Differential balance of prefrontal synaptic activity in successful versus unsuccessful cognitive aging.
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.
Mental Health Institute of Quebec, Quebec City, QC, Canada G1J 2G3.
Cyril
C
Bories
Zoé
Z
Husson
Matthieu J
MJ
Guitton
Yves
Y
De Koninck
D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000503:physiopathology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D007150:Immunohistochemistry; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D008297:Male; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000503:physiopathology*; D017966:Pyramidal Cells / Q000503:physiopathology*; D051381:Rats; D011916:Rats, Inbred F344; D009435:Synaptic Transmission / Q000502:physiology*