Differential balance of prefrontal synaptic activity in successful versus unsuccessful cognitive aging.
Journal of Neuroscience. 2013-01-23; 33(4): 1344-1356
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1. J Neurosci. 2013 Jan 23;33(4):1344-56. doi: 10.1523/JNEUROSCI.3258-12.2013.
Bories C(1), Husson Z, Guitton MJ, De Koninck Y.
(1)Mental Health Institute of Quebec, Quebec City, QC, Canada G1J 2G3.
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.
PMID: 23345211 [Indexed for MEDLINE]