scholarly journals Spike-triggered average electrical stimuli as input filters for bionic vision – a perspective.

Author(s):  
Daniel Rathbun ◽  
Nima Ghorbani ◽  
Hamed Shabani ◽  
Eberhart Zrenner ◽  
Zohreh Hosseinzadeh

Bionic retinal implants are gaining acceptance in the treatment of blindness from degenerative diseases including retinitis pigmentosa and macular degeneration. A current obstacle to the improved performance of such implants is the difficulty of comparing the results of disparate experiments. Another obstacle is the current difficulty in selectively activating the many different retinal ganglion cell types that are used as separate pathways for visual information to the brain. To address these obstacles, we propose a modelling framework based on white noise stimulation and reverse correlation.In this perspective, we first outline early developments in visual retinal physiology leading up to the implementation of white noise stimuli and spike-triggered averaging. We then review recent efforts to adapt the white noise method for electrical stimulation of the retina and some of the nuances of this approach. Based on such white noise methods, we describe a modelling framework whereby the effect of any arbitrary electrical stimulus on a ganglion cell’s neural code can be better understood. This framework should additionally disentangle the effects of stimulation on photoreceptor, bipolar cell and retinal ganglion cell – ultimately supporting selective stimulation of specific ganglion cell types for a more nuanced bionic retinal implant. Finally, we point to upcoming considerations in this rapidly developing domain of research.

2020 ◽  
Author(s):  
Nadia Parmhans ◽  
Anne Drury Fuller ◽  
Eileen Nguyen ◽  
Katherine Chuang ◽  
David Swygart ◽  
...  

AbstractMembers of the POU4F/Brn3 transcription factor family have an established role in the development of retinal ganglion cell types (RGCs), the projection sensory neuron conveying visual information from the mammalian eye to the brain. Our previous work using sparse random recombination of a conditional knock-in reporter allele expressing Alkaline Phosphatase (AP) and intersectional genetics had identified three types of Pou4f3/Brn3c positive (Brn3c+) RGCs. Here, we describe a novel Brn3cCre mouse allele generated by serial Dre to Cre recombination. We use this allele to explore the expression overlap of Brn3c with Brn3a and Brn3b and the dendritic arbor morphologies and visual stimulus properties of Brn3c+ RGC types. Furthermore, we explore Brn3c-expressing brain nuclei. Our analysis reveals a much larger number of Brn3c+ RGCs and more diverse set of RGC types than previously reported. The majority of RGCs having expressed Brn3c during development are still Brn3c positive in the adult, and all of them express Brn3a while only about half express Brn3b. Intersection of Brn3b and Brn3c expression highlights an area of increased RGC density, similar to an area centralis, corresponding to part of the binocular field of view of the mouse. Brn3c+ neurons and projections are present in multiple brain nuclei. Brn3c+ RGC projections can be detected in the Lateral Geniculate Nucleus (LGN), Pretectal Area (PTA) and Superior Colliculus (SC) but also in the thalamic reticular nucleus (TRN), a visual circuit station that was not previously described to receive retinal input. Most Brn3c+ neurons of the brain are confined to the pretectum and the dorsal midbrain. Amongst theses we identify a previously unknown Brn3c+ subdivision of the deep mesencephalic nucleus (DpMe). Thus, our newly generated allele provides novel biological insights into RGC type classification, brain connectivity and midbrain cytoarchitectonic, and opens the avenue for specific characterization and manipulation of these structures.


2019 ◽  
Vol 486 (2) ◽  
pp. 258-261
Author(s):  
L. E. Petrovskaya ◽  
M. V. Roshchin ◽  
G. R. Smirnova ◽  
D. E. Kolotova ◽  
P. M. Balaban ◽  
...  

For the purpose of optogenetic prosthetics of the receptive field of the retinal ganglion cell, we have created a bicistronic genetic construct that carries genes of excitatory (channelorhodopsin2) and inhibitory (anionic channelorhodopsin) rhodopsins. A distinctive feature of this construct is the combination of two genes into one construct with the mutant IRES inserted between them, which ensures precise ratio of the expression levels of the first and second gene in each transfected cell. It was found that the illumination of the central part of transfected neuron with light with a wavelength of 470 nm causes the generation of action potentials in the cell. At the same time, light stimulation of the periphery of the neuron causes cessation of the generation of action potentials. Thus, we were able to simulate the ON-OFF interaction of the receptive field of the retinal ganglion cell using optogenetic methods. Theoretically, this construction can be used for optogenetic prosthetics of degenerative retina in case of its delivery to ganglion cells using lentiviral vectors.


Neuron ◽  
2017 ◽  
Vol 94 (6) ◽  
pp. 1112-1120.e4 ◽  
Author(s):  
Michael W. Norsworthy ◽  
Fengfeng Bei ◽  
Riki Kawaguchi ◽  
Qing Wang ◽  
Nicholas M. Tran ◽  
...  

Development ◽  
2021 ◽  
Author(s):  
Si Chen ◽  
Kira L. Lathrop ◽  
Takaaki Kuwajima ◽  
Jeffrey M. Gross

Visual information is transmitted from the eye to the brain along the optic nerve, a structure composed of retinal ganglion cell (RGC) axons. The optic nerve is highly vulnerable to damage in neurodegenerative diseases like glaucoma and there are currently no FDA-approved drugs or therapies to protect RGCs from death. Zebrafish possess remarkable neuroprotective and regenerative abilities and here, utilizing an optic nerve transection (ONT) injury and an RNA-seq-based approach, we identify genes and pathways active in RGCs that may modulate their survival. Through pharmacological perturbation, we demonstrate that JAK/STAT pathway activity is required for RGC survival after ONT. Furthermore, we show that immune responses directly contribute to RGC death after ONT; macrophages/microglia are recruited to the retina and blocking neuroinflammation or depleting these cells after ONT rescues survival of RGCs. Taken together, these data support a model in which crosstalk between macrophages/microglia and RGCs, mediated by Jak/Stat pathway activity, regulates RGC survival after optic nerve injury.


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