KNOCK-OUT MICE REVEAL A CRITICAL ANTIEPILEPTIC ROLE FOR NEUROPEPTIDE-Y

Neuropeptide Y (NPY) inhibits excitatory synaptic transmission in the hippocampus and is implicated in control of limbic seizures. In the pr esent study, we examined hippocampal function and the response to phar macologically induced seizures in mutant mice lacking this peptide. In slice electrophysiology studies, no change in normal hippocampal func tion was observed in NPY-deficient mice compared with normal wild-type littermates. Kainic acid (KA) produced limbic seizures at a comparabl e latency and concentration in NPY-deficient mice compared with litter mates. However, KA-induced seizures progressed uncontrollably and ulti mately produced death in 93% of NPY-deficient mice, whereas death was rarely observed in wild-type littermates. Intracerebroventricular NPY infusion, before KA administration, prevented death in NPY-deficient m ice, These results suggest a critical role for endogenous NPY in seizu re control.