Neurobiology of seizures and behavioral abnormalities

Abstract

Seizures are both caused by and induce a complex set of neurobiological alterations and adaptations. The animal model of amygdala kindling provides insight into the spatiotemporal evolution of these changes as a function of seizure development and progression. Intracellular, synaptic, and microstructural changes are revealed as related to both the primary pathophysiology of kindled seizure evolution and compensatory secondary, or endogenous anticonvulsant adaptations. At the level of gene expression, the balance of these pathological and adaptive processes (as augmented by exogenous medications) probably determines whether seizures will be manifest or suppressed and could account for aspects of their intermittency. As anxiety and emotion modulation are subserved by many of the same neuroanatomic substrates involved in the evolution of complex partial seizures, particularly those of the medial temporal lobe, it is readily conceptualized how vulnerability to a range of psychiatric disorders could be related to the primary or secondary neurochemical alterations associated with seizure disorders. The discrete and methodologically controlled elucidation of the cascades and spatiotemporal distributions of neurobiological alterations that accompany seizure evolution in the kindling model may help resolve some of the difficulty and complexity of elucidating these biobehavioral relationships in the clinic.