Biology subjects

Smith, M. A.

Publications and source records attributed to Smith, M. A..

At least 55 records · Page 3Linked to original sources

bioRxiv2020

Interplay between intraocular and intracranial pressure effects on the optic nerve head in vivo

Intracranial pressure (ICP) has been proposed to play an important role in the sensitivity to intraocular pressure (IOP) and susceptibility to glaucoma. However, the in vivo effects of simultaneous, controlled, acute variations in ICP and IOP have not been directly measured. We quantified the deformations of the anterior lamina cribrosa (ALC) and scleral canal at Bruchs membrane opening (BMO) under acute elevation of IOP and/or ICP. Four eyes of three monkeys were imaged in vivo with OCT under four pressure conditions: IOP and ICP either at baseline or elevated. The BMO and ALC were reconstructed from manual delineations. From these, we determined canal area at the BMO (BMO area), BMO aspect ratio and planarity, and ALC median depth relative to the BMO plane. To better account for the pressure effects on the imaging, we also measured ALC visibility as a percent of the BMO area. Further, ALC depths were analyzed only in regions where the ALC was visible in all pressure conditions. Bootstrap sampling was used to obtain mean estimates and confidence intervals, which were then used to test for significant effects of IOP and ICP, independently and in interaction. Response to pressure manipulation was highly individualized between eyes, with significant changes detected in a majority of the parameters. Significant interactions between ICP and IOP occurred in all measures, except ALC visibility. On average, ICP elevation expanded BMO area by 0.17mm2 at baseline IOP, and contracted BMO area by 0.02 mm2 at high IOP. ICP elevation decreased ALC depth by 10m at baseline IOP, but increased depth by 7 m at high IOP. ALC visibility decreased as ICP increased, both at baseline (-10%) and high IOP (-17%). IOP elevation expanded BMO area by 0.04 mm2 at baseline ICP, and contracted BMO area by 0.09 mm2 at high ICP. On average, IOP elevation caused the ALC to displace 3.3 m anteriorly at baseline ICP, and 22 m posteriorly at high ICP. ALC visibility improved as IOP increased, both at baseline (5%) and high ICP (8%). In summary, changing IOP or ICP significantly deformed both the scleral canal and the lamina of the monkey ONH, regardless of the other pressure level. There were significant interactions between the effects of IOP and those of ICP on LC depth, BMO area, aspect ratio and planarity. On most eyes, elevating both pressures by the same amount did not cancel out the effects. Altogether our results show that ICP affects sensitivity to IOP, and thus that it can potentially also affect susceptibility to glaucoma. Research Highlights- In vivo ONH deformations caused by acute, controlled, simultaneous changes in IOP and/or ICP can be directly visualized and measured in the monkey eye using OCT. - Acute changes of either IOP or ICP significantly deformed both the scleral canal and the lamina cribrosa, regardless of the other pressure level. - Pressures interacted, meaning that the effects of one pressure depended significantly on the level of the other pressure. - Elevating both pressures did not cancel out the effects of one of them being elevated. - Our results show that ICP affects sensitivity to IOP, and thus that it can potentially also affect susceptibility to glaucoma.

bioengineering↗

bioRxiv2020

Integrative genomics identifies lncRNA regulatory networks across 1,044 pediatric leukemias and solid tumors

Long non-coding RNAs (lncRNAs) play an important role in gene regulation and contribute to tumorigenesis. While pan-cancer studies of lncRNA expression have been performed for adult malignancies, the lncRNA landscape across pediatric cancers remains largely uncharted. Here, we curate RNA sequencing data for 1,044 pediatric leukemia and solid tumors and integrate paired tumor whole genome sequencing and epigenetic data in relevant cell line models to explore lncRNA expression, regulation, and association with cancer. We report a total of 2,657 robustly expressed lncRNAs across six pediatric cancers, including 1,142 exhibiting histotype-specific expression. DNA copy number alterations contributed to lncRNA dysregulation at a proportion comparable to protein coding genes. Application of a multi-dimensional framework to identify and prioritize lncRNAs impacting gene networks revealed that lncRNAs dysregulated in pediatric cancer are associated with proliferation, metabolism, and DNA damage hallmarks. Analysis of upstream regulation via cell-type specific transcription factors further implicated distinct histotype-specific and developmental lncRNAs. We integrated our analyses to prioritize lncRNAs for experimental validation and showed that silencing of TBX2-AS1, our top-prioritized neuroblastoma-specific lncRNA, resulted in significant growth inhibition of neuroblastoma cells, confirming our computational predictions. Taken together, these data provide a comprehensive characterization of lncRNA regulation and function in pediatric cancers and pave the way for future mechanistic studies.

cancer biology↗

bioRxiv2020

Bridging neuronal correlations and dimensionality reduction

Two commonly used approaches to study interactions among neurons are spike count correlation, which describes pairs of neurons, and dimensionality reduction, applied to a population of neurons. While both approaches have been used to study trial-to-trial correlated neuronal variability, they are often used in isolation and have not been directly related. We first established concrete mathematical and empirical relationships between pairwise correlation and metrics of population-wide covariability based on dimensionality reduction. Applying these insights to macaque V4 population recordings, we found that the previously reported decrease in mean pairwise correlation associated with attention stemmed from three distinct changes in population-wide covariability. Overall, our work builds the intuition and formalism to bridge between pairwise correlation and population-wide covariability and presents a cautionary tale about the inferences one can make about population activity by using a single statistic, whether it be mean pairwise correlation or dimensionality.

neuroscience↗

bioRxiv2020

The Effects of Strain and Estrous Cycle on Heroin- and Sucrose-Maintained Responding in Female Rats

Heroin intake decreases during the proestrus phase of the estrous cycle in female, Long-Evans rats. The purpose of this study was to (1) determine if proestrus-induced decreases in heroin intake extend across rat strains and (2) determine if proestrus-induced decreases in responding extend to a nondrug reinforcer. Female rats were implanted with intravenous catheters and trained to self-administer heroin. Estrous cycle was tracked daily for the duration of the study. During testing, Lewis, Sprague-Dawley, and Long Evans rats self-administered low (0.0025 mg/kg) and high (0.0075 mg /kg) doses of heroin (Experiment 1) and then self-administered sucrose (Experiment 2) on fixed ratio (FR1) schedules of reinforcement. Heroin intake decreased significantly during proestrus in all three rat strains under at least one dose condition; however, sucrose intake did not decrease during proestrus in any strain. These data indicate that responding maintained by heroin, but not a nondrug reinforcer, significantly decreases during proestrus in female rats and that these effects are consistent across rat strain.

animal behavior and cognition↗

bioRxiv2020

DNA methylation is required to maintain DNA replication timing precision and 3D genome integrity

DNA replication timing and three-dimensional (3D) genome organisation occur across large domains associated with distinct epigenome patterns to functionally compartmentalise genome regulation. However, it is still unclear if alternations in the epigenome, in particular cancer-related DNA hypomethylation, can directly result in alterations to cancer higher order genome architecture. Here, we use Hi-C and single cell Repli-Seq, in the colorectal cancer DNMT1 and DNMT3B DNA methyltransferases double knockout model, to determine the impact of DNA hypomethylation on replication timing and 3D genome organisation. First, we find that the hypomethylated cells show a striking loss of replication timing precision with gain of cell-to-cell replication timing heterogeneity and loss of 3D genome compartmentalisation. Second, hypomethylated regions that undergo a large change in replication timing also show loss of allelic replication timing, including at cancer-related genes. Finally, we observe the formation of broad ectopic H3K4me3-H3K9me3 domains across hypomethylated regions where late replication is maintained, that potentially prevent aberrant transcription and loss of genome organisation after DNA demethylation. Together, our results highlight a previously underappreciated role for DNA methylation in maintenance of 3D genome architecture.

molecular biology↗

bioRxiv2020

LY-CoV555, a rapidly isolated potent neutralizing antibody, provides protection in a non-human primate model of SARS-CoV-2 infection

SARS-CoV-2 poses a public health threat for which therapeutic agents are urgently needed. Herein, we report that high-throughput microfluidic screening of antigen-specific B-cells led to the identification of LY-CoV555, a potent anti-spike neutralizing antibody from a convalescent COVID-19 patient. Biochemical, structural, and functional characterization revealed high-affinity binding to the receptor-binding domain, ACE2 binding inhibition, and potent neutralizing activity. In a rhesus macaque challenge model, prophylaxis doses as low as 2.5 mg/kg reduced viral replication in the upper and lower respiratory tract. These data demonstrate that high-throughput screening can lead to the identification of a potent antiviral antibody that protects against SARS-CoV-2 infection. One Sentence SummaryLY-CoV555, an anti-spike antibody derived from a convalescent COVID-19 patient, potently neutralizes SARS-CoV-2 and protects the upper and lower airways of non-human primates against SARS-CoV-2 infection.

immunology↗

bioRxiv2020

EEG signals index a global signature of arousal embedded in neuronal population recordings

Electroencephalography (EEG) has long been used to index brain states, from early studies describing activity during visual stimulation to modern work employing complex perceptual tasks. These studies shed light on brain-wide signals but lacked explanatory power at the single neuron level. Similarly, single neuron studies can suffer from inability to measure brain-wide signals. Here, we combined these techniques while monkeys performed a change detection task and discovered a link between EEG and a signal embedded in spiking responses. This slow drift was associated with arousal: decreases in pre-stimulus power/increases in P1 amplitude were accompanied by :1) increases in pupil size, false alarm rate and saccade velocity; and 2) decreases in microsaccade rate and reaction time. These results show that brain-wide EEG signals can be used to index modes of activity acquired from direct neural recordings, that in turn reflect global changes in brain state that influence perception and behavior.

neuroscience↗

bioRxiv2020

The eyes reflect an internal cognitive state embedded in the population activity of cortical neurons

Decades of research have shown that global brain states such as arousal can be indexed by measuring the properties of the eyes. Neural signals from individual neurons, populations of neurons, and field potentials measured throughout much of the brain have been associated with the size of the pupil, small fixational eye movements, and vigor in saccadic eye movements. However, precisely because the eyes have been associated with modulation of neural activity across the brain, and many different kinds of measurements of the eyes have been made across studies, it has been difficult to clearly isolate how internal states affect the behavior of the eyes, and vice versa. Recent work in our laboratory identified a latent dimension of neural activity in macaque visual cortex on the timescale of minutes to tens of minutes. This slow drift was associated with perceptual performance on an orientation-change detection task, as well as neural activity in visual and prefrontal cortex (PFC), suggesting it might reflect a shift in a global brain state. This motivated us to ask if the neural signature of this internal state is correlated with the action of the eyes in different behavioral tasks. We recorded from visual cortex (V4) while monkeys performed a change detection task, and the prefrontal cortex, while they performed a memory-guided saccade task. On both tasks, slow drift was associated with a pattern that is indicative of changes in arousal level over time. When pupil size was large, and the subjects were in a heighted state of arousal, microsaccade rate and reaction time decreased while saccade velocity increased. These results show that the action of the eyes is associated with a dominant mode of neural activity that is pervasive and task-independent, and can be accessed in the population activity of neurons across the cortex.

neuroscience↗

bioRxiv2020

Mechanosensing through direct binding of tensed F-actin by LIM domains

Mechanical signals transmitted through the cytoplasmic actin cytoskeleton must be relayed to the nucleus to control gene expression. LIM domains are protein-protein interaction modules found in cytoskeletal proteins and transcriptional regulators; however, it is unclear if there is a direct link between these two functions. Here we identify three LIM protein families (zyxin, paxillin, and FHL) whose members preferentially localize to the actin cytoskeleton in mechanically-stimulated cells through their tandem LIM domains. A minimal actin-myosin reconstitution system reveals that representatives of all three families directly bind F-actin only in the presence of mechanical force. Point mutations at a site conserved in each LIM domain of these proteins selectively disrupt tensed F-actin binding in vitro and cytoskeletal localization in cells, demonstrating a common, avidity-based mechanism. Finally, we find that binding to tensed F-actin in the cytoplasm excludes the cancer-associated transcriptional co-activator FHL2 from the nucleus in stiff microenvironments. This establishes direct force-activated F-actin binding by FHL2 as a mechanosensing mechanism. Our studies suggest that force-dependent sequestration of LIM proteins on the actin cytoskeleton could be a general mechanism for controlling nuclear localization to effect mechanical signaling.

biophysics↗

bioRxiv2020

Slow drift of neural activity as a signature of impulsivity in macaque visual and prefrontal cortex

An animals decision depends not only on incoming sensory evidence but also on its fluctuating internal state. This internal state is a product of cognitive factors, such as fatigue, motivation, and arousal, but it is unclear how these factors influence the neural processes that encode the sensory stimulus and form a decision. We discovered that, over the timescale of tens of minutes during a perceptual decision-making task, animals slowly shifted their likelihood of reporting stimulus changes. They did this unprompted by task conditions. We recorded neural population activity from visual area V4 as well as prefrontal cortex, and found that the activity of both areas slowly drifted together with the behavioral fluctuations. We reasoned that such slow fluctuations in behavior could either be due to slow changes in how the sensory stimulus is processed or due to a process that acts independently of sensory processing. By analyzing the recorded activity in conjunction with models of perceptual decision-making, we found evidence for the slow drift in neural activity acting as an impulsivity signal, overriding sensory evidence to dictate the final decision. Overall, this work uncovers an internal state embedded in the population activity across multiple brain areas, hidden from typical trial-averaged analyses and revealed only when considering the passage of time within each experimental session. Knowledge of this cognitive factor was critical in elucidating how sensory signals and the internal state together contribute to the decision-making process.

neuroscience↗

bioRxiv2019

Barcoding and demultiplexing Oxford Nanopore native RNA sequencing reads with deep residual learning

Nanopore sequencing has enabled sequencing of native RNA molecules without conversion to cDNA, thus opening the gates to a new era for the unbiased study of RNA biology. However, a formal barcoding protocol for direct sequencing of native RNA molecules is currently lacking, limiting the efficient processing of multiple samples in the same flowcell. A major limitation for the development of barcoding protocols for direct RNA sequencing is the error rate introduced during the base-calling process, especially towards the 5 and 3 ends of reads, which complicates sequence-based barcode demultiplexing. Here, we propose a novel strategy to barcode and demultiplex direct RNA sequencing nanopore data, which does not rely on base-calling or additional library preparation steps. Specifically, custom DNA oligonucleotides are ligated to RNA transcripts during library preparation. Then, raw current signal corresponding to the DNA barcode is extracted and transformed into an array of pixels, which is used to determine the underlying barcode using a deep convolutional neural network classifier. Our method, DeePlexiCon, implements a 20-layer residual neural network model that can demultiplex 93% of the reads with 95.1% specificity, or 60% of reads with 99.9% specificity. The availability of an efficient and simple barcoding strategy for native RNA sequencing will enhance the use of direct RNA sequencing by making it more cost-effective to the entire community. Moreover, it will facilitate the applicability of direct RNA sequencing to samples where the RNA amounts are limited, such as patient-derived samples.

genomics↗

bioRxiv2019

Dynamic shifts of visual and saccadic signals in prefrontal cortical regions 8Ar and FEF

Active vision is a fundamental process by which primates gather information about the external world. Multiple brain regions have been studied in the context of simple active vision tasks in which a visual targets appearance is temporally separated from saccade execution. Most neurons have tight spatial registration between visual and saccadic signals, and in areas such as prefrontal cortex (PFC) some neurons show persistent delay activity that links visual and motor epochs and has been proposed as a basis for spatial working memory. Many PFC neurons also show rich dynamics, which have been attributed to alternative working memory codes and the representation of other task variables. Our study investigated the transition between processing a visual stimulus and generating an eye movement in populations of PFC neurons in macaque monkeys performing a memory guided saccade task. We found that neurons in two subregions of PFC, the frontal eye fields (FEF) and area 8Ar, differed in their dynamics and spatial response profiles. These dynamics could be attributed largely to shifts in the spatial profile of visual and motor responses in individual neurons. This led to visual and motor codes for particular spatial locations that were instantiated by different mixtures of neurons, which could be important in PFCs flexible role in multiple sensory, cognitive, and motor tasks.\n\nNew and NoteworthyA central question in neuroscience is how the brain transitions from sensory representations to motor outputs. The prefrontal cortex contains neurons that have long been implicated as important in this transition and in working memory. We found evidence for rich and diverse tuning in these neurons, that was often spatially misaligned between visual and saccadic responses. This feature may play an important role in flexible working memory capabilities.

neuroscience↗

bioRxiv2019

Hue tuning curves in V4 change with visual context

Neurons are often probed by presenting a set of stimuli that vary along one dimension (e.g. color) and quantifying how this stimulus property affect neural activity. An open question, in particular where higher-level areas are involved, is how much tuning measured with one stimulus set reveals about tuning to a new set. Here we ask this question by estimating tuning to hue in macaque V4 from a set of natural scenes and a set of simple color stimuli. We found that hue tuning was strong in each dataset but was not correlated across the datasets, a finding expected if neurons have strong mixed selectivity. We also show how such mixed selectivity may be useful for transmitting information about multiple dimensions of the world. Our finding suggest that tuning in higher visual areas measured with simple stimuli may thus not generalize to naturalistic stimuli. New & NoteworthyVisual cortex is often investigated by mapping neural tuning to variables selected by the researcher such as color. How much does this approach tell us a neurons general role in vision? Here we show that for strongly hue-tuned neurons in V4, estimating hue tuning from artificial stimuli does not reveal the hue tuning in the context of natural scenes. We show how models of optimal information processing suggest that such mixed selectivity maximizes information transmission.

neuroscience↗

bioRxiv2019

GPU Accelerated Adaptive Banded Event Alignment for Rapid Comparative Nanopore Signal Analysis

Nanopore sequencing has the potential to revolutionise genomics by realising portable, real-time sequencing applications, including point-of-care diagnostics and in-the-field genotyping. Achieving these applications requires efficient bioinformatic algorithms for the analysis of raw nanopore signal data. For instance, comparing raw nanopore signals to a biological reference sequence is a computationally complex task despite leveraging a dynamic programming algorithm for Adaptive Banded Event Alignment (ABEA)--a commonly used approach to polish sequencing data and identify non-standard nucleotides, such as measuring DNA methylation. Here, we parallelise and optimise an implementation of the ABEA algorithm (termed f5c) to efficiently run on heterogeneous CPU-GPU architectures. By optimising memory, compute and load balancing between CPU and GPU, we demonstrate how f5c can perform ~3-5x faster than the original implementation of ABEA in the Nanopolish software package. We also show that f5c enables DNA methylation detection on-the-fly using an embedded System on Chip (SoC) equipped with GPUs. Our work not only demonstrates that complex genomics analyses can be performed on lightweight computing systems, but also benefits High-Performance Computing (HPC). The associated source code for f5c along with GPU optimised ABEA is available at https://github.com/hasindu2008/f5c.

bioinformatics↗

bioRxiv2019

Mesocorticolimbic circuit mechanisms underlying the effects of ketamine on dopamine: a translational imaging study

Patients with schizophrenia show increased striatal dopamine synthesis capacity in imaging studies. However, the mechanism underlying this is unclear but may be due to N-methyl-D-aspartate receptor (NMDAR) hypofunction and parvalbumin (PV) neuronal dysfunction leading to disinhibition of mesostriatal dopamine neurons. Here, we test this in a translational mouse imaging study using a ketamine model. Mice were treated with sub-chronic ketamine (30mg/kg) or saline followed by in-vivo positron emission tomography of striatal dopamine synthesis capacity, analogous to measures used in patients. Locomotor activity was measured using the open field test. In-vivo cell-type-specific chemogenetic approaches and pharmacological interventions were used to manipulate neuronal excitability. Immunohistochemistry and RNA sequencing were used to investigate molecular mechanisms. Sub-chronic ketamine increased striatal dopamine synthesis capacity (Cohens d=2.5, P<0.001) and locomotor activity. These effects were countered by inhibition of midbrain dopamine neurons, and by activation of cortical and ventral subiculum PV interneurons. Sub-chronic ketamine reduced PV expression in these neurons. Pharmacological intervention with SEP-363856, a novel psychotropic agent with agonism at trace amine receptor 1 (TAAR1), significantly reduced the ketamine-induced increase in dopamine synthesis capacity. These results show that sub-chronic ketamine treatment in mice mimics the dopaminergic alterations in patients with psychosis, and suggest an underlying neurocircuit involving PV interneuron hypofunction in frontal cortex and hippocampus as well as activation of midbrain dopamine neurons. A novel TAAR1 agonist reversed the dopaminergic alterations suggesting a therapeutic mechanism for targeting presynaptic dopamine dysfunction in patients.

neuroscience↗

bioRxiv2019

A neural network for online spike classification that improves decoding accuracy

Separating neural signals from noise can improve brain-computer interface performance and stability. However, most algorithms for separating neural action potentials from noise are not suitable for use in real time and have shown mixed effects on decoding performance. With the goal of removing noise that impedes online decoding, we sought to automate the intuition of human spike-sorters to operate in real time with an easily tunable parameter governing the stringency with which spike waveforms are classified. We trained an artificial neural network with one hidden layer on neural waveforms that were hand-labeled as either spikes or noise. The network output was a likelihood metric for each waveform it classified, and we tuned the networks stringency by varying the minimum likelihood value for a waveform to be considered a spike. Using the networks labels to exclude noise waveforms, we decoded remembered target location during a memory-guided saccade task from electrode arrays implanted in prefrontal cortex of rhesus macaque monkeys. The network classified waveforms in real time, and its classifications were qualitatively similar to those of a human spike-sorter. Compared to decoding with threshold crossings, in most sessions we improved decoding performance by removing waveforms with low spike likelihood values. Furthermore, decoding with our networks classifications became more beneficial as time since array implantation increased. Our classifier serves as a feasible preprocessing step, with little risk of harm, that could be applied to both offline neural data analyses and online decoding. New & NoteworthyWhile there are many spike-sorting methods that isolate well-defined single units, these methods typically involve human intervention and have inconsistent effects on decoding. We used human classified neural waveforms as training data to create an artificial neural network that could be tuned to separate spikes from noise that impaired decoding. We found that this network operated in real time and was suitable for both offline data processing and online decoding.

neuroscience↗

bioRxiv2019

Coherent whole food web responses to outbreaking spruce budworm

The world is astoundingly variable, and individuals to whole communities must respond to variability to survive. One example of natures variability is the massive fluctuations in spruce budworm (Choristoneura fumiferana Clemens, Lepidoptera: Tortricidae) populations that occur over 35 years. We examined how the parasitoid community altered its parasitism of budworm and other caterpillar species in response to these fluctuations. Budworm and other caterpillar species were sampled from balsam fir in three plots for 14 years in Atlantic Canada, and then reared to identify any emerging parasitoids. We found that the parasitoid community showed a simple linear, indiscriminate response (i.e., no preference, where densities purely dictated parasitism rates) to changes in budworm densities relative to other caterpillar species on balsam fir. We also observed strong changes in topology and distributions of interaction strengths between the parasitoids, budworm and other caterpillar species as budworm densities fluctuated. Our study contributes to the suggestion that hardwood trees are a critical part of the budworm-parasitoid food web, where parasitoids attack other caterpillar species on hardwood trees when budworm populations are low. Taken together, our study shows that a parasitoid community collectively alters species interactions in response to variable budworm densities, fundamentally shifting food web pathways.

ecology↗

bioRxiv2019

Altered functional interactions between neurons in primary visual cortex of macaque monkeys with experimental amblyopia

Amblyopia, a disorder in which vision through one of the eyes is degraded, arises because of defective processing of information by the visual system. Amblyopia often develops in humans after early misalignment of the eyes (strabismus), and can be simulated in macaque monkeys by artificially inducing strabismus. In such amblyopic animals, single-unit responses in primary visual cortex (V1) are appreciably reduced when evoked by the amblyopic eye compared to the other (fellow) eye. However, this degradation in single V1 neuron responsivity is not commensurate with the marked losses in visual sensitivity and resolution measured behaviorally. Here we explored the idea that changes in patterns of coordinated activity across populations of V1 neurons may contribute to degraded visual representations in amblyopia, potentially making it more difficult to read out evoked activity to support perceptual decisions. We studied the visually-evoked activity of V1 neuronal populations in three macaques (M. nemestrina) with strabismic amblyopia and in one control. Activity driven through the amblyopic eye was diminished, and these responses also showed more interneuronal correlation at all stimulus contrasts than responses driven through the fellow eye or responses in the control. A decoding analysis showed that responses driven through the amblyopic eye carried less visual information than other responses. Our results suggest that part of the reduced visual capacity of amblyopes may be due to changes in the patterns of functional interaction among neurons in V1.\n\nNew and noteworthyAmblyopia is a developmental disorder of visual processing that reduces visual function and changes the visual responses of cortical neurons in macaque monkeys. The neuronal and behavioral changes are not always well correlated. We found that the interactions among neurons in the visual cortex of monkeys with amblyopia are also altered. These changes may contribute to amblyopic visual deficits by diminishing the amount of information relayed by neuronal populations driven by the amblyopic eye.

neuroscience↗