Paradoxical Rules of Spike Train Decoding Revealed at the Sensitivity Limit of Vision

Smeds, Lina; Takeshita, Daisuke; Turunen, Tuomas; Tiihonen, Jussi; Westö, Johan; Martyniuk, Nataliia; Seppänen, Aarni; Ala-Laurila, Petri

doi:10.1016/j.neuron.2019.08.005

Cited by 44 publications

(122 citation statements)

References 54 publications

(74 reference statements)

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“…Several studies showed that the brain might not be able to make the best use of all the signals coming from the different cell types [28,29]. However, recent works (see, for example, [30]) have shown that neurons might integrate the output of several cell types together, as early as in the LGN.…”

Section: Limits Of the Ideal Observer Analysismentioning

confidence: 99%

Towards optogenetic vision restoration with high resolution

et al. 2020

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In many cases of inherited retinal degenerations, ganglion cells are spared despite photoreceptor cell death, making it possible to stimulate them to restore visual function. Several studies have shown that it is possible to express an optogenetic protein in ganglion cells and make them light sensitive, a promising strategy to restore vision. However the spatial resolution of optogenetically-reactivated retinas has rarely been measured, especially in the primate. Since the optogenetic protein is also expressed in axons, it is unclear if these neurons will only be sensitive to the stimulation of a small region covering their somas and dendrites, or if they will also respond to any stimulation overlapping with their axon, dramatically impairing spatial resolution. Here we recorded responses of mouse and macaque retinas to random checkerboard patterns following an in vivo optogenetic therapy. We show that optogenetically activated ganglion cells are each sensitive to a small region of visual space. A simple model based on this small receptive field predicted accurately their responses to complex stimuli. From this model, we simulated how the entire population of light sensitive ganglion cells would respond to letters of different sizes. We then estimated the maximal acuity expected by a patient, assuming it could make an optimal use of the information delivered by this reactivated retina. The obtained acuity is above the limit of legal blindness. Our model also makes interesting predictions on how acuity might vary upon changing the therapeutic strategy, assuming an optimal use of the information present in the retinal activity. Optogenetic therapy could thus potentially lead to high resolution vision, under conditions that our model helps to determinine.

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Section: Limits Of the Ideal Observer Analysismentioning

confidence: 99%

Towards optogenetic vision restoration with high resolution

et al. 2020

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“…We did so by creating a movie ( Supplementary Movie 2) where we applied a sinusoidal change to individual shape parameters in equation 3. In this way, at any given time and for the ℎ eigenpose, the mouse body could be described as ( ) = ̅ + √6sin (2 ) • . By looking at the movie it is apparent that each eigenpose captures coordinated changes in the distances between body landmarks and angles between head and body.…”

Section: Interpretation Of the Eigenposesmentioning

confidence: 99%

“…For this analysis the response matrix encompassed an epoch starting 0.33s before the stimulus onset and ending 2s after the onset. Since both the number of clusters and the duration of the primitive was unknown we repeated the clustering for a range of [2,10] clusters and for six different durations (0.133s, 0.2s, 0.333s, 0.4s, 0.666s and 1s). In order to model arbitrarily (finite) long ` temporal relations between subsequent primitives occurring on the same trial we used Variable-order Markov Models (VMMs, [62,63]).…”

Section: Analysis Of Behavioural Primitivesmentioning

confidence: 99%

“…Mice are innately able to respond to changes in their sensory landscape by producing sequences of actions aimed at maximizing their welfare and chances for survival. Such spontaneous behaviors as exploration [1,2], hunting [3,4], and escape and freeze [5][6][7][8], while heterogeneous, share the key property that they can be reproducibly elicited in the lab by controlled sensory stimulation. The ability of sensory stimuli to evoke a reproducible behavioural response in these paradigms makes them an important experimental tool to understand how inputs are encoded and interpreted in the brain, and appropriate actions selected [5,[8][9][10].…”

Section: Introductionmentioning

confidence: 99%

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A high dimensional quantification of mouse defensive behaviours reveals enhanced diversity and stimulus specificity

Storchi¹,

Milosavljevic²,

Allen³

et al. 2020

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The ability of specific sensory stimuli to evoke spontaneous behavioural responses in the mouse represents a powerful approach to study how the mammalian brain processes sensory information and selects appropriate motor actions. For visually and auditory guided behaviours the relevant action has been empirically identified as a change in locomotion state. However, the extent to which locomotion alone captures the diversity of those behaviours and their sensory specificity is unknown.To tackle this problem we developed a method to obtain a faithful 3D reconstruction of the mouse body that enabled us to quantify a wide variety of movements and changes in postures. This higher dimensional description of behaviour revealed that responses to different sensory inputs is more stimulus-specific than indicated by locomotion data alone. Thus, equivalent locomotion patterns evoked by different stimuli (e.g. looming and sound evoking locomotion arrest) could be well separated along other dimensions. The enhanced stimulus-specificity was explained by a surprising diversity of behavioural responses. A clustering analysis revealed that distinct combinations of motor actions and postures, giving rise to at least 7 different behaviours, were required to account for stimulus-specificity. Moreover, each stimulus evoked more than one behaviour revealing a robust one-to-many mapping between sensations and behaviours that could not be detected from locomotion data.Our results challenge the current view of visually and auditory guided behaviours as purely locomotion-based actions (e.g. freeze, escape) and indicate that behavioural diversity and sensory specificity unfold in a higher dimensional space spanning multiple motor actions. `

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“…Three GC types in the mouse retina receive input from the RB pathway at or near visual threshold: the ON α GC and the OFF α and δ GCs, which exhibit high sensitivity to spatial contrast in the visual scene—similar to primate parasol cells —and project to the geniculo-cortical pathway (Ala-Laurila et al, 2011; Ala-Laurila and Rieke, 2014; Dunn et al, 2006; Grimes et al, 2018a; Grimes et al, 2015; Grimes et al, 2014b; Grimes et al, 2018b; Ke et al, 2014; Kuo et al, 2016; Murphy and Rieke, 2006, 2008). Input from the RB pathway to ON α GCs provides the signal that guides behavior at visual threshold (Smeds et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Connectomic analysis reveals an interneuron with an integral role in the retinal circuit for night vision

Park

Lieberman

et al. 2020

Preprint

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18Blindness to Yale University. We thank Tim Maugel and the Laboratory for Biological 19 Ultrastructure (Department of Biology, UMD) for assistance with transmission electron 20 microscopy, Alexander Baden for assistance with 3D visualization, and Kacie Furcolo and Adit 21 Sabnis for assistance with SBEM dataset skeletonization. We thank Cole Graydon for 22 comments on the manuscript. 24 Summary 31The mammalian rod bipolar (RB) cell pathway is perhaps the best-studied circuit in the 32 vertebrate retina. Its synaptic interactions with other retinal circuits, however, remain 33 unresolved. Here, we combined anatomical and physiological analyses of the mouse retina to 34 discover that the majority of synaptic inhibition to the AII amacrine cell (AC), the central neuron 35 in the RB pathway, is provided by a single interneuron type: a multistratified, axon-bearing 36 GABAergic AC, with dendrites in both ON and OFF synaptic layers, but with a pure ON 37 (depolarizing) response to light. We used the nNOS-CreER mouse retina to confirm the identity 38 of this interneuron as the wide-field NOS-1 AC. Our study demonstrates generally that novel 39 neural circuits can be identified from targeted connectomic analyses and specifically that the 40 NOS-1 AC mediates long-range inhibition during night vision and is a major element of the RB 41 pathway. 42 43 74 remain. Most significantly, we do not know the identity of the spiking, GABAergic AC that drives 75 a receptive field surround in the AII during rod-mediated vision via synaptic inhibition of the AII 76 itself (Bloomfield and Xin, 2000); understanding mechanisms contributing to surround inhibition 77 4 is important because such inhibition tunes AII responses to spatial features of the visual 78 stimulus. 79Here, we identified the major inhibitory input to the AII by combining anatomical, genetic, 80 and electrophysiological analyses in a three-step process. One, we reconstructed ACs that 81 provided synaptic input to AIIs in a volume of mouse retina imaged by scanning block-face 82 electron microscopy [SBEM; (Denk and Horstmann, 2004)]. Two, we evaluated published 83 descriptions of reporter mouse lines to identify genetically-accessible ACs that had the 84 anatomical characteristics of the cells reconstructed from SBEM images. And three, we used 85 electrophysiological recordings and genetics-based circuit analysis to demonstrate that a 86 candidate AC, which provided the great majority of the inhibitory synaptic input to AIIs, exhibited 87 a light response predicted by its anatomy and made GABAergic synapses onto AIIs. This 88 spiking, GABAergic AC is a multistratified, ON AC denoted NOS-1 AC and identified in the 89 nNOS-CreER mouse (Zhu et al., 2014). We conclude that the NOS-1 AC is an integral 90 component of the RB pathway and a significant source of long-range inhibition during night 91 vision. More generally, our study demonstrates the utility of targeted, small-scale "connectomic" 92 analysis for identification of novel neural circuits. 94 Results 95AIIs in the ...

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Paradoxical Rules of Spike Train Decoding Revealed at the Sensitivity Limit of Vision

Cited by 44 publications

References 54 publications

Towards optogenetic vision restoration with high resolution

Towards optogenetic vision restoration with high resolution

A high dimensional quantification of mouse defensive behaviours reveals enhanced diversity and stimulus specificity

Connectomic analysis reveals an interneuron with an integral role in the retinal circuit for night vision

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