title: Intracellular activities related to in vitro hippocampal sharp waves are altered in CA3 pyramidal neurons of aged mice.
abstract: Pyramidal neurons in the hippocampal CA3 area interconnect intensively via recurrent axonal collaterals, and such CA3-to-CA3 recurrent circuitry plays important roles in the generation of hippocampal network activities. In particular, the CA3 circuitry is able to generate spontaneous sharp waves (SPWs) when examined in vitro. These in vitro SPWs are thought to result from the network activity of GABAergic inhibitory interneurons as SPW-correlating intracellular activities are featured with strong IPSPs in pyramidal neurons and EPSPs or spikes in GABAergic interneurons. In view of accumulating evidence indicating a decrease in subgroups of hippocampal GABAergic interneurons in aged animals, we test the hypothesis that the intracellular activities related to in vitro SPWs are altered in CA3 pyramidal neurons of aged mice. Hippocampal slices were prepared from adult and aged C57 black mice (ages 3-6 and 24-28months respectively). Population and single-cell activities were examined via extracellular and whole-cell patch-clamp recordings. CA3 SPW frequencies were not significantly different between the slices of adult and aged mice but SPW-correlating intracellular activities featured weaker IPSC components in aged CA3 pyramidal neurons compared to adult neurons. It was unlikely that this latter phenomenon was due to general impairments of GABAergic synapses in the aged CA3 circuitry as evoked IPSC responses and pharmacologically isolated IPSCs were observed in aged CA3 pyramidal neurons. In addition, aged CA3 pyramidal neurons displayed more positive resting potentials and had a higher propensity of burst firing than adult neurons. We postulate that alterations of GABAergic network activity may explain the reduced IPCS contributions to in vitro SPWs in aged CA3 pyramidal neurons. Overall, our present observations are supportive of the notion that excitability of hippocampal CA3 circuitry is increased in aged mice.
authors.affiliation: Toronto Western Research Institute, University Health Network, Toronto, Ontario M5T 2S8, Canada; Department of Physiology, Faculty of Medical Science, University of Tarbiat Modares, Tehran, Iran.
authors.forename: H
authors.initials: H
authors.lastname: Moradi-Chameh
authors.affiliation: Toronto Western Research Institute, University Health Network, Toronto, Ontario M5T 2S8, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Peng
authors.affiliation: Toronto Western Research Institute, University Health Network, Toronto, Ontario M5T 2S8, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Wu
authors.affiliation: Toronto Western Research Institute, University Health Network, Toronto, Ontario M5T 2S8, Canada; Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario M5T 2S8, Canada. Electronic address: liangz@uhnres.utoronto.ca.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D008810:Mice, Inbred C57BL; D008839:Microelectrodes; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D046509:Tissue Culture Techniques; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005680:gamma-Aminobutyric Acid
keywords: aging; network; rhythm; subiculum