THE FUNCTIONAL-ORGANIZATION OF THE HIPPOCAMPAL DENTATE GYRUS AND ITS RELEVANCE TO THE PATHOGENESIS OF TEMPORAL-LOBE EPILEPSY

Temporal lobe seizures are frequently associated with a characteristic pattern of hippocampal pathology (hippocampal sclerosis), as well as pathology in other temporal lobe structures. Despite more than a centu ry of study, the relationship between pathology and epileptogenesis re mains unclear. Endfolium sclerosis, which is characterized by the loss of dentate hilar neurons that are presumed to govern dentate granule cell excitability, is evident whenever hippocampal sclerosis exists an d is the only temporal lobe pathology in some patients. Because prolon ged seizures or head trauma produce endfolium sclerosis and granule ce ll hyperexcitability in experimental animals, hilar neuron loss may be the common pathological denominator and primary network defect underl ying development of a hippocampal seizure ''focus.'' Physiological stu dies suggest that vulnerable hilar messy cells normally excite neurons that mediate granule cell inhibition. Recent anatomical studies indic ate that the axons of messy cells project longitudinally, out of the l amellar plane in which their cell bodies lie. If messy cells in one la mella excite inhibitory neurons in surrounding lamellae, neocortical e xcitation of one segment of the granule cell layer may produce lateral inhibition and limit neocortical excitation to the targeted lamella I n patients who have had status epilepticus, prolonged febrile seizures , head trauma, or encephalitis, loss of dentate messy cells may deaffe rent inhibitory neurons, render them ''dormant,'' and thereby disinhib it an enlarged expanse of the granule cell layer. The selective loss o f neurons that normally govern lateral inhibition in the dentate gyrus may cause functional delamination of the granule cell layer and resul t in synchronous, multilamellar discharges in response to cortical sti muli. Repetitive seizures may ultimately produce the full pattern of h ippocampal and mesial temporal sclerosis by destroying cells within th e seizure circuit that were not injured irreversibly by the initial in sult. Thus, hippocampal pathology may be both the cause and effect of seizures that originate in the temporal lobe.