Normal aging results in decreased synaptic excitation and increased synaptic inhibition of layer 2/3 pyramidal cells in the monkey prefrontal cortex

Luebke, Jennifer I.; Chang, Yu‐Ming; Moore, Tara; Rosene, Douglas L.

doi:10.1016/j.neuroscience.2004.01.035

Cited by 123 publications

(118 citation statements)

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“…Although these experiments were not performed on the same monkeys that were assessed for synapse loss, the synapse loss in the present report, as well as other studies demonstrating significant spine loss with age (Duan et al, 2003), provides a highly plausible explanation for the finding of significantly reduced synaptic excitation in layers 2/3 of the aged rhesus monkey prefrontal cortex. Luebke et al (2004) demonstrated that, by contrast, the frequency of spontaneous inhibitory PSCs is significantly increased with age, with mean values of 15.4Ϯ1.1 Hz in aged, as compared with 10.2Ϯ1.7 Hz in young neurons (Pϭ0.014). This finding is less consistent with the demonstrated loss of approximately 20% of inhibitory (symmetric) synapses from layers 2/3 shown in the present study.…”

Section: Relationship Between Synaptic Loss and Physiological Responsmentioning

confidence: 98%

“…In a previous study, our group has employed whole cell patch clamp recordings to examine the frequency of spontaneous excitatory glutamatergic and inhibitory GABAergic postsynaptic currents (PSCs) in layer 2/3 pyramidal cells in in vitro slices prepared from young and aged rhesus monkeys (Luebke et al, 2004). Consistent with the present findings of significantly reduced numbers of asymmetric synapses in layers 2/3, the frequency of spontaneous excitatory PSCs was significantly reduced with age, with mean values of 4.2Ϯ0.3 Hz in aged neurons, compared with 7.4Ϯ1.0 Hz in young neurons (Pϭ0.0021).…”

Section: Relationship Between Synaptic Loss and Physiological Responsmentioning

confidence: 99%

“…It is important to determine whether changes in the population of synapses with age can explain the increase in the action potential firing rates of layers 2/3 pyramidal cells in area 46 with age (Chang et al, 2005), as well as the accompanying decrease in synaptic excitation and increase in inhibition shown by these neurons (Luebke et al, 2004).…”

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Synapses are lost during aging in the primate prefrontal cortex

2008

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Abstract-An electron microscopic analysis has been carried out on the effects of age on the numerical density of both excitatory (asymmetric) and inhibitory (symmetric) synapses in the neuropil of layers 2/3 and of layer 5 in area 46 from the frontal cortex of behaviorally tested rhesus monkeys. There is no change in the lengths of synaptic junctions with age or in the percentage distribution of synapses relative to the postsynaptic spines and dendritic shafts. However, in layers 2/3 there is an overall loss of about 30% of synapses from 5 to 30 years of age, and both asymmetric and symmetric synapses are lost at the same rate. In layer 5 the situation is different; the overall loss of synapses is only 20% and this is almost entirely due to a loss of asymmetric synapses, since there is no significant loss of symmetric synapses from this layer with age. When the synapse data are correlated with the overall cognitive impairment shown by the monkeys, it is found that there is a strong correlation between the numerical density of asymmetric synapses in layers 2/3 and cognitive impairment, with a weaker correlation between symmetric synapse loss and cognitive impairment. In layer 5 on the other hand there is no correlation between synapse loss and cognitive impairment. However synapse loss is not the only factor causing cognitive impairment, since in previous studies of area 46 we have found that age-related alteration in myelin in this frontal area also significantly contributes to cognitive decline. The synapse loss is also considered in light of earlier studies, which show that the frequency of spontaneous excitatory synaptic responses is reduced with age in layers 2/3 neurons.

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Section: Relationship Between Synaptic Loss and Physiological Responsmentioning

confidence: 98%

Section: Relationship Between Synaptic Loss and Physiological Responsmentioning

confidence: 99%

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Synapses are lost during aging in the primate prefrontal cortex

2008

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“…Electrophysiological studies have revealed a decrease in the frequency of spontaneous excitatory glutamatergic postsynaptic current (EPSC) and an increase in the spontaneous inhibitory GABAergic postsynaptic current (IPSC) in area 46 layer II/III pyramidal neurons with aging, though neither of these electrophysiological measures correlate with executive function or memory, as measured by CSST scores and CII (Luebke et al 2004). In contrast, area 46 layers II/III pyramidal neurons of aged monkeys have increased action potential firing rates and input resistance, and these measures exhibit a U-shaped relationship with CII, DNMS acquisition (errors to criterion), DNMS delay accuracy, and spatial DRST memory span (Chang et al 2005).…”

Section: Pfc Neuronsmentioning

confidence: 99%

“…Some of these effects are attenuated by hormone replacement therapy in nonhuman primate models of menopause. For example, in aged ovariectomized female monkeys, cyclic estradiol replacement consisting of a single injection every 3 weeks (closely mimicking the natural fluctuations of estrogen in Spontaneous IPSC frequency ↑ Not significant (DNMS, DRST, CII, CSST) Luebke et al 2004 premenopausal monkeys) reverses the age-related impairment in DR and modestly improves DNMS scores (Rapp et al 2003). Estrogen replacement also improves CSST performance in middle-aged ovariectomized monkeys (Voytko et al 2009).…”

Section: Estrogenmentioning

confidence: 99%

Neuronal and morphological bases of cognitive decline in aged rhesus monkeys

Hara

Rapp

Morrison

2011

AGE

114

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Rhesus monkeys provide a valuable model for studying the basis of cognitive aging because they are vulnerable to age-related decline in executive function and memory in a manner similar to humans. Some of the behavioral tasks sensitive to the effects of aging are the delayed response working memory test, recognition memory tests including the delayed nonmatching-to-sample and the delayed recognition span task, and tests of executive function including reversal learning and conceptual set-shifting task. Much effort has been directed toward discovering the neurobiological parameters that are coupled to individual differences in age-related cognitive decline. Area 46 of the dorsolateral prefrontal cortex (dlPFC) has been extensively studied for its critical role in executive function while the hippocampus and related cortical regions have been a major target of research for memory function. Some of the key age-related changes in area 46 include decreases in volume, microcolumn strength, synapse density, and α1-and α2-adrenergic receptor binding densities. All of these measures significantly correlate with cognitive scores. Interestingly, the critical synaptic subtypes associated with cognitive function appear to be different between the dlPFC and the hippocampus. For example, the dendritic spine subtype most critical to task acquisition and vulnerable to aging in area 46 is the thin spine, whereas in the dentate gyrus, the density of AGE (2012) large mushroom spines with perforated synapses correlates with memory performance. This review summarizes age-related changes in anatomical, neuronal, and synaptic parameters within brain areas implicated in cognition and whether these changes are associated with cognitive decline.

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Normal Neurocognitive Aging

Fletcher

Rapp

2012

Handbook of Psychology, Second Edition

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The Neurocognitive Study for the Aging (NEUROAGE) was formally established in 2009 with initial funding by the Cyprus Research Promotion Foundation. It is a longitudinal prospective project with a rolling admission process. NEUROAGE aims to investigate cognitive processes such as memory, concentration, speed of information processing, language abilities and executive skills in a large sample of Cypriots (N > 800) who are native speakers of Greek (including the Cypri-

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Normal aging results in decreased synaptic excitation and increased synaptic inhibition of layer 2/3 pyramidal cells in the monkey prefrontal cortex

Cited by 123 publications

References 39 publications

Synapses are lost during aging in the primate prefrontal cortex

Synapses are lost during aging in the primate prefrontal cortex

Neuronal and morphological bases of cognitive decline in aged rhesus monkeys

Normal Neurocognitive Aging

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