Quisqualic Acid-Induced Seizures During Development: A Behavioral and EEG Study
Samuel J. Thurber
Department of Neurology, Harvard Medical School, Children's Hospital, Boston, Massachusetts, U.S.A.
Search for more papers by this authorMohamad A. Mikati
Department of Neurology, Harvard Medical School, Children's Hospital, Boston, Massachusetts, U.S.A.
Search for more papers by this authorCarl E. Stafstrom
Department of Neurology, Harvard Medical School, Children's Hospital, Boston, Massachusetts, U.S.A.
Search for more papers by this authorFrancis E. Jensen
Department of Neurology, Harvard Medical School, Children's Hospital, Boston, Massachusetts, U.S.A.
Search for more papers by this authorCorresponding Author
Gregory L. Holmes
Department of Neurology, Harvard Medical School, Children's Hospital, Boston, Massachusetts, U.S.A.
Address correspondence and reprint requests to Dr. G. L. Holmes at Clinical Neurophysiology Laboratory, Children's Hospital, 300 Longwood Ave., Boston, MA 02115, U.S.A.Search for more papers by this authorSamuel J. Thurber
Department of Neurology, Harvard Medical School, Children's Hospital, Boston, Massachusetts, U.S.A.
Search for more papers by this authorMohamad A. Mikati
Department of Neurology, Harvard Medical School, Children's Hospital, Boston, Massachusetts, U.S.A.
Search for more papers by this authorCarl E. Stafstrom
Department of Neurology, Harvard Medical School, Children's Hospital, Boston, Massachusetts, U.S.A.
Search for more papers by this authorFrancis E. Jensen
Department of Neurology, Harvard Medical School, Children's Hospital, Boston, Massachusetts, U.S.A.
Search for more papers by this authorCorresponding Author
Gregory L. Holmes
Department of Neurology, Harvard Medical School, Children's Hospital, Boston, Massachusetts, U.S.A.
Address correspondence and reprint requests to Dr. G. L. Holmes at Clinical Neurophysiology Laboratory, Children's Hospital, 300 Longwood Ave., Boston, MA 02115, U.S.A.Search for more papers by this authorAbstract
Summary: Quisqualic acid (QA) is an excitatory amino acid analogue that binds to the glutamate ionotropic receptor subclass AMPA (a–amino–3 hydroxy-5 methyl-4 isoxazol propionic acid) and metabotropic receptor phos-pholipase C. To study its epileptogenic properties, we administered QA through an intraventricular cannula to 23-, 41-, and 60-day-old rats with recording electrodes implanted in amygdala, hippocampus, and neocortex. The frequency power spectra of the recorded EEG was computed by fast fourier transform (FFT), and coherence between anatomic sites was computed. Seizures occurred in all animals receiving QA. The behavioral manifestations of the seizures varied as a function of age, with younger rats demonstrating rigidity and immobility followed by circling activity and intermittent forelimb clonus and 60-day-old animals exhibiting severe, wild running followed by generalized clonus. Ictal electrical discharges occurred in all animals. Neocortical ictal discharges occurred more prominently in the younger animals, and amygdala ictal discharges were more prominent in the older animals. Marked increases in spectral power occurred during the seizures in all anatomic structures and at all frequencies. Our results demonstrate that the clinical manifestations of QA seizures vary during development; results of the neurophysiologic studies suggested that neocortex may play an important role in genesis of QA seizures in immature brain.
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