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 that NPY can also reduce excitability in the chronically epileptic human brain, we recorded intracellularly from dentate granule cells in hippocampal slices from patients with hippocampal seizure onset. NPY had a potent and long-lasting inhibitory action on perforant path-evoked excitatory responses. In comparison, the group 3 metabotropic glutamate receptor agonist L-2-amino-4-phosphonobutyric acid (L-AP4) evoked a mild and transient decrease. NPY-containing axons were found throughout the hippocampus, and in many epileptic patients were reorganized, particularly in the dentate molecular layer. NPY may therefore play a beneficial role in reducing granule cell excitability in chronically epileptic human tissue, and subsequently limit seizure severity.
Department of Neurosurgery, Yale University Medical School, New Haven, Connecticut 06520, USA.
P R
PR
Patrylo
A N
AN
van den Pol
D D
DD
Spencer
A
A
Williamson
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology*; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000502:physiology; D018891:Dentate Gyrus / Q000187:drug effects / Q000503:physiopathology*; D004558:Electric Stimulation; D004569:Electroencephalography / Q000187:drug effects; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology* / Q000601:surgery; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000503:physiopathology / Q000601:surgery; D006801:Humans; D066298:In Vitro Techniques; D009478:Neuropeptide Y / Q000494:pharmacology* / Q000502:physiology*; D019580:Perforant Pathway / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D000613:Aminobutyrates; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D009478:Neuropeptide Y; D018094:Receptors, Metabotropic Glutamate; D015763:2-Amino-5-phosphonovalerate; C012729:2-amino-4-phosphonobutyric acid