PLASTICITY | Circuitry Reorganization, Regeneration, and Sprouting

In refractory temporal lobe epilepsy, the hippocampal formation seems pivotal in the development of epileptogenesis. Hippocampal neurons are highly vulnerable to excitotoxicity and hypoxia, and the hippocampus often becomes the source of refractory seizures. Recurrent hippocampal seizures also lead to neuronal loss. As neurons die, there is a deafferentation of their synaptic targets, which in turn appears to trigger a structural reorganization that results in re-enervation of those postsynaptic neurons. Although the initial ‘rationale’ for the rewiring of this circuitry might be viewed as homeostatic, morphological plasticity seems to permanently increase the excitatory nature of the hippocampal circuitry, especially after several repeated seizures. These alterations increase susceptibility to later recurrent seizures – i.e., mechanisms contributing to epileptogenesis.