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[Preprint]. 2023 Feb 8:2023.02.07.527321. [Version 1] doi: 10.1101/2023.02.07.527321

Neuronal properties of pyramidal cells in lateral prefrontal cortex of the aging rhesus monkey brain are associated with performance deficits on spatial working memory but not executive function

Tara L Moore, Maria Medalla, Sara Ibañez, Klaus Wimmer, Chromewell A Mojica, Ronald J Killiany, Mark B Moss, Jennifer I Luebke, Douglas L Rosene
PMCID: PMC9934587  PMID: 36798388

Abstract

Age-related declines in cognitive abilities occur as early as middle-age in humans and rhesus monkeys. Specifically, performance by aged individuals on tasks of executive function (EF) and working memory (WM) is characterized by greater frequency of errors, shorter memory spans, increased frequency of perseverative responses, impaired use of feedback and reduced speed of processing. However, how aging precisely differentially impacts specific aspects of these cognitive functions and the distinct brain areas mediating cognition are not well understood. The prefrontal cortex (PFC) is known to mediate EF and WM and is an area that shows a vulnerability to age-related alterations in neuronal morphology. In the current study, we show that performance on EF and WM tasks exhibited significant changes with age and these impairments correlate with changes in biophysical properties of L3 pyramidal neurons in lateral LPFC (LPFC). Specifically, there was a significant age-related increase in excitability of Layer 3 LPFC pyramidal neurons, consistent with previous studies. Further, this age-related hyperexcitability of LPFC neurons was significantly correlated with age-related decline on a task of WM, but not an EF task. The current study characterizes age-related performance on tasks of WM and EF and provides insight into the neural substrates that may underlie changes in both WM and EF with age.

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