Conclusion
In conclusion, the neonatal network shifts from one in which GABAa and NMDA receptors dominate and mediate most of the excitatory drive on developing neurons to an adult form in which glutamate mediates excitation through activation of AMPA and NMDA receptors and GABA exerts its well documented inhibitory action. This sequential pattern of development in addition with transient functional over-expression of neurotransmitter will affect seizure thresholds as well as clinical manifestation of the seizures in the developing brain.
In the mammalian CNS, maturation of neuronal network extends into postnatal life, and is often characterized by intense remodeling of connectivity. Initially demonstrated at the neuromuscular junction, remodeling of connectivity within the CNS also appears to be an activity-dependent process. The best-documented example of activity-dependent remodeling in the CNS comes from the study of axonal segregation within the visual system (see 15 for review). Similarly, it has been recently proposed that the appearance of functional postsynaptic AMPA receptors11 or the shortening of NMDA receptor mediated EPSPs18 are also modulated by neuronal synaptic activity. Thus, seizures in the developing brain may likely affect the pattern and/or the timing of appearance of functional synapses. Since learning and behavioral problems are over-represented in children with epilepsy, one of the main challenges in the future will be to determine whether and how synchronized epileptiform discharges can affect the sequential maturation of GABAergic and glutamatergic synaptic transmission, and more generally the brain development.
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Gaiarsa, JL., Ben-Ari, Y. (2001). Ontogenesis of Gabaergic and Glutamatergic Synaptic Transmission. In: Jambaqué, I., Lassonde, M., Dulac, O. (eds) Neuropsychology of Childhood Epilepsy. Advances in Behavioral Biology, vol 50. Springer, Boston, MA. https://doi.org/10.1007/0-306-47612-6_5
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