Synaptic correlates of increased cognitive vulnerability with aging: Peripheral immune challenge and aging interact to disrupt theta-burst late-phase long-term potentiation in hippocampal area CA1

Timothy R. Chapman, Ruth M. Barrientos, Jared T. Ahrendsen, Steven F. Maier, Susan L. Patterson

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Variability in cognitive functioning increases markedly with age, as does cognitive vulnerability to physiological and psychological challenges. Exploring the basis of this vulnerability may provide important insights into the mechanisms underlying aging-associated cognitive decline. As we have previously reported, the cognitive abilities of aging (24-month-old) F344xBN rats are generally good, but are more vulnerable to the consequences of a peripheral immune challenge (an intraperitoneal injection of live Escherichia coli) than those of their younger (3-month-old) counterparts. Four days after the injection, the aging, but not the young rats show profound memory deficits, specific to the consolidation of hippocampus-dependent memory processes. Here, we have extended these observations, using hippocampal slices to examine for the first time the combined effects of aging and a recent infection on several forms of synaptic plasticity. We have found that the specific deficit in long-lastingmemoryobserved in the aged animals after infection is mirrored by a specific deficit in a form of long-lasting synaptic plasticity. The late-phase long-term potentiation induced in area CA1 using theta-burst stimulation is particularly compromised by the combined effects of aging and infection - a deficit that can be ameliorated by intra-cisterna magna administration of the naturally occurring antiinflammatory cytokine IL-1Ra (interleukin-1 receptor antagonist). These data support the idea that the combination of aging and a negative life event such as an infection might produce selective, early-stage failures of synaptic plasticity in the hippocampus, with corresponding selective deficits in memory.

Original languageEnglish (US)
Pages (from-to)7598-7603
Number of pages6
JournalJournal of Neuroscience
Volume30
Issue number22
DOIs
StatePublished - Jun 2 2010

ASJC Scopus subject areas

  • General Neuroscience

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