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We recently described a pronounced neuronal loss in layer III of the entorhinal cortex (EC) in patients with intractable temporal lobe epilepsy (Du et al., 1993a). To explore the pathophysiology underlying this distinct neuropathology, we examined the EC in three established rat models of epilepsy using Nissl staining and parvalbumin immunohistochemistry. Adult male rats were either electrically stimulated in the ventral hippocampus for 90 min or injected with kainic acid or lithium/pilocarpine. Animals were observed for behavioral changes for up to 6 hr and were killed 24 hr or 4 weeks after the experimental treatments. At 24 hr, all animals that had exhibited a bout of acute status epilepticus showed a consistent pattern of neuronal loss in the EC in Nissl-stained sections. Neurodegeneration was most pronounced in layer III of the medial Ec at all dorsoventral levels. A few surviving neurons were frequently present in the lesioned area. An identical pattern of nerve cell loss was also seen in the EC of rats killed 4 weeks following the treatments. This lesion was completely prevented by an injection of diazepam and pentobarbital, given 1 hr after kainic acid administration. Immunohistochemistry demonstrated a relative resistance of parvalbumin-positive neurons in layer III of the medial EC. Taken together, these experiments indicate that prolonged seizures cause a preferential neuronal loss in layer III of the medial EC and that this lesion may be related to a pathological elevation of intracellular calcium ion concentrations.

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Neuronal gene expression is known to be modulated by functional activity. This modulation is thought to play a key role in determining the differentiation of developing neurons and regulating the operation of mature neurons. Here we describe a regulation of astroglial gene expression by neuronal activity. We report that intense neuronal activity

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In humans temporal lobe epilepsy (TLE) is characterized by recurrent seizures, neuronal hyperexcitability, and selective loss of certain neuronal populations in the hippocampus. Animal models of the condition indicate that a diminution of inhibition mediated by gamma-aminobutyric acid (GABA) accounts for the altered function, and it has been hypothesized that the diminution arises because GABAergic basket interneurons are "dormant" as a result of their being disconnected from excitatory inputs. In hippocampal slices, inhibitory postsynaptic potentials (IPSPs) were elicited in CA1 pyramidal cells by activation of basket cells; responses from an animal model of TLE were compared to those from control tissue. IPSPs evoked indirectly by activation of terminals that then excited basket cells were reduced in the epileptic tissue, whereas IPSPs evoked by direct activation of basket cells, when excitatory neurotransmission was blocked, were not different from controls. These results provide support for the "dormant basket cell" hypothesis and have implications for the pathophysiology and treatment of human TLE.