Cellular and circuit remodeling of the primate foveal midget pathway after acute photoreceptor loss

• 成果类型: Article
• 署名作者: Akiba, Ryutaro; Boniec, Shane Lind; Knecht, Sharm; Uyama, Hirofumi; Tu, Hung- Ya; Baba, Takayuki; Takahashi, Masayo; Mandai, Michiko; Wong, Rachel O.
• 署名单位: University of Washington; University of Washington Seattle; RIKEN; Chiba University; University of Osaka
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14397
• DOI: 10.1073/pnas.2413104121
• 发表日期: 2024-09-10
• 关键词: bipolar cells; mouse model; cone photoreceptors; synapse formation; horizontal cells; on-center; transplantation; retina; rod; abnormalities

摘要

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.