Relationship between age-related cognitive impairment and anatomical changes in dendritic bundles and neuronal microcolumns in the prefrontal cortex

Frank Jones

doi:10.17918/etd-6677

The effects of normal aging in the brain can be characterized by mild impairments in memory and executive function. The earliest of these impairments start developing in healthy people in their mid to late thirties and progress until old age, but the neuroanatomical basis of this cognitive decline is not known. Extensive studies have shown that neurons are not lost in normal aging in contrast with neurodegenerative diseases such as Alzheimer's disease. However, decreases in microcolumnar "strength" correlate with cognitive decline, suggesting that subtle spatial alterations between neurons may impair their function. Previous work has shown that dendritic arbors undergo age-related changes in area 46. One hypothesis is that these changes in dendritic arbors may contribute to micrometer-scale alterations of the surrounding cortical tissue that could ultimately lead to the disruptions in neuron position and microcolumnar strength. We developed a method to identify and measure the width of and spacing between dendrite bundles in Layers 3 and 4 of both banks of the sulcus principalis of 17 behaviorally tested female rhesus monkeys aged 6 to 31 years. There are significant age related changes in dendrite bundle spacing primarily in layer 4 of the ventral bank. Both banks exhibit an increase in the variance of inter-bundle distances with age. These changes may reflect a change in the organization of dendrites within a bundle, or a change in the number of dendrites in the area. Both possibilities could significantly affect the inter-connectivity between microcolumns, layers, and cortices. These measurements were then compared with microcolumn strength and inter-column distance of neuronal microcolumns in both banks of layer 3 of the same animals. While no significant correlation between microcolumn measurements and dendrite bundle measurements is identified, we did observe that the spacing between neuronal microcolumn and dendritic bundles is approximately the same, which is consistent with the view that bundles of apical dendrites form the core of the neuronal microcolumns. During this investigation we became aware of various factors that influence the reported inter-column spacing including: slice thickness, intersection angle of columns with the slice, organization of columns, and the imaging process. To address these factors we propose several modifications to an existing method for identifying neurons in 3 dimensional confocal image stacks and propose an algorithm to identify microcolumns in 3 dimensional reconstructions of tissue from these images. Using this method, we present a sample application to show how accurate measures of inter-column and inter-bundle spacing can be obtained in future work.

Relationship between age-related cognitive impairment and anatomical changes in dendritic bundles and neuronal microcolumns in the prefrontal cortex

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Relationship between age-related cognitive impairment and anatomical changes in dendritic bundles and neuronal microcolumns in the prefrontal cortex

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