Role of the Y5 neuropeptide Y receptor in limbic seizures

^*Howard Hughes Medical Institute and Department of Biochemistry, University of Washington, Box 357370, Seattle, WA 98195; and ^†Case Western Reserve University, Pediatric Neurology, MTH 6090, 11100 Euclid Avenue, Cleveland, OH 44106

Contributed by Richard D. Palmiter

Abstract

Neuropeptide Y (NPY) is an inhibitory neuromodulator expressed abundantly in the central nervous system that is suspected of being an endogenous antiepileptic agent that can control propagation of limbic seizures. Electrophysiological and pharmacological data suggest that these actions of NPY are mediated by G protein-coupled NPY Y2 and NPY Y5 receptors. To determine whether the NPY Y5 receptor (Y5R) is required for normal control of limbic seizures, we examined hippocampal function and responsiveness to kainic acid-induced seizures in Y5R-deficient (Y5R−/−) mice. We report that Y5R−/− mice do not exhibit spontaneous seizure-like activity; however, they are more sensitive to kainic acid-induced seizures. Electrophysiological examination of hippocampal slices from mutant mice revealed normal function, but the antiepileptic effects of exogenously applied NPY were absent. These data demonstrate that Y5R has an important role in mediating NPY’s inhibitory actions in the mouse hippocampus and suggest a role for Y5R in the control of limbic seizures.

Footnotes

↵ ‡ Present address: Department of Neurological Surgery, University of California at San Francisco, 153 Parnassus Avenue, San Francisco, CA 94143.
↵ § Present address: Department of Cellular and Molecular Pharmacology, University of California at San Francisco, 153 Parnassus Avenue, San Francisco, CA 94143.
↵ ¶ To whom reprint requests should be addressed. E-mail: palmiter{at}u.washington.edu.
Abbreviations:

NPY,

neuropeptide Y;

Y1R,

Y2R, and Y5R, neuropeptide Y1, Y2, and Y5 receptors, respectively;

Y5R−/− mice,

Y5R-deficient mice;

KA,

kainic acid;

ICV,

intracerebroventricular;

ACSF,

artificial cerebrospinal fluid