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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

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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 layer 3 (L3) pyramidal neurons in lateral LPFC (LPFC). Specifically, there was a significant age-related increase in excitability of L3 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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Data Availability

All data were generated at Boston University. Derived data supporting the findings of this study are available from the corresponding author [TLM] on request.

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Acknowledgements

The authors thank Bethany Bowley, Penny Shultz, Karen Slater and Ethan Gaston for their invaluable assistance with this project and the CERCA Program/Generalitat de Catalunya for institutional support.

Funding

This project was funded by: NIH/NIA RF1AG043640, NIH/NIA RF1AG062831, NIH/NIA R01AG078460, NIH/NIA R01AG043478, NIH/NIA P01 AG000001, NIA-NSF CRCNS R01 AG071230, NIH/NIA R01 AG059028, PCI2020-112035 (Spanish State Research Agency (AEI)), the European Union “NextGenerationEU/PRTR”, the Spanish State Research Agency, Severo Ochoa and Maria de Maeztu program for Centers and Units of Excellence in R&D (CEX2020-001084-M).

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Authors and Affiliations

  1. Department of Anatomy & Neurobiology, Boston University Chobanian & Avedisian School of Medicine, 700 Albany Street, W701, MA, 02118, Boston, USA

    Tara L. Moore, Maria Medalla, Chromewell A. Mojica, Ronald J. Killiany, Mark B. Moss, Jennifer I. Luebke & Douglas L. Rosene

  2. Center for Systems Neuroscience, Boston University, MA, 02115, Boston, USA

    Tara L. Moore, Maria Medalla, Ronald J. Killiany, Mark B. Moss, Jennifer I. Luebke & Douglas L. Rosene

  3. Centre de Recerca Matemàtica, Edifici C, Campus Bellaterra, 08193, Bellaterra, Spain

    Sara Ibañez & Klaus Wimmer

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  1. Tara L. Moore
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Correspondence to Tara L. Moore.

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Moore, TL and Medalla, M are co-1st authors.

Luebke JL and Rosene DL are co-senior authors.

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Moore, T.L., Medalla, M., Ibañez, S. et al. 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. GeroScience 45, 1317–1342 (2023). https://doi.org/10.1007/s11357-023-00798-2

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