Biology subjects

Idrees, S.

Publications and source records attributed to Idrees, S..

7 recordsLinked to original sources

bioRxiv2026

Designing stimuli for non-invasive, cell-type-specific manipulation of retinal ganglion cell activity

The retina encodes visual information through parallel pathways formed by distinct retinal ganglion (RGC) types. Current understanding of how each cell type contributes to downstream visual processing and perception is limited by a lack of tools for selectively manipulating the activities of individual RGC types. Here, we introduce a computational framework called STORM (SpatioTemporal Orthogonal Response Modulation) that creates visual stimuli that aim to selectively modulate the activities of specific RGC types while minimally affecting the activities of nearby RGCs of non-targeted types. To illustrate the approach, demonstrate its flexibility, and identify conditions under which each simulated RGC type could be selectively manipulated, we first applied this framework to simplified models of RGC function, such as Linear-Nonlinear-Poisson (LNP) and LN-LN cascade models. We also deployed this approach on more complex (and more accurate) models of RGC responses, based on convolutional neural networks. We demonstrate that differences in spatial receptive fields, temporal dynamics, response polarities, and nonlinearities can provide sufficient degrees of freedom for designing stimuli that selectively manipulate individual RGC types. We also generalize this approach to conditions where the receptive field locations are unknown for in vivo and clinical applications.

neuroscience↗

bioRxiv2023

Fecal microbial transfer and complex carbohydrates mediate protection against COPD

ObjectiveChronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear. DesignUsing an in vivo mouse model of cigarette smoke-induced COPD and fecal microbial transfer (FMT), we characterized the fecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology, and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in sixteen COPD patients using a randomized, double-blind, placebo-controlled pilot study of inulin supplementation. ResultsFMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastrointestinal pathology and systemic immune changes. Protective effects were additive to smoking cessation. Disease features correlated with the relative abundance of Muribaculaceae, Desulfovibrionaceae and Lachnospiraceae family members. Proteomics and metabolomics identified downregulation of glucose and starch metabolism in cigarette smoke-associated microbiota, and supplementation of mice or human patients with complex carbohydrates improved disease outcomes. ConclusionThe gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically. What is already known on this topicO_LIChanges in gut microbiota are associated with COPD but the underlying host and microbial mechanisms are unclear, limiting the therapeutic applications. C_LI What this study addsO_LIMicrobiome composition and metabolism is reproducibly correlated with lung and gastrointestinal pathology in experimental COPD. C_LIO_LIMicrobiome modifying interventions effectively alleviate disease, including protective effects supplementing smoking cessation. C_LIO_LINutritional interventions targeting the microbiome in COPD patients demonstrate efficacy in a small pilot study. C_LI How this study might affect research, practice or policyO_LIMicrobiome-targeting therapeutics and nutritional interventions may be developed for COPD, including as supplements to smoking cessation. C_LI

physiology↗

bioRxiv2023

Biophysical neural adaptation mechanisms enable deep learning models to capture dynamic retinal computation

Adaptation is a universal aspect of neural systems that changes circuit computations to match prevailing inputs. These changes facilitate efficient encoding of sensory inputs while avoiding saturation. Conventional artificial neural networks (ANNs) have limited adaptive capabilities, hindering their ability to reliably predict neural output under dynamic input conditions. Can embedding neural adaptive mechanisms in ANNs improve their performance? To answer this question, we develop a new deep learning model of the retina that incorporates the biophysics of photoreceptor adaptation at the front-end of conventional convolutional neural networks (CNNs). These conventional CNNs build on Deep Retina, a previously developed model of retinal ganglion cell (RGC) activity. CNNs that include this new photoreceptor layer outperform conventional CNN models at predicting primate and rat RGC responses to naturalistic stimuli that include dynamic local intensity changes and large changes in the ambient illumination. These improved predictions result directly from adaptation within the phototransduction cascade. This research underscores the potential of embedding models of neural adaptation in ANNs and using them to determine how neural circuits manage the complexities of encoding natural inputs that are dynamic and span a large range of light levels.

neuroscience↗

bioRxiv2020

Dependence of perceptual saccadic suppression on peri-saccadic image flow properties and luminance contrast polarity

Across saccades, perceptual detectability of brief visual stimuli is strongly diminished. We recently observed that this perceptual suppression phenomenon is jumpstarted in the retina, suggesting that the phenomenon might be significantly more visual in nature than normally acknowledged. Here, we explicitly compared saccadic suppression strength when saccades were made across a uniform image of constant luminance versus when saccades were made across image patches of different luminance, width, and trans-saccadic luminance polarity. We measured perceptual contrast thresholds of human subjects for brief peri-saccadic flashes of positive (luminance increments) or negative (luminance decrements) polarity. Perceptual thresholds were >6-7 times higher when saccades translated a luminance stripe or edge across the retina than when saccades were made over a completely uniform image patch. Critically, both background luminance and flash luminance polarity relative to the background strongly modulated peri-saccadic contrast thresholds. In addition, all of these very same visual dependencies also occurred in the absence of any saccades, but with qualitatively similar rapid translations of image patches across the retina. Our results support the notion that perceptual saccadic suppression may be fundamentally a visual phenomenon, and they motivate neurophysiological and theoretical investigations on the role of saccadic eye movement commands in modulating its properties.

neuroscience↗

bioRxiv2020

Different contrast encoding in ON and OFF visual pathways

Subjective visual experience builds on sensory encoding of light reflected by different objects in our environment. Most retinal ganglion cells encode changes in light intensity, quantified as contrast, rather than the absolute intensity. Mathematically, contrast is often defined as a relative change in light intensity. Activity in the visual system and perceptual responses are usually explained with such definitions of contrast. Here, for the first time, we explicitly explored how contrast is actually represented in the visual system. Using mouse retina electrophysiology, we show that response strength of OFF retinal ganglion cells does not represent relative, but absolute changes in light intensity. ON RGC response strength is governed by a combination of absolute and relative change in light intensity. This is true for a wide range of ambient light levels, at least from scotopic to high mesopic regimes. Consequently, light decrements and increments are represented asymmetrically in the retina, which may explain the asymmetries in responses to negative and positive contrast observed throughout the visual system. These findings may help to more thoroughly design and interpret vision science studies where responses are driven by contrast of the visual stimuli.

neuroscience↗

bioRxiv2020

Retinal mechanisms of saccadic suppression and their role in processing sequential stimuli

Visual perception remains stable across saccadic eye movements, despite the concurrent strongly disruptive visual flow. This stability is partially associated with a reduction in visual sensitivity, known as saccadic suppression, which already starts in the retina with reduced ganglion cell sensitivity. However, the retinal circuit mechanisms giving rise to such suppression remain unknown. Here, we describe these mechanisms using electrophysiology in mouse, pig, and macaque retina, 2-photon calcium imaging, computational modeling, and human psychophysics. We find that sequential stimuli, such as those that naturally occur during saccades, trigger three independent suppressive mechanisms in the retina. The main suppressive mechanism is triggered by contrast-reversing sequential stimuli and originates within the receptive field center of ganglion cells. It does not involve inhibition or other known suppressive mechanisms such as saturation or adaptation. Instead, it relies on temporal filtering of the inherently slow response of cone photoreceptors coupled with downstream nonlinearities. Two further mechanisms of suppression are present predominantly in ON ganglion cells and originate in the receptive field surround, highlighting a novel disparity between ON and OFF ganglion cells. The mechanisms uncovered here likely play a role in shaping the retinal output following eye movements and other natural viewing conditions where sequential stimulation is ubiquitous.

neuroscience↗

bioRxiv2019

Saccadic suppression by way of retinal-circuit image processing

Visual sensitivity, probed through perceptual detectability of very brief visual stimuli, is strongly impaired around the time of rapid eye movements. This robust perceptual phenomenon, called saccadic suppression, is frequently attributed to active suppressive signals that are directly derived from eye movement commands. Here we show instead that visual-only mechanisms, activated by saccade-induced image shifts, can account for all perceptual properties of saccadic suppression that we have investigated. Such mechanisms start at, but are not necessarily exclusive to, the very first stage of visual processing in the brain, the retina. Critically, neural suppression originating in the retina outlasts perceptual suppression around the time of saccades, suggesting that extra-retinal movement-related signals, rather than causing suppression, may instead act to shorten it. Our results demonstrate a far-reaching contribution of visual processing mechanisms to perceptual saccadic suppression, starting in the retina, without the need to invoke explicit motor-based suppression commands.

neuroscience↗