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Ultra-large mesoscopic imaging advances in the cortex open new pathways to develop neuroprosthetics to restore foveal vision in blind patients. Using targeted optogenetic activation, an optical prosthetic can focally stimulate spatially localized lateral geniculate nucleus (LGN) synaptic boutons within the primary visual cortex (V1). If we localize a cluster within a specific hypercolumn’s input layer, we will find that activation of a subset of these boutons is perceptually fungible with the activation of a different subset of boutons from the same hypercolumn input module. By transducing these LGN neurons with light-sensitive proteins, they are now sensitive to light and we can optogenetically stimulate them in a pattern mimicking naturalistic visual input. Optogenetic targeting of these purely glutamatergic inputs is free from unwanted co-activation of inhibitory neurons (a common problem in electrode-based prosthetic devices, which result in diminished contrast perception). We must prosthetically account for rapidly changing cortical activity and gain control, so our system integrates a real-time cortical read-out mechanism to continually assess and provide feedback to modify stimulation levels, just as the natural visual system does. We accomplish this by readingout a multi-colored array of genetically-encoded and transduced bioluminescent calcium responses in V1 neurons. This hyperspectral array of colors can achieve single-cell resolution. By tracking eye movements in the blind patients, we will account for oculomotor effects by adjusting the contemporaneous stimulation of the LGN boutons to mimic the effects of natural vision, including those from eye movements. This system, called the Optogenetic Brain System (OBServ), is designed to function by optimally activating visual responses in V1 from a fully-implantable coplanar emitter array coupled with a video camera and a bioluminescent read-out system. It follows that if we stimulate the LGN input modules in the same pattern as natural vision, the recipient should perceive naturalistic prosthetic vision. As such, the system holds the promise of restoring vision in the blind at the highest attainable acuity, with maximal contrast sensitivity, using an integrated nanophotonic implantable device that receives eye-tracked video input from a head-mounted video camera, using relatively non-invasive prosthetic technology that does not cross the pia mater of the brain.
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A theory of direction selectivity for macaque primary visual cortex
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.
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- Award ID(s):
- 1734854
- PAR ID:
- 10284670
- Publisher / Repository:
- Proceedings of the National Academy of Sciences
- Date Published:
- Journal Name:
- Proceedings of the National Academy of Sciences
- Volume:
- 118
- Issue:
- 32
- ISSN:
- 0027-8424
- Page Range / eLocation ID:
- Article No. e2105062118
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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