Abbott Charles W, Kozanian Olga O, Huffman Kelly J
Interdisciplinary Neuroscience Graduate Program, University of California, Riverside Riverside, CA, USA.
Department of Psychology, University of California, Riverside Riverside, CA, USA.
Front Aging Neurosci. 2015 Jul 24;7:144. doi: 10.3389/fnagi.2015.00144. eCollection 2015.
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.
哺乳动物新皮层的发育受神经模式形成机制调控，不同的感觉和运动区域通过区域化过程产生。这种发育与中枢或外周感觉系统的发育同时发生。具体而言，新皮层在发育过程中分割为具有不同细胞结构、连接性和功能的特定区域，这既依赖于皮层内在机制，如基因表达，也依赖于外在过程，如感觉受体的输入。随着动物年龄增长，这个发育程序从模式形成转变为维持，并且被认为在整个生命过程中都是活跃的，在此过程中大脑的组织是稳定但具有可塑性的。在本研究中，我们描述了出生时通过双侧眼球摘除术早期去除视觉输入的长期影响。为了了解早期失明的长期影响，我们在眼球摘除术后18个月，即小鼠寿命接近尾声时，进行了解剖学和分子检测。生命早期的双侧眼球摘除导致丘脑外侧膝状体核（LGN）和初级视觉皮层（V1）长期、稳定地缩小，同时单个触须桶状结构增大。此前尚未确定衰老大脑中新皮层的基因表达情况；我们记录了多个区域化基因的皮层表达。在衰老的失明小鼠新皮层中，Ephrin A5、COUP-TFI和RZRβ的表达模式以及皮层内连接（INC）模式发生了改变。发育过程中来自不同感觉模态的输入可能在皮层区域和丘脑核边界的发育中起主要作用。我们认为，产前视网膜活动的早期模式形成与丘脑和皮层内持续的基因表达相结合，足以在成年后期建立并保留一个虽小但存在的LGN和V1。
