Ryutaro Akiba, Shane Lind Boniec, Sharm Knecht, Hirofumi Uyama, Hung-Ya Tu, Takayuki Baba, Masayo Takahashi, Michiko Mandai, Rachel O Wong
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We thus used serial block-face electron microscopy to determine the degree of plasticity and potential remodeling of this pathway in adult <i>Macaca fascicularis</i> several months after acute photoreceptor loss upon photocoagulation. We reconstructed MBC structure and connectivity within and adjacent to the region of cone loss. We found that MBC dendrites within the scotoma retracted and failed to reach surviving cones to form new connections. However, both surviving cones and ON and OFF MBC dendrites at the scotoma border exhibited remodeling, suggesting that these neurons can demonstrate plasticity and rewiring at maturity. At six months postlesion, disconnected OFF MBCs clearly lost output ribbon synapses with their postsynaptic partners, whereas the majority of ON MBCs maintained their axonal ribbon numbers, suggesting differential timing or extent in ON and OFF midget circuit remodeling after cone loss. 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引用次数: 0
摘要
人类和非人灵长类动物的视网膜眼窝对高敏锐度和色觉至关重要。眼窝内有专门的电路,其中来自单个锥体感光器的信号主要传递给一个导通型和一个关断型中层双极细胞(MBC),后者又分别连接到一个导通型或关断型中层神经节细胞(MGC)。恢复眼窝视力不仅需要更换光感受器,还需要与存活的ON型和OFF型中枢双极细胞和中枢神经节细胞进行适当的重新连接。然而,我们目前对视锥缺失对残存的眼窝侏儒通路的影响了解有限。因此,我们使用序列块面电子显微镜来确定成年猕猴在光凝后急性光感受器缺失数月后这一通路的可塑性和潜在重塑程度。我们重建了锥体缺失区域内和邻近区域的 MBC 结构和连接性。我们发现,视网膜瘤内的MBC树突回缩,无法到达存活的视锥形成新的连接。然而,幸存的锥体和位于视网膜瘤边界的导通和断开MBC树突都表现出重塑,这表明这些神经元在成熟期可以表现出可塑性和重新布线。在锥体缺失后六个月,断开连接的OFF MBC明显失去了与其突触后伙伴的输出带状突触,而大多数ON MBC保持了其轴突带状突触的数量,这表明锥体缺失后ON和OFF midget回路重塑的时间或程度不同。我们的研究结果提出了在恢复眼窝视力的细胞替代方法中重新布线的考虑因素。
Cellular and circuit remodeling of the primate foveal midget pathway after acute photoreceptor loss.
The retinal fovea in human and nonhuman primates is essential for high acuity and color vision. Within the fovea lies specialized circuitry in which signals from a single cone photoreceptor are largely conveyed to one ON and one OFF type midget bipolar cell (MBC), which in turn connect to a single ON or OFF midget ganglion cell (MGC), respectively. Restoring foveal vision requires not only photoreceptor replacement but also appropriate reconnection with surviving ON and OFF MBCs and MGCs. However, our current understanding of the effects of cone loss on the remaining foveal midget pathway is limited. We thus used serial block-face electron microscopy to determine the degree of plasticity and potential remodeling of this pathway in adult Macaca fascicularis several months after acute photoreceptor loss upon photocoagulation. We reconstructed MBC structure and connectivity within and adjacent to the region of cone loss. We found that MBC dendrites within the scotoma retracted and failed to reach surviving cones to form new connections. However, both surviving cones and ON and OFF MBC dendrites at the scotoma border exhibited remodeling, suggesting that these neurons can demonstrate plasticity and rewiring at maturity. At six months postlesion, disconnected OFF MBCs clearly lost output ribbon synapses with their postsynaptic partners, whereas the majority of ON MBCs maintained their axonal ribbon numbers, suggesting differential timing or extent in ON and OFF midget circuit remodeling after cone loss. Our findings raise rewiring considerations for cell replacement approaches in the restoration of foveal vision.
期刊介绍:
The Proceedings of the National Academy of Sciences (PNAS), a peer-reviewed journal of the National Academy of Sciences (NAS), serves as an authoritative source for high-impact, original research across the biological, physical, and social sciences. With a global scope, the journal welcomes submissions from researchers worldwide, making it an inclusive platform for advancing scientific knowledge.