Neurons in the deep layers of superior colliculus are a requisite component of the neuronal network for seizures during ethanol withdrawal.
Ethanol withdrawal (ETX) in ethanol-dependent animals and humans often results in seizure susceptibility. The deep layers of superior colliculus (DLSC) are proposed to be involved in the neuronal networks of several types of seizures. In rodents, ETX results in susceptibility to audiogenic seizures (AGS), and the DLSC are implicated as a critical component of the seizure network in a genetic form of AGS. Ethanol inhibits NMDA receptors, and the binding at these receptors is increased during ETX in certain brain regions. Therefore, the effect of focal microinjection into DLSC of a competitive NMDA receptor antagonist, DL-2-amino-7-phosphonoheptanoic acid (AP7) on ETX seizures was examined. AP7 (2 and 5 nmol/side) microinjected bilaterally into DLSC suppressed AGS, supporting a critical role of the DLSC in the AGS network during ETX. DLSC neuronal firing changes in behaving rats were subsequently examined, using chronically implanted microwire electrodes. Acoustically-evoked DLSC firing was significantly suppressed during ethanol intoxication and during ETX. However, DLSC neurons began firing tonically 1-2 s before the onset of the wild running behavior of AGS. Acoustically-evoked DLSC firing was suppressed during post-ictal depression with recovery beginning as the righting reflex returned. These data support a requisite role of the DLSC in AGS during ETX. These neuronal firing changes suggest an important role of DLSC neurons in generation of the wild running phase of AGS during ETX, which may be a general pathophysiological mechanism and a critical event in the initiation of wild running, since a similar pattern was seen previously in a genetic form of AGS.
Yang
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Department of Pharmacology, Southern Illinois University School of Medicine, P.O. Box 19629, Springfield, IL 62794-9629, USA.
Long
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Faingold
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D000161:Acoustic Stimulation; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D004567:Electrodes, Implanted; D000431:Ethanol / Q000009:adverse effects*; D008297:Male; D009415:Nerve Net / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010775:Photic Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000503:physiopathology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D019966:Substance-Related Disorders / Q000503:physiopathology; D013477:Superior Colliculi / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*
D002492:Central Nervous System Depressants; D000431:Ethanol