title: Age Is Associated with Reduced Sharp-Wave Ripple Frequency and Altered Patterns of Neuronal Variability.
abstract: Spatial and episodic memory performance declines with age, and the neural basis for this decline is not well understood. Sharp-wave ripples are brief (∼70 ms) high-frequency oscillatory events generated in the hippocampus and are associated with the consolidation of spatial memories. Given the connection between ripple oscillations and memory consolidation, we investigated whether the structure of ripple oscillations and ripple-triggered patterns of single-unit activity are altered in aged rats. Local field and single-unit activity surrounding sharp-wave ripple events were examined in the CA1 region of the hippocampus of old (n = 5) and young (n = 6) F344 rats during periods of rest preceding and following performance on a place-dependent eyeblink-conditioning task. Neural responses in aged rats differed from responses in young rats in several ways. First, compared with young rats, the rate of ripple occurrence (ripple density) is reduced in aged rats during postbehavior rest. Second, mean ripple frequency during prebehavior and postbehavior rest is lower in aged animals (aged: 132 Hz; young: 146 Hz). Third, single neurons in aged animals responded more consistently from ripple to ripple. Fourth, variability in interspike intervals was greater in aged rats. Finally, neurons were tuned to a narrower range of phases of the ripple oscillation relative to young animals. Together, these results suggest that the CA1 network in aged animals has a reduced "vocabulary" of available representational states.
  
  
  
  The hippocampus is a structure that is critical for the formation of episodic memories. Sharp-wave ripple events generated in the hippocampus have been implicated in memory consolidation processes critical to memory stabilization. We examine here whether these ripple oscillations are altered over the course of the life span, which could contribute to hippocampus-dependent memory deficits that occur during aging. This experiment used young and aged memory-impaired rats to examine age-related changes in ripple architecture, ripple-triggered spike variance, and spike-phase coherence. We found that there are, indeed, significant changes in characteristics of ripples in older animals that could impact consolidation processes and memory stabilization in the aged brain.
authors.affiliation: Evelyn F. McKnight Brain Institute, University of Arizona, Tucson, Arizona 85724, Division of Neural System, Memory & Aging, University of Arizona, Tucson, Arizona 85724.
authors.forename: Jean-Paul L
authors.initials: JP
authors.lastname: Wiegand
authors.affiliation: Evelyn F. McKnight Brain Institute, University of Arizona, Tucson, Arizona 85724, Division of Neural System, Memory & Aging, University of Arizona, Tucson, Arizona 85724.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Gray
authors.affiliation: Evelyn F. McKnight Brain Institute, University of Arizona, Tucson, Arizona 85724, Division of Neural System, Memory & Aging, University of Arizona, Tucson, Arizona 85724.
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Schimanski
authors.affiliation: Evelyn F. McKnight Brain Institute, University of Arizona, Tucson, Arizona 85724, Division of Neural System, Memory & Aging, University of Arizona, Tucson, Arizona 85724.
authors.forename: Peter
authors.initials: P
authors.lastname: Lipa
authors.affiliation: Evelyn F. McKnight Brain Institute, University of Arizona, Tucson, Arizona 85724, Division of Neural System, Memory & Aging, University of Arizona, Tucson, Arizona 85724, Department of Psychology, University of Arizona, Tucson, Arizona 85721, and Departments of Neurology and Neuroscience, University of Arizona, Tucson, Arizona 85724.
authors.forename: C A
authors.initials: CA
authors.lastname: Barnes
authors.affiliation: Evelyn F. McKnight Brain Institute, University of Arizona, Tucson, Arizona 85724, Division of Neural System, Memory & Aging, University of Arizona, Tucson, Arizona 85724, Department of Psychology, University of Arizona, Tucson, Arizona 85721, and scowen@email.arizona.edu.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Cowen
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001767:Blinking; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D003214:Conditioning, Classical; D005071:Evoked Potentials; D008297:Male; D008568:Memory; D009474:Neurons / Q000145:classification / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D011930:Reaction Time
keywords: Fano factor; consolidation; reactivation; senescence; spike-phase coupling