Anatomic and electrophysiologic evidence for a proconvulsive circuit in the dentate gyrus of reeler mutant mice, an animal model of diffuse cortical malformation.
Although cortical malformations (CMs) are often associated with epilepsy, the underlying mechanisms are unknown. The reeler mouse is a model of CM with enhanced susceptibility to epileptiform activity, including the in vitro dentate gyrus, a region normally resistant to seizures. In this study, field potential recordings in hippocampal slices and the Timm stain were used to examine mossy fiber distribution in the dentate gyrus. In artificial cerebrospinal fluid containing bicuculline, 100% of reeler slices and 0% of control slices had spontaneous and antidromic evoked prolonged negative field potential shifts that were blocked by glutamate receptor antagonists. Sections from reeler mice, but not controls, exhibited a dark band of Timm's stain at the molecular layer/granule cell layer border. These data reveal that mossy fiber distribution is altered in reeler mice and coincides with the presence of an abnormal proconvulsive glutamatergic circuit.
Patrylo
Peter R
PR
Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL 62901, USA. ppatrylo@siumed.edu
Willingham
Amy
A
D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000818:Animals; D004396:Coloring Agents; D018891:Dentate Gyrus / Q000002:abnormalities* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D019599:Mossy Fibers, Hippocampal / Q000002:abnormalities / Q000378:metabolism / Q000648:ultrastructure; D009421:Nervous System Malformations / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009434:Neural Pathways / Q000002:abnormalities* / Q000378:metabolism / Q000503:physiopathology; D009924:Organ Culture Techniques; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics
D004396:Coloring Agents; D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D018698:Glutamic Acid