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.
Highlights
Distinct sensory and motor regions are generated through patterning of the nervous system during mammalian development
We observed a positional shift in expression of ephrin A5 and a corollary shift in intraneocortical connectivity (INC) projections at the somatosensory-visual border, highlighting short-term plasticity that occurred before natural eye opening
Building on these initial findings in young animals the present report seeks to determine the range of effects of early bilateral enucleation on the anatomical, connectional and gene expression patterns in the aging mouse
Summary
Distinct sensory and motor regions are generated through patterning of the nervous system during mammalian development. These regions represent discrete subunits of an elaborate network regulating multi-sensory integration, complex motor function and other high-level processes. Information from sensory receptors (such as those found in the cochlea, skin and retina) are relayed to the neocortex via thalamocortical afferents (TCAs) from distinct thalamic nuclei. This input is processed in a modality-specific manner, resulting in perception. How and why the brain ages is not fully understood, but most agree that a decline in neurotransmitter function, generation of reactive oxygen species, dysregulation of calcium signaling, and mitochondrial dysfunction are involved in the maladaptive features of brain aging (Mattson et al, 2002; Burke and Barnes, 2006; Toescu and Verkhratsky, 2007)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
