Dentate filter function is altered in a proepileptic fashion during aging.
OBJECTIVE
The elderly have an increased incidence and prevalence for seizure disorders. Further, since up to 50% of these cases have no identifiable antecedent, it has been hypothesized that aging of the central nervous system itself may be epileptogenic. Aged rats, compared to adults, exhibit a greater susceptibility to and severity of seizures associated with hippocampal activation. Whether this aging-related change reflects proconvulsive changes in limbic circuitry is unknown and thus was the focus of this study.


METHODS
Hippocampal slices from adult and aged Fischer 344 rats were examined using electrophysiological techniques. The dentate gyrus was our model region since it is involved with both wet-dog shakes and limbic seizures, and it is affected preferentially with age.


RESULTS
No differences were noted between groups in field potential activity elicited with low frequency stimulation. In contrast, 5-Hz molecular layer stimulation could evoke multiple population spikes in approximately 40% of aged versus 0% of adult slices. Further, recording in CA3 revealed that this stimulation paradigm could elicit multiple spikes in aged, but not adult, slices that frequently evolved into spontaneous epileptiform bursts. This change in the capacity of the dentate to respond to and filter afferent input was associated with an aging-related decrease in the frequency of spontaneous IPSPs and an increased propensity for large amplitude prolonged EPSPs following disinhibition.


CONCLUSIONS
These epileptogenic changes in dentate function and circuitry could contribute to the exacerbated susceptibility for hippocampal seizures in aged rodents, as well as the aging-related decline in spatial learning and memory.
Patrylo
Peter R
PR
Department of Physiology, Southern Illinois University School of Medicine, Carbondale, Illinois 62901, USA. ppatrylo@siumed.edu
Tyagi
Isha
I
Willingham
Amy L
AL
Lee
Sung
S
Williamson
Anne
A
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D018891:Dentate Gyrus / Q000503:physiopathology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004569:Electroencephalography / Q000706:statistics & numerical data; D004827:Epilepsy / Q000175:diagnosis / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D006624:Hippocampus / Q000503:physiopathology*; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D008032:Limbic System / Q000503:physiopathology; D009431:Neural Conduction / Q000502:physiology; D018408:Patch-Clamp Techniques; D019580:Perforant Pathway / Q000503:physiopathology*; D051381:Rats; D011916:Rats, Inbred F344; D012720:Severity of Illness Index