scholarly journals A novel approach to the functional classification of retinal ganglion cells

2021 ◽  
Author(s):  
Gerrit Hilgen ◽  
Evgenia Kartsaki ◽  
Viktoriia Kartysh ◽  
Bruno Cessac ◽  
Evelyne Sernagor
Keyword(s):  
Large Scale ◽  
Ganglion Cells ◽  
Brain Regions ◽  
Designer Drugs ◽  
Retinal Ganglion ◽  
Novel Approach ◽  
Functional Features ◽  
Novel Strategy ◽  
Post Hoc ◽  
Multiple Clusters

Retinal neurons come in remarkable diversity based on structure, function and genetic identity. Classifying these cells is a challenging task, requiring multimodal methodology. Here, we introduce a novel approach for retinal ganglion cell (RGC) classification, based on pharmacogenetics combined with immunohistochemistry and large-scale retinal electrophysiology. Our novel strategy allows grouping of cells sharing gene expression and understanding how these cell classes respond to basic and complex visual scenes. Our approach consists of increasing the firing level of RGCs co-expressing a certain gene (Scnn1a or Grik4) using excitatory DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) and then correlate the location of these cells with post hoc immunostaining, to unequivocally characterize anatomical and functional features of these two groups. We grouped these isolated RGC responses into multiple clusters based on the similarity of the spike trains. With our approach, and accompanied by immunohistochemistry, we were able to extend the pre-existing list of Grik4 expressing RGC types to a total of 8 RGC types and, for the first time, we provide a phenotypical description of 14 Scnn1a-expressing RGCs. The insights and methods gained here can guide RGC classification but also neuronal classification challenges in other brain regions.

scholarly journals Strong and specific connections between retinal axon mosaics and midbrain neurons revealed by large scale paired recordings

2021 ◽  
Author(s):  
Jérémie Sibille ◽  
Carolin Gehr ◽  
Jonathan I. Benichov ◽  
Hymavathy Balasubramanian ◽  
Kai Lun Teh ◽  
...  
Keyword(s):  
Single Cell ◽  
Retinal Ganglion Cells ◽  
Large Scale ◽  
Ganglion Cells ◽  
Brain Regions ◽  
High Density ◽  
List Type ◽  
Retinal Ganglion ◽  
Midbrain Neurons

SUMMARYThe superior colliculus (SC) is a midbrain structure that plays important roles in visually guided behaviors. Neurons in the SC receive afferent inputs from retinal ganglion cells (RGC), the output cells of the retina, but how SC neurons integrate RGC activity in vivo is unknown. SC neurons might be driven by strong but sparse retinal inputs, thereby reliably transmitting specific retinal functional channels. Alternatively, SC neurons could sum numerous but weak inputs, thereby extracting new features by combining a diversity of retinal signals. Here, we discovered that high-density electrodes simultaneously capture the activity and the location of large populations of retinal axons and their postsynaptic SC target neurons, permitting us to investigate the retinocollicular circuit on a structural and functional level in vivo. We show that RGC axons in the mouse are organized in mosaics that provide a single cell precise representation of the retina as input to SC. This isomorphic mapping between retina and SC builds the scaffold for highly specific wiring in the retinocollicular circuit which we show is characterized by strong connections and limited functional convergence, established in log-normally distributed connection strength. Because our novel method of large-scale paired recordings is broadly applicable for investigating functional connectivity across brain regions, we were also able to identify retinal inputs to the avian optic tectum of the zebra finch. We found common wiring rules in mammals and birds that provide a precise and reliable representation of the visual world encoded in RGCs to neurons in retinorecipient areas.HIGHLIGHTSHigh-density electrodes capture the activity of afferent axons and target neurons in vivoRetinal ganglion cells axons are organized in mosaicsSingle cell precise isomorphism between dendritic and axonal RGC mosaicsMidbrain neurons are driven by sparse but strong retinal inputsFunctional wiring of the retinotectal circuit is similar in mammals and birds

scholarly journals Architecture of retinal projections to the central circadian pacemaker

2016 ◽  
Vol 113 (21) ◽  
pp. 6047-6052 ◽  
Author(s):  
Diego Carlos Fernandez ◽  
Yi-Ting Chang ◽  
Samer Hattar ◽  
Shih-Kuo Chen
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Microscopic Analysis ◽  
Brain Regions ◽  
Retinal Ganglion ◽  
Circadian Pacemaker ◽  
Retinal Neurons ◽  
Retinal Input ◽  
Innervation Patterns ◽  
Left And Right

The suprachiasmatic nucleus (SCN) receives direct retinal input from the intrinsically photosensitive retinal ganglion cells (ipRGCs) for circadian photoentrainment. Interestingly, the SCN is the only brain region that receives equal inputs from the left and right eyes. Despite morphological assessments showing that axonal fibers originating from ipRGCs cover the entire SCN, physiological evidence suggests that only vasoactive intestinal polypeptide (VIP)/gastrin-releasing peptide (GRP) cells located ventrally in the SCN receive retinal input. It is still unclear, therefore, which subpopulation of SCN neurons receives synaptic input from the retina and how the SCN receives equal inputs from both eyes. Here, using single ipRGC axonal tracing and a confocal microscopic analysis in mice, we show that ipRGCs have elaborate innervation patterns throughout the entire SCN. Unlike conventional retinal ganglion cells (RGCs) that innervate visual targets either ipsilaterally or contralaterally, a single ipRGC can bilaterally innervate the SCN. ipRGCs form synaptic contacts with major peptidergic cells of the SCN, including VIP, GRP, and arginine vasopressin (AVP) neurons, with each ipRGC innervating specific subdomains of the SCN. Furthermore, a single SCN-projecting ipRGC can send collateral inputs to many other brain regions. However, the size and complexity of the axonal arborizations in non-SCN regions are less elaborate than those in the SCN. Our results provide a better understanding of how retinal neurons connect to the central circadian pacemaker to synchronize endogenous circadian clocks with the solar day.

scholarly journals Multiplexed computations in retinal ganglion cells of a single type

2016 ◽  
Author(s):  
Stephane Deny ◽  
Ulisse Ferrari ◽  
Emilie Mace ◽  
Pierre Yger ◽  
Romain Caplette ◽  
...  
Keyword(s):  
Large Scale ◽  
Ganglion Cells ◽  
Quantitative Model ◽  
Visual Scene ◽  
Single Type ◽  
Retinal Ganglion ◽  
Object Code ◽  
Stimulus Feature ◽  
Homogeneous Population ◽  
Common Assumption

AbstractIn the early visual system, cells of the same type perform the same computation in di↵erent places of the visual field. How these cells code together a complex visual scene is unclear. A common assumption is that cells of the same type will extract a single stimulus feature to form a feature map, but this has rarely been observed directly. Using large-scale recordings in the rat retina, we show that a homogeneous population of fast OFF ganglion cells simultaneously encodes two radically different features of a visual scene. Cells close to a moving object code linearly for its position, while distant cells remain largely invariant to the object’s position and, instead, respond non-linearly to changes in the object’s speed. Cells switch between these two computations depending on the stimulus. We developed a quantitative model that accounts for this effect and identified a likely disinhibitory circuit that mediates it. Ganglion cells of a single type thus do not code for one, but two features simultaneously. This richer, flexible neural map might also be present in other sensory systems.

scholarly journals A projection specific logic to sampling visual inputs in mouse superior colliculus

2018 ◽  
Author(s):  
Katja Reinhard ◽  
Chen Li ◽  
Quan Do ◽  
Emily Burke ◽  
Steven Heynderickx ◽  
...  
Keyword(s):  
Superior Colliculus ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Sensory Information ◽  
Cell Types ◽  
Brain Regions ◽  
Visual Response ◽  
Retinal Ganglion ◽  
Parabigeminal Nucleus

AbstractUsing sensory information to trigger different behaviours relies on circuits that pass-through brain regions. However, the rules by which parallel inputs are routed to different downstream targets is poorly understood. The superior colliculus mediates a set of innate behaviours, receiving input from ~30 retinal ganglion cell types and projecting to behaviourally important targets including the pulvinar and parabigeminal nucleus. Combining transsynaptic circuit tracing with in-vivo and ex-vivo electrophysiological recordings we observed a projection specific logic where each collicular output pathway sampled a distinct set of retinal inputs. Neurons projecting to the pulvinar or parabigeminal nucleus uniquely sampled 4 and 7 cell types, respectively. Four others innervated both pathways. The visual response properties of retinal ganglion cells correlated well with those of their disynaptic targets. These findings suggest that projection specific sampling of retinal inputs forms a mechanistic basis for the selective triggering of visually guided behaviours by the superior colliculus.

scholarly journals Pan-Retinal Characterisation of Light Responses from Ganglion Cells in the Developing Mouse Retina

2016 ◽  
Author(s):  
Gerrit Hilgen ◽  
Sahar Pirmoradian ◽  
Daniela Pamplona ◽  
Pierre Kornprobst ◽  
Bruno Cessac ◽  
...  
Keyword(s):  
Large Scale ◽  
Ganglion Cells ◽  
Mouse Retina ◽  
Multielectrode Array ◽  
Retinal Ganglion ◽  
Developmental Profile ◽  
Light Responses ◽  
Ecological Requirements ◽  
Eye Opening ◽  
Dorsal Retina

AbstractWe have investigated the ontogeny of light-driven responses in mouse retinal ganglion cells (RGCs). Using a large-scale, high-density multielectrode array, we recorded from hundreds to thousands of RGCs simultaneously at pan-retinal level, including dorsal and ventral locations. Responses to different contrasts not only revealed a complex developmental profile for ON, OFF and ON-OFF RGC types, but also unveiled differences between dorsal and ventral RGCs. At eye-opening, dorsal RGCs of all types were more responsive to light, perhaps indicating an environmental priority to nest viewing for pre-weaning pups. The developmental profile of ON and OFF RGCs exhibited antagonistic behavior, with the strongest ON responses shortly after eye-opening, followed by an increase in the strength of OFF responses later on. Further, we found that with maturation receptive field (RF) center sizes decrease, responses to light get stronger, and centers become more circular while seeing differences in all of them between RGC types. These findings show that retinal functionality is not spatially homogeneous, likely reflecting ecological requirements that favour the early development of dorsal retina, and reflecting different roles in vision in the mature animal.

The multiple factors determining retinotopic order in the growth of optic fibres into the optic tectum

1977 ◽  
Vol 278 (961) ◽  
pp. 261-276 ◽  
Keyword(s):  
Optic Tectum ◽  
Nervous Tissue ◽  
Large Scale ◽  
Ganglion Cells ◽  
Impulse Activity ◽  
Nerve Impulse ◽  
Retinal Ganglion ◽  
Optic Nerve Fibre ◽  
Cells Of Origin ◽  
Lower Vertebrates

Evidence is presented to support the conclusion that normally functioning optic nerve fibre terminal arborizations are open to continuous modification of their location and that they are capable of large scale gradual movement across the optic tectum in lower vertebrates. The termination of optic fibres at precisely defined tectal locations during normal embryonic development does not appear, in view of this and other evidence, to be due to any restrictions imposed by specializations distinguishing terminal sites themselves. However, there is clear evidence that, on the basis of possibly very simple specializations acquired as part of their embryological origin at particular locations in the retina, growing optic fibres actively and continuously select specific routes to be followed through intervening nervous tissue which eventually lead them to predictable and at least approximately appropriate terminal regions in the tectum. It is proposed that terminals move into and maintain fully retinotopic order as a result of direct interactions between fibres themselves based on features correlated with the retinal proximity of their cells of origin. This may involve further use of specializations due to related embryological origin: correlations in nerve impulse activity among neighbouring retinal ganglion cells may serve to stabilize most favourable terminal combinations. It is argued that fibres are subject to multiple influences which contribute to their orderly growth and that the demands made on the embryological differentiation of nervous tissue can thereby be considerably reduced.

scholarly journals Activation of ganglion cells and axon bundles using epiretinal electrical stimulation

2017 ◽  
Vol 118 (3) ◽  
pp. 1457-1471 ◽  
Author(s):  
Lauren E. Grosberg ◽  
Karthik Ganesan ◽  
Georges A. Goetz ◽  
Sasidhar S. Madugula ◽  
Nandita Bhaskhar ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Retinal Ganglion Cells ◽  
Large Scale ◽  
Ganglion Cells ◽  
Propagation Speed ◽  
Peripheral Retina ◽  
Retinal Ganglion ◽  
Central Retina ◽  
Axon Bundle ◽  
Stimulation Current

Epiretinal prostheses for treating blindness activate axon bundles, causing large, arc-shaped visual percepts that limit the quality of artificial vision. Improving the function of epiretinal prostheses therefore requires understanding and avoiding axon bundle activation. This study introduces a method to detect axon bundle activation on the basis of its electrical signature and uses the method to test whether epiretinal stimulation can directly elicit spikes in individual retinal ganglion cells without activating nearby axon bundles. Combined electrical stimulation and recording from isolated primate retina were performed using a custom multielectrode system (512 electrodes, 10-μm diameter, 60-μm pitch). Axon bundle signals were identified by their bidirectional propagation, speed, and increasing amplitude as a function of stimulation current. The threshold for bundle activation varied across electrodes and retinas, and was in the same range as the threshold for activating retinal ganglion cells near their somas. In the peripheral retina, 45% of electrodes that activated individual ganglion cells (17% of all electrodes) did so without activating bundles. This permitted selective activation of 21% of recorded ganglion cells (7% of expected ganglion cells) over the array. In one recording in the central retina, 75% of electrodes that activated individual ganglion cells (16% of all electrodes) did so without activating bundles. The ability to selectively activate a subset of retinal ganglion cells without axon bundles suggests a possible novel architecture for future epiretinal prostheses. NEW & NOTEWORTHY Large-scale multielectrode recording and stimulation were used to test how selectively retinal ganglion cells can be electrically activated without activating axon bundles. A novel method was developed to identify axon activation on the basis of its unique electrical signature and was used to find that a subset of ganglion cells can be activated at single-cell, single-spike resolution without producing bundle activity in peripheral and central retina. These findings have implications for the development of advanced retinal prostheses.

scholarly journals Nonlinear decoding of natural images from large-scale primate retinal ganglion recordings

2020 ◽  
Author(s):  
Young Joon Kim ◽  
Nora Brackbill ◽  
Ella Batty ◽  
JinHyung Lee ◽  
Catalin Mitelut ◽  
...  
Keyword(s):  
Visual Information ◽  
Large Scale ◽  
Ganglion Cells ◽  
State Of The Art ◽  
Fundamental Problem ◽  
The State ◽  
Natural Images ◽  
Retinal Ganglion ◽  
Neural Decoding ◽  
Sensory Stimuli

AbstractDecoding sensory stimuli from neural activity can provide insight into how the nervous system might interpret the physical environment, and facilitates the development of brain-machine interfaces. Nevertheless, the neural decoding problem remains a significant open challenge. Here, we present an efficient nonlinear decoding approach for inferring natural scene stimuli from the spiking activities of retinal ganglion cells (RGCs). Our approach uses neural networks to improve upon existing decoders in both accuracy and scalability. Trained and validated on real retinal spike data from > 1000 simultaneously recorded macaque RGC units, the decoder demonstrates the necessity of nonlinear computations for accurate decoding of the fine structures of visual stimuli. Specifically, high-pass spatial features of natural images can only be decoded using nonlinear techniques, while low-pass features can be extracted equally well by linear and nonlinear methods. Together, these results advance the state of the art in decoding natural stimuli from large populations of neurons.Author summaryNeural decoding is a fundamental problem in computational and statistical neuroscience. There is an enormous literature on this problem, applied to a wide variety of brain areas and nervous systems. Here we focus on the problem of decoding visual information from the retina. The bulk of previous work here has focused on simple linear decoders, applied to modest numbers of simultaneously recorded cells, to decode artificial stimuli. In contrast, here we develop a scalable nonlinear decoding method to decode natural images from the responses of over a thousand simultaneously recorded units, and show that this decoder significantly improves on the state of the art.

scholarly journals Targeting the vascular-specific phosphatase PTPRB protects against retinal ganglion cell loss in a pre-clinical model of glaucoma

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Benjamin R Thomson ◽  
Isabel A Carota ◽  
Tomokazu Souma ◽  
Saily Soman ◽  
Dietmar Vestweber ◽  
...  
Keyword(s):  
Aqueous Humor ◽  
Ganglion Cells ◽  
Cell Loss ◽  
Congenital Glaucoma ◽  
Retinal Ganglion ◽  
Loss Of Function ◽  
Gene Encoding ◽  
Clinical Model ◽  
Aqueous Humor Outflow ◽  
Novel Approach

Elevated intraocular pressure (IOP) due to insufficient aqueous humor outflow through the trabecular meshwork and Schlemm’s canal (SC) is the most important risk factor for glaucoma, a leading cause of blindness worldwide. We previously reported loss of function mutations in the receptor tyrosine kinase TEK or its ligand ANGPT1 cause primary congenital glaucoma in humans and mice due to failure of SC development. Here, we describe a novel approach to enhance canal formation in these animals by deleting a single allele of the gene encoding the phosphatase PTPRB during development. Compared to Tek haploinsufficient mice, which exhibit elevated IOP and loss of retinal ganglion cells, Tek+/-;Ptprb+/- mice have elevated TEK phosphorylation, which allows normal SC development and prevents ocular hypertension and RGC loss. These studies provide evidence that PTPRB is an important regulator of TEK signaling in the aqueous humor outflow pathway and identify a new therapeutic target for treatment of glaucoma.

scholarly journals Electrical match between initial segment and somatodendritic compartment for action potential backpropagation in retinal ganglion cells

2021 ◽  
Author(s):  
Sarah Goethals ◽  
Martijn Christiaan Sierksma ◽  
Xavier Nicol ◽  
Annabelle Reaux-Le Goazigo ◽  
Romain Brette
Keyword(s):  
Action Potential ◽  
Retinal Ganglion Cells ◽  
Initial Segment ◽  
Ganglion Cells ◽  
Axial Current ◽  
Retinal Ganglion ◽  
Channel Inactivation ◽  
Sodium Channel Inactivation ◽  
A Charge ◽  
Post Hoc

The action potential of most vertebrate neurons initiates in the axon initial segment (AIS), and is then transmitted to the soma where it is regenerated by somatodendritic sodium channels. For successful transmission, the AIS must produce a strong axial current, so as to depolarize the soma to the threshold for somatic regeneration. Theoretically, this axial current depends on AIS geometry and Na+ conductance density. We measured the axial current of mouse retinal ganglion cells using whole-cell recordings with post-hoc AIS labeling. We found that this current is large, implying high Na+ conductance density, and carries a charge that co-varies with capacitance so as to depolarize the soma by ~30 mV. Additionally, we observed that the axial current attenuates strongly with depolarization, consistent with sodium channel inactivation, but temporally broadens so as to preserve the transmitted charge. Thus, the AIS appears to be organized so as to reliably backpropagate the axonal action potential.

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