NPY inhibits glutamatergic excitation in the epileptic human dentate gyrus

Neuropeptide Y (NPY) has been shown to depress hyperexcitable activity that has been acutely induced in the normal rat brain. To test the hypothesis t hat NPY can also reduce excitability in the chronically epileptic human bra in, we recorded intracellularly from dentate granule cells in hippocampal s lices from patients with hippocampal seizure onset. NPY had a potent and lo ng-lasting inhibitory action on perforant path-evoked excitatory responses. In comparison, the group 3 metabotropic glutamate receptor agonist L-2-ami no-3-phosphonobutyric acid (L-AP4) evoked a mild and transient decrease. NP Y-containing axons were found throughout the hippocampus, and in many epile ptic patients were reorganized, particularly in the dentate molecular layer , NPY may therefore play a beneficial role in reducing granule cell excitab ility in chronically epileptic human tissue, and subsequently limit seizure severity.