title: Hippocampal excitability is increased in aged mice.
abstract: Aging is known to be associated with a high risk of developing seizure disorders. Currently, the mechanisms underlying this increased seizure susceptibility are not fully understood. Several previous studies have shown a loss of subgroups of GABAergic inhibitory interneurons in the hippocampus of aged rodents, yet the network excitability intrinsic to the aged hippocampus remains to be elucidated. The aim of this study is to examine age-dependent changes of hippocampal network activities in young adult (3-5 months), aging (16-18 months), and aged (24-28 months) mice. We conducted intracranial electroencephalographic (EEG) recordings in free-moving animals and extracellular recordings in hippocampal slices in vitro. EEG recordings revealed frequent spikes in aging and aged mice but only occasionally in young adults. These EEG spikes were suppressed following diazepam administration. Spontaneous field potentials with large amplitudes were frequently observed in hippocampal slices of aged mice but rarely in slices from young adults. These spontaneous field potentials originated from the CA3 area and their generation was dependent upon the excitatory glutamatergic activity. We therefore postulate that hippocampal network excitability is increased in aged mice and that such hyperactivity may be relevant to the increased seizure susceptibility observed in aged subjects.
authors.affiliation: Toronto Western Research Institute, University Health Network, Toronto, Ontario, M5T 2S8, Canada.
authors.forename: Youssef Hanna
authors.initials: YH
authors.lastname: El-Hayek
authors.forename: Chiping
authors.initials: C
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Ye
authors.forename: Justin
authors.initials: J
authors.lastname: Wang
authors.forename: Peter L
authors.initials: PL
authors.lastname: Carlen
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D001703:Biophysics; D058256:Brain Waves / Q000502:physiology*; D003975:Diazepam / Q000494:pharmacology; D004558:Electric Stimulation; D004569:Electroencephalography; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011810:Quinoxalines / Q000494:pharmacology; D014851:Wakefulness
chemical_list: D018691:Excitatory Amino Acid Antagonists; D006993:Hypnotics and Sedatives; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D003975:Diazepam
keywords: Aging; EEG; Epilepsy; Hippocampus; Neural network