Perforant path activation of ectopic granule cells that are born after pilocarpine-induced seizures.
Granule cells in the dentate gyrus are born throughout life, and various stimuli can affect their development in the adult brain. Following seizures, for instance, neurogenesis increases greatly, and some new cells migrate to abnormal (ectopic) locations, such as the hilus. Previous electrophysiological studies of this population have shown that they have intrinsic properties that are similar to normal granule cells, but differ in other characteristics, consistent with abnormal integration into host circuitry. To characterize the response of ectopic hilar granule cells to perforant path stimulation, intracellular recordings were made in hippocampal slices from rats that had pilocarpine-induced status epilepticus and subsequent spontaneous recurrent seizures. Comparisons were made with granule cells located in the granule cell layer of both pilocarpine- and saline-treated animals. In addition, a few ectopic hilar granule cells were sampled from saline-treated rats. Remarkably, hilar granule cells displayed robust responses, even when their dendrites were not present within the molecular layer, where perforant path axons normally terminate. The evoked responses of hilar granule cells were similar in several ways to those of normally positioned granule cells, but there were some differences. For example, there was an unusually long latency to onset of responses evoked in many hilar granule cells, especially those without molecular layer dendrites. Presumably this is due to polysynaptic activation by the perforant path. These results indicate that synaptic reorganization after seizures can lead to robust activation of newly born hilar granule cells by the perforant path, even when their dendrites are not in the terminal field of the perforant path. Additionally, the fact that these cells can be found in normal tissue and develop similar synaptic responses, suggests that seizures, while not necessary for their formation, strongly promote their generation and the development of associated circuits, potentially contributing to a lowered seizure threshold.
Center for Neural Recovery and Rehabilitation Research, Helen Hayes Hospital, New York State Department of Health, Route 9W, West Haverstraw, NY 10993-1195, USA. scharfmanh@helenhayeshosp.org
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Scharfman
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Sollas
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Berger
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JH
Goodman
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Pierce
D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives*; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002828:Choristoma / Q000473:pathology / Q000503:physiopathology*; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D018891:Dentate Gyrus / Q000473:pathology / Q000503:physiopathology*; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009924:Organ Culture Techniques; D019580:Perforant Pathway / Q000502:physiology*; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018721:Muscarinic Agonists; C070614:neurobiotin; D010862:Pilocarpine; D001710:Biotin