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Contemporary regenerative therapies have introduced stem-like cells to replace damaged neurons in the visual system by recapitulating critical processes of eye development. The collective migration of neural stem cells is fundamental to retinogenesis and has been exceptionally well-studied using the fruit fly model of Drosophila Melanogaster. However, the migratory behavior of its retinal neuroblasts (RNBs) has been surprisingly understudied, despite being critical to retinal development in this invertebrate model. The current project developed a new microfluidic system to examine the collective migration of RNBs extracted from the developing visual system of Drosophila as a model for the collective motile processes of replacement neural stem cells. The system scales with the microstructure of the Drosophila optic stalk, which is a pre-cursor to the optic nerve, to produce signaling fields spatially comparable to in vivo RNB stimuli. Experiments used the micro-optic stalk system, or μOS, to demonstrate the preferred sizing and directional migration of collective, motile RNB groups in response to changes in exogenous concentrations of fibroblast growth factor (FGF), which is a key factor in development. Our data highlight the importance of cell-to-cell contacts in enabling cell cohesion during collective RNB migration and point to the unexplored synergy of invertebrate cell study and microfluidic platforms to advance regenerative strategies.
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Eye structure shapes neuron function in Drosophila motion vision
Summary Many animals rely on vision to navigate through their environment. The pattern of changes in the visual scene induced by self-motion is theoptic flow1, which is first estimated in local patches by directionally selective (DS) neurons2–4. But how should the arrays of DS neurons, each responsive to motion in a preferred direction at a specific retinal position, be organized to support robust decoding of optic flow by downstream circuits? Understanding this global organization is challenging because it requires mapping fine, local features of neurons across the animal’s field of view3. InDrosophila, the asymmetric dendrites of the T4 and T5 DS neurons establish their preferred direction, making it possible to predict DS responses from anatomy4,5. Here we report that the preferred directions of fly DS neurons vary at different retinal positions and show that this spatial variation is established by the anatomy of the compound eye. To estimate the preferred directions across the visual field, we reconstructed hundreds of T4 neurons in a full brain EM volume6and discovered unexpectedly stereotypical dendritic arborizations that are independent of location. We then used whole-head μCT scans to map the viewing directions of all compound eye facets and found a non-uniform sampling of visual space that explains the spatial variation in preferred directions. Our findings show that the organization of preferred directions in the fly is largely determined by the compound eye, exposing an intimate and unexpected connection between the peripheral structure of the eye, functional properties of neurons deep in the brain, and the control of body movements.
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- Award ID(s):
- 2014862
- PAR ID:
- 10623801
- Publisher / Repository:
- bioRxiv
- Date Published:
- Format(s):
- Medium: X
- Institution:
- bioRxiv
- Sponsoring Org:
- National Science Foundation
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This paper offers a theory for the origin of direction selectivity (DS) in the macaque primary visual cortex, V1. DS is essential for the perception of motion and control of pursuit eye movements. In the macaque visual pathway, neurons with DS first appear in V1, in the Simple cell population of the Magnocellular input layer 4Cα. The lateral geniculate nucleus (LGN) cells that project to these cortical neurons, however, are not direction selective. We hypothesize that DS is initiated in feed-forward LGN input, in the summed responses of LGN cells afferent to a cortical cell, and it is achieved through the interplay of 1) different visual response dynamics of ON and OFF LGN cells and 2) the wiring of ON and OFF LGN neurons to cortex. We identify specific temporal differences in the ON/OFF pathways that, together with item 2, produce distinct response time courses in separated subregions; analysis and simulations confirm the efficacy of the mechanisms proposed. To constrain the theory, we present data on Simple cells in layer 4Cα in response to drifting gratings. About half of the cells were found to have high DS, and the DS was broadband in spatial and temporal frequency (SF and TF). The proposed theory includes a complete analysis of how stimulus features such as SF and TF interact with ON/OFF dynamics and LGN-to-cortex wiring to determine the preferred direction and magnitude of DS.more » « less
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Posted Content:
- https://doi.org/10.1101/2022.12.14.520178
