Life-span dendritic and spine changes in areas 10 and 18 of human cortex: A quantitative golgi study

Jacobs, Bob; Driscoll, Lori; Schall, Matthew

doi:10.1002/(sici)1096-9861(19971006)386:4<661::aid-cne11>3.0.co;2-n

Cited by 369 publications

(270 citation statements)

References 155 publications

(176 reference statements)

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“…Recently, Jacobs and colleagues revealed systematic differences in the maturation rate of pyramidal cells in different cortical areas (Travis et al, 2005), confirming and extending their initial observations in V2 and gPFC (Jacobs et al, 1997). Moreover, dendritic and spine loss is a common occurrence in aging (Nakamura et al, 1985;Anderson and Rutledge, 1996;Duan et al, 2003).…”

Section: Methodological Considerationsmentioning

confidence: 57%

Specializations of the granular prefrontal cortex of primates: Implications for cognitive processing

et al. 2005

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The biological underpinnings of human intelligence remain enigmatic. There remains the greatest confusion and controversy regarding mechanisms that enable humans to conceptualize, plan, and prioritize, and why they are set apart from other animals in their cognitive abilities. Here we demonstrate that the basic neuronal building block of the cerebral cortex, the pyramidal cell, is characterized by marked differences in structure among primate species. Moreover, comparison of the complexity of neuron structure with the size of the cortical area/region in which the cells are located revealed that trends in the granular prefrontal cortex (gPFC) were dramatically different to those in visual cortex. More specifically, pyramidal cells in the gPFC of humans had a disproportionately high number of spines. As neuron structure determines both its biophysical properties and connectivity, differences in the complexity in dendritic structure observed here endow neurons with different computational abilities. Furthermore, cortical circuits composed of neurons with distinguishable morphologies will likely be characterized by different functional capabilities. We propose that 1. circuitry in V1, V2, and gPFC within any given species differs in its functional capabilities and 2. there are dramatic differences in the functional capabilities of gPFC circuitry in different species, which are central to the different cognitive styles of primates. In particular, the highly branched, spinous neurons in the human gPFC may be a key component of human intelligence.

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Section: Methodological Considerationsmentioning

confidence: 57%

Specializations of the granular prefrontal cortex of primates: Implications for cognitive processing

et al. 2005

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“…This is to be expected, as glucose metabolism is thought to be an indirect measure of the number of synapses in the cortex and levels of synaptophysin have been shown to correlate with glucose metabolism (Rocher et al 2003). Finally, the decrease in synapse density late in adolescence corresponds well with the increasing ability to perform certain prefrontal cortical-dependent tasks (Casey et al 2000), A previous study in the human suggested that supragranular pyramidal neuron spine density, a measure of excitatory synapses, continues to decrease beyond age 20 and does not plateau at the adult level until much later in life, around age 40, at least in prefrontal area 10 and occipital area 18 (Jacobs et al 1997). This would suggest that if we were to continue to examine synaptic marker levels in adults over age 25, their levels would continue to decrease until the plateau corresponding to adult levels is attained.…”

Section: Discussionmentioning

confidence: 91%

Synaptophysin and postsynaptic density protein 95 in the human prefrontal cortex from mid-gestation into early adulthood

Glantz¹,

Gilmore²,

Hamer³

et al. 2007

Neuroscience

234

162

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Previous studies of postnatal synaptic development in human frontal cortex have shown that synaptic density rises after birth, reaches a plateau in childhood and then decreases to adult levels by late adolescence. A similar pattern has been seen in nonhuman primate cortex. These earlier studies in human cortex are limited, however, by significant age gaps in study subjects at critical inflection points of the developmental curve. Additionally, it is unclear if synaptic development occurs in different patterns in different cortical layers in prefrontal cortex (PFC). The purpose of this study was to examine synaptic density in human PFC across development by measuring two synaptic marker proteins: synaptophysin (presynaptic), and postsynaptic density-95 (PSD-95; postsynaptic). Western blotting was used to assess the relative levels of synaptophysin and PSD-95 in dorsolateral PFC of 42 subjects, distributed in age from 18 weeks gestation to 25 years. In addition, synaptophysin immunoreactivity was examined in each layer of areas 9 and 46 of PFC in 24 subjects, ranging in age from 0.1 to 25 years. Synaptophysin levels slowly increased from birth until age 5 and then increased more rapidly to peak in late childhood around age 10. Synaptophysin subsequently decreased until the adult level was reached by mid-adolescence, around age 16. PSD-95 levels increased postnatally to reach a stable plateau by early childhood with a slight reduction in late adolescence and early adulthood. The pattern of synaptophysin immunoreactivity seen with immunohistochemistry was similar to the Western experiments but the changes across age were more subtle, with little change by layer within and across age. The developmental patterns exhibited by these synaptic marker proteins expand upon previous studies of developmental synaptic changes in human frontal cortex; synaptic density increases steadily from birth to late childhood, then decreases in early adolescence to reach adult levels by late adolescence. Keywordsadolescence; development; human; synapses; pruning; synaptogenesisThe human brain has the most protracted period of development of any species, with neurodevelopment continuing well into early adulthood. Imaging studies have shown that in the human, the overall volume of the brain increases during childhood and adolescence (Giedd Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2008 November 9. Sowell et al. 2002;Gilmore et al. 2007). Specifically, the cortical gray matter volume, particularly the f...

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“…While there are higher levels of these proteins in the young, regional decrease in protein levels may reflect synaptic changes, and particularly the loss or dysfunction of dendritic spines occurring in aging [26]. In this regard, synaptic density has been shown to be decreased in the hippocampus from old compared to young subjects [6].…”

Section: Discussionmentioning

confidence: 99%

“…In the current study, we compared the protein expression of cPLA 2 and COX-2 in specific brain regions associated with cognitive function and motor coordination (frontal pole, hippocampus, and cerebellum) in normal healthy Rhesus monkeys at three distinct ages: young (2-5 years), middle aged adult (8-11 years) and old (23 years). Based on the evidence of loss of dendritic spines [26], drebrin [24], and reduced markers for neurotransmission [11,34,46] with aging suggesting synaptic loss, we hypothesize that cPLA 2 and COX-2 protein expression, localized at post-synaptic sites, is decreased in old compared to young monkeys.…”

Section: Introductionmentioning

confidence: 95%

Regional protein levels of cytosolic phospholipase A2 and cyclooxygenase-2 in Rhesus monkey brain as a function of age

Weerasinghe

Coon

Bhattacharjee

et al. 2006

Brain Research Bulletin

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Limited evidence suggests that brain cytosolic phospholipase A 2 (cPLA 2 ), which selectively releases arachidonic acid (AA) from membrane phospholipids, and cyclooxygenase-2 (COX-2), the ratelimiting enzyme for AA metabolism to prostanoids, change as a function of normal aging. In this study, we examined the protein levels of cPLA 2 and COX-2 enzymes in hippocampus, frontal pole and cerebellum from young (2-5 year-old), middle-aged (8-11 year-old) and old (23 year-old) male and female Rhesus monkeys. In the cerebellum, cPLA 2 protein level was higher in the young brain as compared to levels seen at both middle-aged and old. Similarly, in the frontal pole, the young brain showed a higher level of COX-2 protein as compared to the levels seen at both older ages. For both, once an animal reached 8-11 years of age the levels appeared to remain relatively constant over the next decade. Immunohistochemistry of COX-2 protein within the brain demonstrated no significant change in the localization to neurons within the frontal pole. In the young brain, the distribution of a low level of COX-2 protein within numerous neurons was different than the decreased number of neurons stained at a greater intensity in the adult brain. Based on the previous reports of localization of cPLA 2 and COX-2 at post-synaptic sites in neurons results from the current study suggest that the elevated protein levels of the two enzymes seen in the younger brain is related to the greater potential for synaptic plasticity across multiple neurons as a function of age and that cPLA 2 and COX-2 may be considered as post-synaptic markers.

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Life-span dendritic and spine changes in areas 10 and 18 of human cortex: A quantitative golgi study

Cited by 369 publications

References 155 publications

Specializations of the granular prefrontal cortex of primates: Implications for cognitive processing

Specializations of the granular prefrontal cortex of primates: Implications for cognitive processing

Synaptophysin and postsynaptic density protein 95 in the human prefrontal cortex from mid-gestation into early adulthood

Regional protein levels of cytosolic phospholipase A2 and cyclooxygenase-2 in Rhesus monkey brain as a function of age

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