Affiliated with Université Laval & CERVO Research Centre

Differential balance of prefrontal synaptic activity in successful versus unsuccessful cognitive aging.

TitleDifferential balance of prefrontal synaptic activity in successful versus unsuccessful cognitive aging.
Publication TypeJournal Article
Year of Publication2013
AuthorsBories C, Husson Z, Guitton MJ, De Koninck Y
JournalJ Neurosci
Volume33
Issue4
Pagination1344-56
Date Published2013 Jan 23
ISSN1529-2401
KeywordsAging, Animals, Behavior, Animal, Cognition, Cognition Disorders, Excitatory Postsynaptic Potentials, Immunohistochemistry, Inhibitory Postsynaptic Potentials, Male, Patch-Clamp Techniques, Prefrontal Cortex, Pyramidal Cells, Rats, Rats, Inbred F344, Synaptic Transmission
Abstract

Normal aging is associated with a variable decline in cognitive functions. Among these, executive function, decision-making, and working memory are primarily associated with the prefrontal cortex. Although a number of studies have examined the structural substrates of cognitive decline associated with aging within this cortical area, their functional correlates remain poorly understood. To fill this gap, we aimed to identify functional synaptic substrates of age-associated frontal-dependent deficits in layer 2/3 pyramidal neurons of medial prefrontal cortex of 3-, 9-, and ≥ 23-month-old Fischer 344 rats. We combined, in the same animals, novelty recognition and exploratory behavioral tasks with assessment of structural and functional aspects of prefrontal synaptic properties. We found that subsets of aged animals displayed stereotyped exploratory behavior or memory deficits. Despite an age-dependent dendritic spine loss, patch-clamp recording of synaptic activity revealed an increase in miniature EPSC frequency restricted to aged animals with preserved exploratory behavior. In contrast, we found a strong positive relationship between miniature IPSC frequency and the occurrence of both stereotyped exploratory behavior and novelty-related memory deficits. The enhanced miniature inhibitory tone was accompanied by a deficit in activity-driven inhibition, also suggesting an impaired dynamic range for modulation of inhibition in the aged, cognitively impaired animals. Together, our data indicate that differential changes in the balance of inhibitory to excitatory synaptic tone may underlie distinct trajectories in the evolution of cognitive performance during aging.

DOI10.1523/JNEUROSCI.3258-12.2013
Alternate JournalJ. Neurosci.
PubMed ID23345211
Grant ListMOP12942 / / Canadian Institutes of Health Research / Canada
R01 AG020529 / AG / NIA NIH HHS / United States