplasia, alterations in the molecular composi tion of postsynaptic receptor are observed that favor subunit combinations characteristic of infancy. (C) 2000 Wiley-Liss. Inc.