Numerous anatomical and physiological changes occur in the dentate gyrus of patients with medial temporal lobe sclerosis, a specific form of temporal lobe epilepsy. Although many of the reported changes are potentially preconvulsive, patients do not seize continuously. We hypothesize that neuromodulatory systems present in the epileptic dentate gyrus may help limit neuronal hyperexcitability and/or hypersynchronization. Three such systems are described in detail, including GABA, zinc, and adenosine. In addition, we briefly discuss several other modulatory systems that have not been studied extensively in the epileptic human hippocampus but that are also well suited to controlling neuronal excitability.
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