A stereological study of the numbers of neurons and glia in the primary visual cortex across the lifespan of male and female rhesus monkeys

Mild age‐related declines in visual function occur in humans and monkeys, independent of ocular pathology, suggesting involvement of central visual pathways (Spear [1993] Vision Res 33:2589–2609). Although many factors might account for this decline, a loss of neurons in primary visual cortex (V1) could be a contributing factor. Previous studies of neuron numbers in V1 reported stability across age, but were limited in the ages and genders studied and sampled only limited parts of V1 or limited cell types, allowing for the possibility of a subtle loss of neurons. We pursued this question in 26 behaviorally tested adult male and female rhesus monkeys ranging from 7.4 to 31.0 years of age by using design‐based stereology to estimate numbers of NeuN‐labeled neurons and thionin‐stained glia within three laminar zones, supragranular (layers II–IVB), granular (IVC), and infragranular (V–VI), across the entirety of V1. There were no significant differences between males and females on any measures, except for total brain weight (P = 0.0038). There was an average of 416,000,000 neurons in V1, but no effect of age on this total or numbers within any laminar zone. Similarly, there was an average of 184,000,000 glia in V1 (44% of the number of neurons), but no effect of age on this total. However, there was a significant age‐related increase in numbers of glia in the infragranular zone, perhaps reflecting a glial response to pathology in myelinated projection fibers. This study provides further evidence that in normal aging neurons are not lost and hence cannot account for age‐related dysfunction. J. Comp. Neurol. 520:3492–3508, 2012. © 2012 Wiley Periodicals, Inc.

[1]  Division on Earth Guide for the Care and Use of Laboratory Animals , 1996 .

[2]  H. Gundersen,et al.  Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator , 1991, The Anatomical record.

[3]  H. Brody,et al.  Structural Changes in the Aging Nervous System , 1970 .

[4]  R. Killiany,et al.  A non-human primate test of abstraction and set shifting: An automated adaptation of the Wisconsin Card Sorting Test , 2005, Journal of Neuroscience Methods.

[5]  S. Palay,et al.  A review of lamination in Area 17 of the visual cortex ofMacaca, mulatta , 1974, Journal of neurocytology.

[6]  M. Tuszynski,et al.  Memory Impairment in Aged Primates Is Associated with Focal Death of Cortical Neurons and Atrophy of Subcortical Neurons , 2004, The Journal of Neuroscience.

[7]  Paul J. Harrison,et al.  Neuronal density, size and shape in the human anterior cingulate cortex: a comparison of Nissl and NeuN staining , 2004, Brain Research Bulletin.

[8]  R. Killiany,et al.  Patterns of cognitive decline in aged rhesus monkeys , 1997, Behavioural Brain Research.

[9]  Mark J. West,et al.  Regionally specific loss of neurons in the aging human hippocampus , 1993, Neurobiology of Aging.

[10]  E. G. Jones,et al.  Numbers and proportions of GABA-immunoreactive neurons in different areas of monkey cerebral cortex , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[11]  A. Peters,et al.  Aging and the Meynert cells in rhesus monkey primary visual cortex , 1993, The Anatomical record.

[12]  C C Hilgetag,et al.  Quantitative architecture distinguishes prefrontal cortical systems in the rhesus monkey. , 2001, Cerebral cortex.

[13]  Paul D. Coleman,et al.  Neuron numbers and dendritic extent in normal aging and Alzheimer's disease , 1987, Neurobiology of Aging.

[14]  J. Morrison,et al.  Numbers of Meynert and layer IVB cells in area V1: A stereologic analysis in young and aged macaque monkeys , 2000, The Journal of comparative neurology.

[15]  R. Killiany,et al.  Recognition memory span in rhesus monkeys of advanced age , 1997, Neurobiology of Aging.

[16]  J. Lund,et al.  Distribution of GABAergic neurons and axon terminals in the macaque striate cortex , 1987, The Journal of comparative neurology.

[17]  J. Tigges,et al.  Neuronal population of area 4 during the life span of the rhesus monkey , 1990, Neurobiology of Aging.

[18]  A. Peters,et al.  The neuroglial population in the primary visual cortex of the aging rhesus monkey , 2008, Glia.

[19]  K. Schilling,et al.  Characterization of the neuronal marker NeuN as a multiply phosphorylated antigen with discrete subcellular localization , 2005, Journal of neuroscience research.

[20]  G. Leuba,et al.  Changes in volume, surface estimate, three-dimensional shape and total number of neurons of the human primary visual cortex from midgestation until old age , 1994, Anatomy and Embryology.

[21]  B. Pakkenberg,et al.  Neocortical neuron number in humans: Effect of sex and age , 1997, The Journal of comparative neurology.

[22]  B. Pakkenberg,et al.  Neocortical and hippocampal neuron and glial cell numbers in the rhesus monkey , 2007, Anatomical record.

[23]  E. Weibel,et al.  A principle for counting tissue structures on random sections. , 1962, Journal of applied physiology.

[24]  J. Johnson,et al.  Changes in Microanatomy, Neurocytology and Fine Structure with Aging , 1975 .

[25]  A. Peters,et al.  The effects of aging on area 46 of the frontal cortex of the rhesus monkey. , 1994, Cerebral cortex.

[26]  M. Tuszynski,et al.  Conservation of neuron number and size in entorhinal cortex layers II, III, and V/VI of aged primates , 2000, The Journal of comparative neurology.

[27]  J. Morrison,et al.  Life and death of neurons in the aging brain. , 1997, Science.

[28]  D. Purves,et al.  Correlated Size Variations in Human Visual Cortex, Lateral Geniculate Nucleus, and Optic Tract , 1997, The Journal of Neuroscience.

[29]  P. D. Spear,et al.  Neural bases of visual deficits during aging , 1993, Vision Research.

[30]  Peter R. Mouton,et al.  Principles and Practices of Unbiased Stereology: An Introduction for Bioscientists , 2002 .

[31]  T Pietsch,et al.  NeuN: a useful neuronal marker for diagnostic histopathology. , 1996, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[32]  A. Leventhal,et al.  GABA and Its Agonists Improved Visual Cortical Function in Senescent Monkeys , 2003, Science.

[33]  J. Morrison,et al.  Preserved Number of Entorhinal Cortex Layer II Neurons in Aged Macaque Monkeys , 1997, Neurobiology of Aging.

[34]  Richard Hollister,et al.  Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease , 1997, Annals of neurology.

[35]  Claus C. Hilgetag,et al.  Are there ten times more glia than neurons in the brain? , 2009, Brain Structure and Function.

[36]  H J Gundersen,et al.  The efficiency of systematic sampling in stereology and its prediction * , 1987, Journal of microscopy.

[37]  P. Rakić,et al.  Numerical relationship between neurons in the lateral geniculate nucleus and primary visual cortex in macaque monkeys , 1996, Visual Neuroscience.

[38]  John H. R. Maunsell,et al.  The visual field representation in striate cortex of the macaque monkey: Asymmetries, anisotropies, and individual variability , 1984, Vision Research.

[39]  Organization of Extrastriate Visual Areas in the Macaque Monkey , 1981 .

[40]  A. Leventhal,et al.  Degradation of stimulus selectivity of visual cortical cells in senescent rhesus monkeys , 2000, Nature Neuroscience.

[41]  E. Fuchs,et al.  Preservation of hippocampal neuron numbers in aged rhesus monkeys , 2003, Neurobiology of Aging.

[42]  J. Morris,et al.  Profound Loss of Layer II Entorhinal Cortex Neurons Occurs in Very Mild Alzheimer’s Disease , 1996, The Journal of Neuroscience.

[43]  W. H. Dobelle,et al.  The topography and variability of the primary visual cortex in man. , 1974, Journal of neurosurgery.

[44]  Alan Peters,et al.  A further evaluation of the effect of age on striate cortex of the rhesus monkey , 1997, Neurobiology of Aging.

[45]  R. DeTeresa,et al.  Neocortical cell counts in normal human adult aging , 1987, Annals of neurology.

[46]  H BRODY,et al.  Organization of the cerebral cortex. III. A study of aging in the human cerebral cortex , 1955, The Journal of comparative neurology.

[47]  R. Bartus,et al.  Localization of cellular changes within multimodal sensory regions in aged monkey brain: Possible implications for age-related cognitive loss , 1980, Neurobiology of Aging.

[48]  M. Colonnier,et al.  A laminar analysis of the number of neurons, glia, and synapses in the visual cortex (area 17) of adult macaque monkeys , 1982, The Journal of comparative neurology.

[49]  D. Rosene,et al.  A cryoprotection method that facilitates cutting frozen sections of whole monkey brains for histological and histochemical processing without freezing artifact. , 1986, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[50]  H. Haug,et al.  Are Neurons of the Human Cerebral Cortex Really Lost During Aging? A Morphometric Examination , 1985 .

[51]  R. J. Mullen,et al.  NeuN, a neuronal specific nuclear protein in vertebrates. , 1992, Development.

[52]  A. Peters The effects of normal aging on myelin and nerve fibers: A review , 2002, Journal of neurocytology.

[53]  J. Tigges,et al.  Effects of aging on the neurons within area 17 of rhesus monkey cerebral cortex , 1989, The Anatomical record.