Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland, USA
A preferential lesion of neurons in layer III of the entorhinal
cortex (EC) is often observed in patients suffering from temporal
lobe epilepsy and in several animal models of the disease. This
lesion is duplicated in rats by a focal, intra-entorhinal injection
of the "indirect" excitotoxin aminooxyacetic acid (AOAA), providing
a model that can be used to study the mechanisms underlying
seizure-induced cell death and epilepsy. Doomed neurons in the
EC and in several associated limbic structures show pathological
changes within hours after the AOAA injection, but GABAergic
neurons in layer III of the EC are quite resistant. This pattern
of neuron loss eventually results in hippocampal and entorhinal
hyperexcitability. Notably, the seizure-induced death of layer
III neurons in the EC can be attenuated by eliminating the prominent
excitatory input from the presubiculum. Taken together, these
results suggest opportunities to target parahippocampal structures
for the treatment of temporal lobe epilepsy.
