Suppr超能文献

胆碱能视网膜波的破坏会改变视觉皮层的发育和功能。

Disruption of Cholinergic Retinal Waves Alters Visual Cortex Development and Function.

作者信息

Burbridge Timothy J, Ratliff Jacob M, Dwivedi Deepanjali, Vrudhula Uma, Alvarado-Huerta Francisco, Sjulson Lucas, Ibrahim Leena Ali, Cheadle Lucas, Fishell Gordon, Batista-Brito Renata

机构信息

Department of Neurobiology, Harvard Medical School, 220 Longwood Ave., Boston, MA 02115.

Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461.

出版信息

bioRxiv. 2024 Apr 15:2024.04.05.588143. doi: 10.1101/2024.04.05.588143.

Abstract

Retinal waves represent an early form of patterned spontaneous neural activity in the visual system. These waves originate in the retina before eye-opening and propagate throughout the visual system, influencing the assembly and maturation of subcortical visual brain regions. However, because it is technically challenging to ablate retina-derived cortical waves without inducing compensatory activity, the role these waves play in the development of the visual cortex remains unclear. To address this question, we used targeted conditional genetics to disrupt cholinergic retinal waves and their propagation to select regions of primary visual cortex, which largely prevented compensatory patterned activity. We find that loss of cholinergic retinal waves without compensation impaired the molecular and synaptic maturation of excitatory neurons located in the input layers of visual cortex, as well as layer 1 interneurons. These perinatal molecular and synaptic deficits also relate to functional changes observed at later ages. We find that the loss of perinatal cholinergic retinal waves causes abnormal visual cortex retinotopy, mirroring changes in the retinotopic organization of gene expression, and additionally impairs the processing of visual information. We further show that retinal waves are necessary for higher order processing of sensory information by impacting the state-dependent activity of layer 1 interneurons, a neuronal type that shapes neocortical state-modulation, as well as for state-dependent gain modulation of visual responses of excitatory neurons. Together, these results demonstrate that a brief targeted perinatal disruption of patterned spontaneous activity alters early cortical gene expression as well as synaptic and physiological development, and compromises both fundamental and, notably, higher-order functions of visual cortex after eye-opening.

摘要

视网膜波是视觉系统中一种早期形式的有模式的自发神经活动。这些波在睁眼之前起源于视网膜,并传播到整个视觉系统,影响皮质下视觉脑区的组装和成熟。然而,由于在不诱导代偿性活动的情况下消融源自视网膜的皮质波在技术上具有挑战性,这些波在视觉皮质发育中所起的作用仍不清楚。为了解决这个问题,我们使用靶向条件遗传学来破坏胆碱能视网膜波及其向初级视觉皮质选定区域的传播,这在很大程度上防止了代偿性模式活动。我们发现,胆碱能视网膜波缺失且无代偿会损害位于视觉皮质输入层的兴奋性神经元以及第1层中间神经元的分子和突触成熟。这些围产期分子和突触缺陷也与在较晚年龄观察到的功能变化有关。我们发现,围产期胆碱能视网膜波的缺失会导致视觉皮质视网膜拓扑异常,反映基因表达的视网膜拓扑组织变化,此外还会损害视觉信息的处理。我们进一步表明,视网膜波对于感觉信息的高阶处理是必要的,这是通过影响第1层中间神经元的状态依赖性活动来实现的,第1层中间神经元是一种塑造新皮质状态调制的神经元类型,同时也参与兴奋性神经元视觉反应的状态依赖性增益调制。总之,这些结果表明,围产期对有模式的自发活动进行短暂的靶向破坏会改变早期皮质基因表达以及突触和生理发育,并损害睁眼后视觉皮质的基本功能,尤其是高阶功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa1/11030223/f136a4bf0811/nihpp-2024.04.05.588143v2-f0001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验