Age-related alterations to working memory and to pyramidal neurons in the prefrontal cortex of rhesus monkeys begin in early middle-age and are partially ameliorated by dietary curcumin.

Chang, Wayne; Weaver, Christina M.; Medalla, Maria; Moore, Tara; Luebke, Jennifer I.

doi:10.1016/j.neurobiolaging.2021.09.012

Cited by 13 publications

(14 citation statements)

References 82 publications

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“…Following this work, in the present study we examined the relationship between performance on the DRST and CSST and biophysical properties of neurons within LPFC, specifically within area 46. Consistent with previous work, 39,40,57 we have shown here that age-related changes in single-neuron biophysical properties of pyramidal neurons in L3 of LPFC in particular correlate with impaired performance on the DRSTsp, but not CSST. These data suggest a potential dissociation between specific cognitive functions -WM performance may depend more strongly on L3 neurons in LPFC area 46 than performance on the CSST.…”

Section: Age-related Changes In Intrinsic Lpfc Neuron Properties Are ...supporting

confidence: 93%

“…Thus, we employed linear regression and correlation analyses of electrophysiological and cognitive measures. Consistent with our previous findings, 40,57 we found a significant negative linear correlation between DRST spatial span and AP rates in response to +80pA to +280pA current amplitudes (Fig. 7A, I = +80pA, 𝑅 !…”

Section: Lpfc Neuronal Firing Rates and Cognitive Performancesupporting

confidence: 92%

“…6C-F). Consistent with our previous findings 39,40,57 , for this cohort of monkeys, increasing age was significantly correlated with higher AP firing rates in response to 2sec current injections (Fig. 6D: I = +130 pA, fixed effects regression, firing rate = 0.38*age + 4.75, 𝑅 !…”

Section: Age-related Changes In Passive and Active Physiological Prop...supporting

confidence: 92%

“…Consistent with previous electrophysiology and aging studies in LPFC, 39,40,57 this study revealed age-related changes in LPFC pyramidal neuron key biophysical intrinsic and firing properties that contribute to increased excitability with age. Specifically, using linear mixed-effects models with random effects and age as a continuous variable, there was a positive linear relationship between age and membrane input resistance (Rn).…”

Section: Age-related Changes In Passive and Active Physiological Prop...supporting

confidence: 91%

“…5C). However, as we have shown previously 39,40,57 , no significant relationship was found between age and resting potential (Vr, p = 0.26; Fig. 5D) or membrane time constant (tau, p = 0.67; Fig.…”

Section: Age-related Changes In Passive and Active Physiological Prop...supporting

confidence: 57%

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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

Moore¹,

Medalla²,

Ibañez³

et al. 2023

Preprint

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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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Section: Age-related Changes In Intrinsic Lpfc Neuron Properties Are ...supporting

confidence: 93%

Section: Lpfc Neuronal Firing Rates and Cognitive Performancesupporting

confidence: 92%

Section: Age-related Changes In Passive and Active Physiological Prop...supporting

confidence: 92%

Section: Age-related Changes In Passive and Active Physiological Prop...supporting

confidence: 91%

Section: Age-related Changes In Passive and Active Physiological Prop...supporting

confidence: 57%

See 3 more Smart Citations

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

Moore¹,

Medalla²,

Ibañez³

et al. 2023

Preprint

View full text Add to dashboard Cite

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Proteomic features of gray matter layers and superficial white matter of the rhesus monkey neocortex: comparison of prefrontal area 46 and occipital area 17

Castro-Mendoza,

Weaver,

Chang

et al. 2024

Brain Struct Funct

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In this novel large-scale multiplexed immunofluorescence study we comprehensively characterized and compared layer-specific proteomic features within regions of interest of the widely divergent dorsolateral prefrontal cortex (A46) and primary visual cortex (A17) of adult rhesus monkeys. Twenty-eight markers were imaged in rounds of sequential staining, and their spatial distribution precisely quantified within gray matter layers and superficial white matter. Cells were classified as neurons, astrocytes, oligodendrocytes, microglia, or endothelial cells. The distribution of fibers and blood vessels were assessed by quantification of staining intensity across regions of interest. This method revealed multivariate similarities and differences between layers and areas. Protein expression in neurons was the strongest determinant of both laminar and regional differences, whereas protein expression in glia was more important for intra-areal laminar distinctions. Among specific results, we observed a lower glia-to-neuron ratio in A17 than in A46 and the pan-neuronal markers HuD and NeuN were differentially distributed in both brain areas with a lower intensity of NeuN in layers 4 and 5 of A17 compared to A46 and other A17 layers. Astrocytes and oligodendrocytes exhibited distinct marker-specific laminar distributions that differed between regions; notably, there was a high proportion of ALDH1L1-expressing astrocytes and of oligodendrocyte markers in layer 4 of A17. The many nuanced differences in protein expression between layers and regions observed here highlight the need for direct assessment of proteins, in addition to RNA expression, and set the stage for future protein-focused studies of these and other brain regions in normal and pathological conditions.

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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

et al. 2023

View full text Add to dashboard Cite

Age-related alterations to working memory and to pyramidal neurons in the prefrontal cortex of rhesus monkeys begin in early middle-age and are partially ameliorated by dietary curcumin.

Cited by 13 publications

References 82 publications

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

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

Proteomic features of gray matter layers and superficial white matter of the rhesus monkey neocortex: comparison of prefrontal area 46 and occipital area 17

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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