Biology subjects

Marre, O.

Publications and source records attributed to Marre, O..

At least 19 recordsLinked to original sources

bioRxiv2026

Gamma-frequency firing persistently enhances intrinsic excitability in retinal ganglion cells

Experience-dependent plasticity is usually attributed to synaptic changes, but neuronal output also depends on changes in intrinsic excitability. Whether intrinsic excitability is persistently modified at the retinal output stage is unknown. Using whole-cell recordings from retinal ganglion cells (RGCs) of juvenile rats, we found that 40-Hz firing produced sustained potentiation of intrinsic excitability in low-input-resistance A-type RGCs and rapid potentiation of intrinsic excitability in high-input-resistance B-type RGCs. In A-type bursting RGCs, long-term potentiation of intrinsic excitability (LTP-IE) required Cav1 calcium channels for its induction. LTP-IE was associated with hyperpolarization of spike threshold and reduction of spike time jitter, due to reduced Kv1 potassium-family channel function. Potentiation also increased the probability that visually-evoked synaptic events triggered action potentials. Patterned firing therefore persistently reconfigures RGC input-output transformation through the Cav1-dependent regulation of Kv1 channels, revealing intrinsic plasticity at the retinal output stage.

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bioRxiv2026

Predicting the Efficacy of Myopia Control Spectacle Lenses by Simulating Their Optical Effect on the Retina

Slowing myopia progression is central to addressing a growing public health concern. Myopia control spectacle lenses with diverse optical designs have been proposed for this purpose, and show varying degrees of clinical efficacy. Relating their design to their efficacy remains an open challenge. Here we show that it is possible to predict their clinical efficacy from their optical design, by reconstructing their impact on the retinal image. We simulated how several lens designs affect the retinal image using a combined lens and eye optical model. By assuming that the retina extracts specific features from the retinal image to modulate eye growth, we could predict the cumulative absolute reduction in axial elongation (CARE) of lens designs with very different rationales and microstructures. Our results show that different myopia control spectacle lenses can be compared on a common optical basis, and that their efficacy is predictable from their optical properties. This work paves the way for rational design of next-generation lenses and for adapting designs to each patient's ocular optics.

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bioRxiv2026

Retinal adaptive mechanisms confer selectivity to homogeneous objects in natural scenes

Adaptive mechanisms in sensory neurons are crucial to transmit information in different contexts. In the retina, it is assumed that their role is to normalize neuronal responses to input statistics like mean and variance. However, this role has mostly been characterized with simple, artificial stimuli, and remains unclear for natural stimuli. Here we show that during their response to natural scenes, adaptive mechanisms reshape the feature selectivity of ganglion cells, the retinal output. We recorded retinal ganglion cell responses to rapid sequences of natural images in mice. Including a bio-inspired adaptive mechanism in an artificial neural network model was necessary to predict cell responses to new sequences of natural images. This adaptive mechanism tuned specific cell types to selectively respond to homogeneous regions situated within cluttered visual surrounds, a feature suited for detecting threats. Adaptive mechanisms do not merely normalize responses but actively enable new feature selectivity in the early visual system.

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bioRxiv2026

The extreme diversity of retinal amacrine cells has deep evolutionary roots

Amacrine cells (ACs) comprise a heterogeneous class of inhibitory neurons in the vertebrate retina, exhibiting morphological and functional complexity rivaling that of cortical interneurons. Here, we integrate single-cell and single-nucleus transcriptomic atlases from 24 vertebrate species to reconstruct the evolutionary origins of this extreme diversity. We identify 42 orthologous AC types (oACs), most of which exhibit a one-to-one correspondence across amniotes and, in many cases, across vertebrates. While core molecular identities are conserved, AC types vary in abundance and gene expression across species, likely reflecting adaptations to distinct visual ecologies. AC diversity scales with that of retinal ganglion cells (RGCs), indicative of co-evolution. Finally, we suggest that ACs arose from an AC-RGC hybrid precursor, with glycinergic ACs diverging early in vertebrate evolution, followed by a bifurcation between RGCs and GABAergic ACs. Together, these findings establish a unified evolutionary framework for understanding the diversity, development, and function of a class of inhibitory neurons across vertebrates.

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bioRxiv2026

VIP+ amacrine cells synchronize neural activity in the retina

In early sensory circuits, inhibitory interneurons are best known for mediating lateral inhibition, gain control, and feature selectivity, but their roles at the population level are less understood. Using two-photon digital holography, we found that in the retina, vasoactive intestinal peptide-expressing (VIP+) amacrine cells not only inhibit some retinal ganglion cell types via GABAergic synapses but also excite specific other types through gap junctions. Selective knockout of these junctions abolished synchronized firing among these ganglion cells, showing that VIP+ amacrine cells coordinate their activity. Thus, VIP+ interneurons have a dual, cell-type-specific role: synchronizing some ganglion cells electrically while inhibiting others chemically, thereby differentially shaping retinal output.

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bioRxiv2026

Optimality with room to vary: stiff and sloppy modes in a sensory population

Populations of sensory neurons are thought to be shaped by selective pressures for optimal information transmission, yet real neural circuits display substantial variability across stimulus repeats, across time, and between individuals. Reconciling this variability with normative theories requires understanding not only the optimal code, but also how performance changes under perturbations of that code. Here we analyze large-scale recordings from retinal ganglion cells responding to diverse naturalistic movies and spatial noise. We fit low-rank Ising models, recast as interpretable latent variable models, revealing that retinal population activity is well described by a small number of collective modes tightly coupled to the visual stimulus. The spatial receptive fields of the leading latent variables closely align with the principal components of masked natural images, consistent with efficient coding. Perturbation analyses based on the Hessian of the efficient coding objective show that this agreement is concentrated along stiff directions, where small deviations strongly degrade performance, whereas sloppy directions tolerate large variability. Across stimulus ensembles, the same stiff latent modes form a stable backbone of population interactions that generalizes between scenes and supports both efficient stimulus reconstruction and predictive coding of future inputs. These results show how sensitivity to perturbations structures sensory population codes, allowing normative optimality to coexist with rich variability.

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bioRxiv2026

Primitives for motion segmentation in the retina

The center surround structure of ganglion cells receptive fields is suited for edge detection, a first step towards image segmentation. However, in a dynamical visual scene with moving, textured objects, it is less clear how the retina represents the local boundaries of these objects. Here, we show that the spatial selectivity of ganglion cells changes during their responses to a moving object. Specific cell types only respond to contrast changes near the edges of the moving object, while being insensitive to changes in other parts of their receptive field. Using a non-linear model to reproduce this result, we could isolate the mechanism responsible for this selective representation. These types of ganglion cells represent selectively textures only when they are near moving edges, and may thus provide useful primitives for motion segmentation.

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bioRxiv2025

The Rod Bipolar Cell Pathway Contributes To Surround Responses In OFFRetinal Ganglion Cells

Sensory neurons can be influenced by stimuli beyond their receptive field center, yet the mechanisms underlying this surround modulation remain poorly understood. In the retina, many OFF ganglion cells exhibit responses to ON stimulation outside their receptive field center. However, disentangling the pathways and cell types contributing to these responses has been challenging with traditional experimental approaches. Here, we combined optogenetics, two-photon holographic stimulation, and multi-electrode array recordings to identify the intermediate retinal cell types involved in this circuit. We found that the pathway formed by rod bipolar cells and AII amacrine cells--one of the primary relays of rod-driven signals under low-light conditions--plays a key role in mediating this surround modulation. Specifically, crossover inhibition exploits the same amacrine cells responsible for surround suppression to disinhibit distant ganglion cells. This suggests that the retina repurposes existing circuits for surround modulation, optimizing resources through multifunctional inhibitory pathways.

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bioRxiv2025

Increased sensitivity to myopia and altered retinal ON/OFF balance in a mouse model lacking Dusp4

Myopia, influenced by environmental and genetic factors, occurs when the emmetropization process fails to stop, causing excessive eyeball growth. Highly myopic animal models lacking a functional ON-pathway identified Dusp4 as a potential gene implicated in myopia. Here, we used a mouse model lacking DUSP4 to gain a better understanding of its retinal role and the mechanisms implicated in myopia development. Dusp4-/- mice have a reduced basal level of retinal dopamine and a higher susceptibility to lens-induced myopia. Dusp4 is expressed in ON-bipolar cells and a subset of OFF-bipolar cells in a light dependent manner. The absence of DUSP4 causes a hyperactivation of the MAPK/ERK pathway. Dusp4-/- mice showed reduced optomotor responses, increased ON-bipolar cell depolarization, reduced oscillatory potentials together with altered OFF and ON-OFF RGC responses to light flashes. These data provide insights into retina-driven mechanisms of myopization, nuancing the impact of ON and OFF pathways upon emmetropization.

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bioRxiv2025

Discovering flexible codes for prediction across timescales in the retina

The retina must encode visual information in a way that supports fast, predictive behavior despite significant processing delays. How this encoding adapts in an ever-changing world, when the temporal statistics of visual input shift, remains an open question. Here we record from populations of retinal ganglion cells in the axolotl as they respond to a stochastic moving bar stimulus across five different temporal correlation scales. Using the information bottleneck (IB) framework, and treating the prediction horizon as a free parameter inferred from the data, we ask what timescale of future motion the retina is optimized to predict under each stimulus condition. We find that the retina adapts its predictive encoding to the changing stimulus statistics: as the time constant of the stimulus dynamics increases, the inferred prediction horizon lengthens. The population shifts toward encoding more velocity information, and motion anticipation grows, all the while maintaining near-optimal prediction efficiency. Population surprise, quantified through a Boltzmann machine model of the retinal response distribution, tracks stimulus surprise under the inferred optimal compression. This connects the retinas reversal response to efficient predictive encoding. These results show that retinal population codes flexibly adjust their predictive timescale to the temporal structure of their inputs. More broadly, they demonstrate that the IB framework can be used to discover, not just test for, computational objectives in sensory populations.

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bioRxiv2025

Ectopic expression of two cone opsins in mouse RGCs results in opposite responses to light stimulation, likely due to differential G protein activation

Retinitis pigmentosa, a leading cause of inherited blindness, results in photoreceptor degeneration that current optogenetic approaches aim to address through microbial opsin expression in retinal ganglion cells (RGCs). While these microbial proteins restore light sensitivity, their clinical potential remains limited by low light sensitivity and immunogenicity risks. Recent efforts have focused on vertebrate opsins as safer alternatives, with mid-wavelength cone opsin (MW-opsin) demonstrating RGC depolarization via endogenous G-protein signaling. In this study, we reveal a surprising divergence in signaling outcomes of expressing short-wavelength mouse cone opsin (Opn1sw) in RGCs of blind mice. Using multielectrode array recordings and whole-cell patch clamping, we demonstrate that Opn1sw induces membrane hyperpolarization in RGCs - a stark contrast to MW-opsins depolarizing effects. This unexpected inversion suggests differential engagement of intracellular signaling pathways, potentially stemming from distinct G-protein coupling preferences. Comparative analysis of native G-protein expression profiles in RGCs versus cone photoreceptors supports this hypothesis, revealing mismatches that may explain ectopic opsin behavior. Our findings challenge the assumption of conserved opsin signaling across spectral subtypes and cell types, highlighting critical gaps in understanding vertebrate opsin-G protein interactions in non-native cellular environments. This discovery points to the necessity of systematic characterization of opsin signaling networks in target retinal cells, a prerequisite for engineering optimized optogenetic tools that reliably produce desired electrophysiological outcomes. By establishing spectral subtype-dependent signaling divergence, our work redefines parameters for developing next-generation vision restoration therapies.

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bioRxiv2025

Direction-selective retinal ganglion cells encode motion direction uniformly, despite having discretely distributed cardinal preferences

On-Off direction-selective retinal ganglion cells (DS RGCs) exhibit broad tuning curves, responding robustly to motion aligned with or near their preferred direction. These cells comprise four major subtypes, each tuned to motion along one of the four cardinal axes: nasal, superior, temporal, or inferior. However, natural stimuli can move in any direction, and it remains unclear whether intermediate directions are encoded less effectively, or whether this cardinal organization nevertheless supports uniform direction encoding. Here, we combined previous electrophysiological recordings with an information-theoretic measure, the Stimulus Specific Information, to estimate the directional sensitivity of small populations of recorded neurons. This analysis revealed that DS RGC populations are uniformly sensitive across all directions of motion. We then asked whether the observed homogeneous sensitivity was a consequence of DS RGCs maximizing the average stimulus information. Simulations with artificially modified tuning curve widths revealed that DS cells prioritize avoiding pronounced drops in sensitivity over maximizing the average transmitted Information. Maximizing this minimal sensitivity may therefore be a principle to understand the organization of sensory systems.

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bioRxiv2025

Preserving predictive information under biologically plausible compression

Retinal ganglion cells (RGCs) show high convergence onto their downstream projections, which poses a problem for information transfer: how can information be preserved through a synaptic layer that has significantly more inputs than outputs? Lossy compression suggests many efficient, yet computation-agnostic, methods for reading out input stimuli or activity patterns. Focusing on prediction as a ubiquitous computation in the brain, we compare compressions that explicitly retain predictive information to common neural compression frameworks that do not. We find evidence that downstream areas may compress their retinal inputs in a way that allows them to perform optimal predictive computations across many natural scenes. Other sensory systems also exhibit compression in their processing hierarchies, such as at the glomeruli stage in the olfactory system, and we hope that our framework will be useful in cases where it is not yet known how information about a specific computation is maintained under compression. SIGNIFICANCE STATEMENTProducing successful behavior, such as escaping predators, requires the visual system to overcome significant sensory processing delays by predicting the future state of the world. Neurons in the eye capture some of the most predictive features of visual information, but this information must be accessible to downstream areas that receive synaptically compressed inputs from the retina. We tested how carefully retinal activity must be compressed to preserve predictive information in natural scenes. Biologically plausible compressions that are agnostic to prediction can preserve substantial future information, but only compression optimized for this task extracts generalizable motifs that allow it to predict in any natural scene. This suggests that downstream circuits may optimally compress their inputs specifically for the task of prediction.

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bioRxiv2024

Strong, but not weak, noise correlations are beneficial for population coding

Neural correlations play a critical role in sensory information coding. They are of two kinds: signal correlations, when neurons have overlapping sensitivities, and noise correlations from network effects and shared noise. It is commonly thought that stimulus and noise correlations should have opposite signs to improve coding. However, experiments from early sensory systems and cortex typically show the opposite effect, with many pairs of neurons showing both types of correlations to be positive and large. Here, we develop a theory of information coding by correlated neurons which resolves this paradox. We show that noise correlations are always beneficial if they are strong enough. Extensive tests on retinal recordings under different visual stimuli confirm our predictions. Finally, using neuronal recordings and modeling, we show that for high dimensional stimuli noise correlation benefits the encoding of fine-grained details of visual stimuli, at the expense of large-scale features, which are already well encoded.

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bioRxiv2024

Nonlinear spatial integration allows the retina to detect the sign of defocus in natural scenes

Eye growth is regulated by the visual input. Many studies suggest that the retina can detect if a visual image is focused in front or behind the back of the eye, and modulate eye growth to bring it back to focus. How can the retina distinguish between these two types of defocus? Here we simulated how eye optics transform natural images and recorded how the isolated retina responds to different types of simulated defocus. We found that some ganglion cell types could distinguish between an image focussed in front or behind the retina, by estimating spatial contrast. Aberrations in the eye optics made spatial contrast, but not luminance, a reliable cue to distinguish these two types of defocus. Our results suggest a mechanism for how the retina can estimate the sign of defocus and provide an explanation for several results aiming at mitigating strong myopia by slowing down eye growth.

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bioRxiv2023

Nitric oxide mediates differential effects in mouse retinal ganglion cells

Neuromodulators have major influences on the regulation of neural circuit activity across the nervous system. Nitric oxide (NO) has been shown to be a prominent neuromodulator in many circuits and has been extensively studied in the retina. Here, it has been associated with the regulation of light adaptation, gain control, and gap junctional coupling, but its effect on the retinal output, specifically on the different types of retinal ganglion cells (RGCs), is still poorly understood. In this study, we used two-photon Ca2+imaging and multi-electrode array (MEA) recordings to measure light-evoked activity of RGCs in the ganglion cell layer in the ex vivo mouse retina. This approach allowed us to investigate the neuromodulatory effects of NO on a cell type-level. Our findings reveal that NO selectively modulates the suppression of temporal responses in a distinct subset of contrast-suppressed RGC types, increasing their activity without altering the spatial properties of their receptive fields. Given that under photopic conditions, NO release is triggered by quick changes in light levels, we propose that these RGC types signal fast contrast changes to higher visual regions. Remarkably, we found that about one-third of the RGC types, recorded using two-photon Ca2+imaging, exhibited consistent, cell type-specific adaptational response changes throughout an experiment, independent of NO. By employing a sequential-recording paradigm, we could disentangle those additional adaptational response changes from drug-induced modulations. Taken together, our research highlights the selective neuromodulatory effects of NO on RGCs and emphasizes the need of considering non-pharmacological activity changes, like adaptation, in such study designs.

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bioRxiv2023

Stimulus invariant aspects of the retinal code drive discriminability of natural scenes

Everything that the brain sees must first be encoded by the retina, which maintains a reliable representation of the visual world in many different, complex natural scenes while also adapting to stimulus changes. This study quantifies whether and how the brain selectively encodes stimulus features about scene identity in complex naturalistic environments. While a wealth of previous work has dug into the static and dynamic features of the population code in retinal ganglion cells, less is known about how populations form both flexible and reliable encoding in natural moving scenes. We record from the larval salamander retina responding to five different natural movies, over many repeats, and use these data to characterize the population code in terms of single-cell fluctuations in rate and pairwise couplings between cells. Decomposing the population code into independent and cell-cell interactions reveals how broad scene structure is encoded in the retinal output. while the single-cell activity adapts to different stimuli, the population structure captured in the sparse, strong couplings is consistent across natural movies as well as synthetic stimuli. We show that these interactions contribute to encoding scene identity. We also demonstrate that this structure likely arises in part from shared bipolar cell input as well as from gap junctions between retinal ganglion cells and amacrine cells.

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bioRxiv2023

Temporal pattern recognition in retinal ganglion cells is mediated by dynamical inhibitory synapses

A fundamental task for the brain is to generate predictions of future sensory inputs, and signal errors in these predictions. Many neurons have been shown to signal omitted stimuli during periodic stimulation, even in the retina. However, the mechanisms of this error signaling are unclear. Here we show that depressing inhibitory synapses enable the retina to signal an omitted stimulus in a flash sequence. While ganglion cells, the retinal output, responded to an omitted flash with a constant latency over many frequencies of the flash sequence, we found that this was not the case once inhibition was blocked. We built a simple circuit model and showed that depressing inhibitory synapses were a necessary component to reproduce our experimental findings. We also generated new predictions with this model, that we confirmed experimentally. Depressing inhibitory synapses could thus be a key component to generate the predictive responses observed in many brain areas.

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