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The effects of lifelong blindness on murine neuroanatomy and gene expression.

Abbott CW, Kozanian OO, Huffman KJ - Front Aging Neurosci (2015)

Bottom Line: Expression patterns of Ephrin A5, COUP-TFI, and RZRβ and patterns of intraneocortical connectivity (INC) are altered in the neocortices of aging blind mice.Sensory inputs from different modalities during development likely play a major role in the development of cortical areal and thalamic nuclear boundaries.We suggest that early patterning by prenatal retinal activity combined with persistent gene expression within the thalamus and cortex is sufficient to establish and preserve a small but present LGN and V1 into late adulthood.

View Article: PubMed Central - PubMed

Affiliation: Interdisciplinary Neuroscience Graduate Program, University of California, Riverside Riverside, CA, USA.

ABSTRACT
Mammalian neocortical development is regulated by neural patterning mechanisms, with distinct sensory and motor areas arising through the process of arealization. This development occurs alongside developing central or peripheral sensory systems. Specifically, the parcellation of neocortex into specific areas of distinct cytoarchitecture, connectivity and function during development is reliant upon both cortically intrinsic mechanisms, such as gene expression, and extrinsic processes, such as input from the sensory receptors. This developmental program shifts from patterning to maintenance as the animal ages and is believed to be active throughout life, where the brain's organization is stable yet plastic. In this study, we characterize the long-term effects of early removal of visual input via bilateral enucleation at birth. To understand the long-term effects of early blindness we conducted anatomical and molecular assays 18 months after enucleation, near the end of lifespan in the mouse. Bilateral enucleation early in life leads to long-term, stable size reductions of the thalamic lateral geniculate nucleus (LGN) and the primary visual cortex (V1) alongside a increase in individual whisker barrel size. Neocortical gene expression in the aging brain has not been previously identified; we document cortical expression of multiple regionalization genes. Expression patterns of Ephrin A5, COUP-TFI, and RZRβ and patterns of intraneocortical connectivity (INC) are altered in the neocortices of aging blind mice. Sensory inputs from different modalities during development likely play a major role in the development of cortical areal and thalamic nuclear boundaries. We suggest that early patterning by prenatal retinal activity combined with persistent gene expression within the thalamus and cortex is sufficient to establish and preserve a small but present LGN and V1 into late adulthood.

No MeSH data available.


Related in: MedlinePlus

Reduced dLGN and V1 18 months post newborn bilateral enucleation. Cytochrome oxidase staining was used to reveal dLGN architecture and mark primary visual cortex in 18 month control and bilaterally enucleated brains. (A,B): Panels are high magnification views of the dLGN (arrows) and surrounding areas of the dorsal thalamus after sectioning at 40 μm in the coronal plane. CO staining indicates that visual thalamic nuclei (dLGN) are present, but reduced in enucleated brains (B) as compared to controls (A). (C): The dLGN size in enucleated brains is significantly reduced (73.13 ± 5.192%) compared to control brains. (D,E): Panels show hemisected brains sectioned at 40 μm in the coronal plane. A reduction, but not elimination of primary visual cortex (arrows), is observed in enucleated tissue compared to that of controls. (F): V1 size in enucleated cortex is significantly reduced (76.35 ± 1.850%) compared to controls. Tissue oriented with dorsal up and lateral to the right. dLGN Scale bar = 500 μm. dLGN: dorsal lateral geniculate nucleus. **P < 0.01; ***P < 0.001. V1 Scale bar = 500 μm. N = 5 per condition.
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Figure 2: Reduced dLGN and V1 18 months post newborn bilateral enucleation. Cytochrome oxidase staining was used to reveal dLGN architecture and mark primary visual cortex in 18 month control and bilaterally enucleated brains. (A,B): Panels are high magnification views of the dLGN (arrows) and surrounding areas of the dorsal thalamus after sectioning at 40 μm in the coronal plane. CO staining indicates that visual thalamic nuclei (dLGN) are present, but reduced in enucleated brains (B) as compared to controls (A). (C): The dLGN size in enucleated brains is significantly reduced (73.13 ± 5.192%) compared to control brains. (D,E): Panels show hemisected brains sectioned at 40 μm in the coronal plane. A reduction, but not elimination of primary visual cortex (arrows), is observed in enucleated tissue compared to that of controls. (F): V1 size in enucleated cortex is significantly reduced (76.35 ± 1.850%) compared to controls. Tissue oriented with dorsal up and lateral to the right. dLGN Scale bar = 500 μm. dLGN: dorsal lateral geniculate nucleus. **P < 0.01; ***P < 0.001. V1 Scale bar = 500 μm. N = 5 per condition.

Mentions: Initial work for this study began with an investigation of the effects of early bilateral enucleation on the long-term maintenance of the dLGN using CO staining techniques (Figures 2A,B; arrows). Elderly, 18 month old enucleated mice display a significant reduction in dLGN when compared to control animals (Figure 2C, 26.87 ± 5.192% reduction from control; N = 5, P < 0.01) without a change in cell packing density (Figure 3A: control 117.6 ± 3.206; enucleated 109.5 ± 4.065; P > 0.05). These results extend our previous finding of a reduction in dLGN size by P10 (Dye et al., 2012) by demonstrating that the small size of the dLGN is maintained throughout life. Examination of the genes Ephrin A5, Cad8, COUP-TF1, Lhx2 and RZRβ at this elderly time-point revealed no appreciable expression in the dLGN, vLGN or VP in either the control or enucleated cases (data not shown).


The effects of lifelong blindness on murine neuroanatomy and gene expression.

Abbott CW, Kozanian OO, Huffman KJ - Front Aging Neurosci (2015)

Reduced dLGN and V1 18 months post newborn bilateral enucleation. Cytochrome oxidase staining was used to reveal dLGN architecture and mark primary visual cortex in 18 month control and bilaterally enucleated brains. (A,B): Panels are high magnification views of the dLGN (arrows) and surrounding areas of the dorsal thalamus after sectioning at 40 μm in the coronal plane. CO staining indicates that visual thalamic nuclei (dLGN) are present, but reduced in enucleated brains (B) as compared to controls (A). (C): The dLGN size in enucleated brains is significantly reduced (73.13 ± 5.192%) compared to control brains. (D,E): Panels show hemisected brains sectioned at 40 μm in the coronal plane. A reduction, but not elimination of primary visual cortex (arrows), is observed in enucleated tissue compared to that of controls. (F): V1 size in enucleated cortex is significantly reduced (76.35 ± 1.850%) compared to controls. Tissue oriented with dorsal up and lateral to the right. dLGN Scale bar = 500 μm. dLGN: dorsal lateral geniculate nucleus. **P < 0.01; ***P < 0.001. V1 Scale bar = 500 μm. N = 5 per condition.
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Related In: Results  -  Collection

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Figure 2: Reduced dLGN and V1 18 months post newborn bilateral enucleation. Cytochrome oxidase staining was used to reveal dLGN architecture and mark primary visual cortex in 18 month control and bilaterally enucleated brains. (A,B): Panels are high magnification views of the dLGN (arrows) and surrounding areas of the dorsal thalamus after sectioning at 40 μm in the coronal plane. CO staining indicates that visual thalamic nuclei (dLGN) are present, but reduced in enucleated brains (B) as compared to controls (A). (C): The dLGN size in enucleated brains is significantly reduced (73.13 ± 5.192%) compared to control brains. (D,E): Panels show hemisected brains sectioned at 40 μm in the coronal plane. A reduction, but not elimination of primary visual cortex (arrows), is observed in enucleated tissue compared to that of controls. (F): V1 size in enucleated cortex is significantly reduced (76.35 ± 1.850%) compared to controls. Tissue oriented with dorsal up and lateral to the right. dLGN Scale bar = 500 μm. dLGN: dorsal lateral geniculate nucleus. **P < 0.01; ***P < 0.001. V1 Scale bar = 500 μm. N = 5 per condition.
Mentions: Initial work for this study began with an investigation of the effects of early bilateral enucleation on the long-term maintenance of the dLGN using CO staining techniques (Figures 2A,B; arrows). Elderly, 18 month old enucleated mice display a significant reduction in dLGN when compared to control animals (Figure 2C, 26.87 ± 5.192% reduction from control; N = 5, P < 0.01) without a change in cell packing density (Figure 3A: control 117.6 ± 3.206; enucleated 109.5 ± 4.065; P > 0.05). These results extend our previous finding of a reduction in dLGN size by P10 (Dye et al., 2012) by demonstrating that the small size of the dLGN is maintained throughout life. Examination of the genes Ephrin A5, Cad8, COUP-TF1, Lhx2 and RZRβ at this elderly time-point revealed no appreciable expression in the dLGN, vLGN or VP in either the control or enucleated cases (data not shown).

Bottom Line: Expression patterns of Ephrin A5, COUP-TFI, and RZRβ and patterns of intraneocortical connectivity (INC) are altered in the neocortices of aging blind mice.Sensory inputs from different modalities during development likely play a major role in the development of cortical areal and thalamic nuclear boundaries.We suggest that early patterning by prenatal retinal activity combined with persistent gene expression within the thalamus and cortex is sufficient to establish and preserve a small but present LGN and V1 into late adulthood.

View Article: PubMed Central - PubMed

Affiliation: Interdisciplinary Neuroscience Graduate Program, University of California, Riverside Riverside, CA, USA.

ABSTRACT
Mammalian neocortical development is regulated by neural patterning mechanisms, with distinct sensory and motor areas arising through the process of arealization. This development occurs alongside developing central or peripheral sensory systems. Specifically, the parcellation of neocortex into specific areas of distinct cytoarchitecture, connectivity and function during development is reliant upon both cortically intrinsic mechanisms, such as gene expression, and extrinsic processes, such as input from the sensory receptors. This developmental program shifts from patterning to maintenance as the animal ages and is believed to be active throughout life, where the brain's organization is stable yet plastic. In this study, we characterize the long-term effects of early removal of visual input via bilateral enucleation at birth. To understand the long-term effects of early blindness we conducted anatomical and molecular assays 18 months after enucleation, near the end of lifespan in the mouse. Bilateral enucleation early in life leads to long-term, stable size reductions of the thalamic lateral geniculate nucleus (LGN) and the primary visual cortex (V1) alongside a increase in individual whisker barrel size. Neocortical gene expression in the aging brain has not been previously identified; we document cortical expression of multiple regionalization genes. Expression patterns of Ephrin A5, COUP-TFI, and RZRβ and patterns of intraneocortical connectivity (INC) are altered in the neocortices of aging blind mice. Sensory inputs from different modalities during development likely play a major role in the development of cortical areal and thalamic nuclear boundaries. We suggest that early patterning by prenatal retinal activity combined with persistent gene expression within the thalamus and cortex is sufficient to establish and preserve a small but present LGN and V1 into late adulthood.

No MeSH data available.


Related in: MedlinePlus