Molecular and spatial analysis of ganglion cells on retinal flatmounts: diversity, topography, and perivascularity

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 17, 2024

Diverse retinal ganglion cells (RGCs) transmit distinct visual features from the eye to brain. Recent studies have categorized RGCs into 45 types in mice based on transcriptomic profiles, showing strong alignment with morphological and electrophysiological properties. However, little is known about how these are spatially arranged two-dimensional surface-an organization that influences encoding-and their local microenvironments impact development neurodegenerative responses. To address this gap, we optimized a workflow combining imaging-based spatial transcriptomics (MERFISH) immunohistochemical co-staining thin flatmount sections. We used computational methods register en face somata distributions of all molecularly defined RGC types. More than 75% (34/45) exhibited non-uniform distributions, likely reflecting adaptations retina's anatomy animal's environment. By analyzing neighborhoods each cell, identified perivascular located near blood vessels. Seven enriched niche, including members intrinsically photosensitive (ipRGC) direction-selective (DSGC) subclasses. Orthologous human counterparts - Melanopsin-enriched ipRGCs ON DSGCs were also proximal vessels, suggesting perivascularity may be evolutionarily conserved. Following optic nerve crush mice, M1-ipRGCs showed preferential survival, proximity vessels render cell-extrinsic neuroprotection through an mTOR-independent mechanism. Overall, our work offers resource characterizing profiles types, enabling future development, physiology, neurodegeneration at individual neuron type resolution across space.

Язык: Английский

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Roles of visually evoked and spontaneous activity in the development of retinal direction selectivity maps

Trends in Neurosciences, Год журнала: 2022, Номер 45(7), С. 529 - 538

Опубликована: Апрель 29, 2022

Язык: Английский

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Retina-derived signals control pace of neurogenesis in visual brain areas but not circuit assembly

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Сен. 27, 2023

Brain development is orchestrated by both innate and experience-dependent mechanisms, but their relative contributions are difficult to disentangle. Here we asked if how central visual areas altered in a vertebrate brain depleted of any all signals from retinal ganglion cells throughout development. We transcriptionally profiled neurons pretectum, thalamus other retinorecipient larval zebrafish searched for changes lakritz mutants that lack connections. Although individual genes dysregulated, the complete set 77 neuronal types develops apparently normal proportions, at locations, along differentiation trajectories. Strikingly, cell-cycle exits proliferating progenitors these delayed, greater fraction early postmitotic precursors remain uncommitted or diverted pre-glial fate. Optogenetic stimulation targeting groups normally involved processing information evokes behaviors indistinguishable wildtype. In conclusion, show emitted axons influence pace neurogenesis areas, do not detectably affect specification wiring downstream neurons.

Язык: Английский

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Retinal ganglion cell-derived semaphorin 6A segregates starburst amacrine cell dendritic scaffolds to organize the inner retina

Development, Год журнала: 2024, Номер 151(22)

Опубликована: Ноя. 4, 2024

ABSTRACT To form functional circuits, neurons must settle in their appropriate cellular locations, and then project elaborate neurites to contact target synaptic neuropils. Laminar organization within the vertebrate retinal inner plexiform layer (IPL) facilitates pre- postsynaptic neurite targeting, yet precise mechanisms underlying establishment of IPL subdomains are not well understood. Here, we explore defining compartmentalization OFF ON generally, direction-selective specifically, developing mouse IPL. We show that semaphorin 6A (Sema6A), a repulsive axon guidance cue, is required for delineation versus circuits IPL: Sema6a null IPL, boundary between domains blurred. Furthermore, Sema6A expressed by ganglion cells (RGCs) directs laminar segregation starburst amacrine cell dendritic scaffolds, which themselves serve as substrate upon other elaborate. These results demonstrate RGCs, first type neuron born retina, play an active role specialization

Язык: Английский

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Retinal input influences pace of neurogenesis but not cell-type configuration of the visual forebrain

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2021, Номер unknown

Опубликована: Ноя. 16, 2021

Summary The brain is assembled during development by both innate and experience-dependent mechanisms 1–7 , but the relative contribution of these factors poorly understood. Axons retinal ganglion cells (RGCs) connect eye to brain, forming a bottleneck for transmission visual information central areas. RGCs secrete molecules from their axons that control proliferation, differentiation migration downstream components 7–9 . Spontaneously generated waves activity, also intense stimulation, can entrain responses 10 neurons 11–16 Here we asked how cellular composition targets altered in vertebrate depleted input throughout development. For this, first established molecular catalog 17 gene expression atlas 18 neuronal subpopulations retinorecipient areas larval zebrafish. We then searched changes lakritz ( atoh7 - ) mutants, which do not form 19 Although individual forebrain-expressed genes are dysregulated complete set 77 putative cell types thalamus, pretectum tectum present. While neurogenesis trajectories overall unaltered, greater proportion remain an uncommitted progenitor stage mutant. Optogenetic stimulation pretectal area 20,21 evokes behavior blind mutants indistinguishable wildtype. Our analysis shows that, this system, produced more slowly, specified wired up proper configuration absence any signals.

Язык: Английский

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PyOKR: A Semi-Automated Method for Quantifying Optokinetic Reflex Tracking Ability

Journal of Visualized Experiments, Год журнала: 2024, Номер 206

Опубликована: Апрель 12, 2024

The study of behavioral responses to visual stimuli is a key component understanding system function. One notable response the optokinetic reflex (OKR), highly conserved innate behavior necessary for image stabilization on retina. OKR provides robust readout tracking ability and has been extensively studied understand circuitry function in animals from different genetic backgrounds. consists two phases: slow phase as eye follows stimulus edge plane compensatory fast saccade that resets position orbit. Previous methods gain quantification, although reliable, are labor intensive can be subjective or arbitrarily derived. To obtain more rapid reproducible quantification ability, we have developed novel semi-automated analysis program, PyOKR, allows two-dimensional motion any directional stimulus, addition being adaptable type video-oculography equipment. This method automated filtering, selection phases, modeling vertical horizontal vectors, movement gains relative speed, organization resultant data into usable spreadsheet statistical graphical comparisons. quantitative streamlined pipeline, readily accessible via PyPI import, direct measurement responses, thereby facilitating responses.

Язык: Английский

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Emergence of input selective recurrent dynamics via information transfer maximization

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Июнь 13, 2024

Abstract Network structures of the brain have wiring patterns specialized for specific functions. These are partially determined genetically or evolutionarily based on type task stimulus. important in information processing; however, their organizational principles not fully understood. This study frames maximization transmission alongside reduction maintenance costs as a multi-objective optimization challenge, utilizing theory and evolutionary computing algorithms with an emphasis visual system. The goal is to understand underlying circuit formation by exploring processing. demonstrates that efficient necessitates sparse circuits internal modular featuring distinct patterns. Significant trade-offs underscore necessity balance pattern development. dynamics effective exhibit moderate flexibility response stimuli, line observations from prior system studies. Maximizing transfer may allow self-organization processing functions similar actual biological circuits, without being limited modality. offers insights into neuroscience potential improve reservoir performance.

Язык: Английский

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Artificial Visual Network with Fully Modeled Retinal Direction-Selective Neural Pathway for Motion Direction Detection in Grayscale Scenes

Symmetry, Год журнала: 2024, Номер 16(12), С. 1592 - 1592

Опубликована: Ноя. 28, 2024

The complexity and functional evolution of mammalian visual systems have always been a focal point in neuroscience biological science research. primary neurons that output motion direction signals research for nearly 130 years. These are widely present the cortex retina mammals. Although relevant pathways discovered studied almost 60 years due to experimental accessibility, still remains at cellular level. specific functions overall operational mechanisms component direction-selective yet be clearly elucidated. In this study, we modeled existing conclusions based on symmetry asymmetry whole cells retina-to-cortex pathway proposed quantitative mechanism selectivity pathways, called Artificial Visual System (AVS). By tests 1 million instances 2D, eight-direction grayscale moving objects, including 10 randomly shaped objects various sizes, confirm AVS’s high effectiveness detecting. Furthermore, by comparing AVS with two well-known convolutional neural networks, namely LeNet-5 EfficientNetB0, verify its efficiency, generalization, noise resistance. Moreover, analysis indicates exhibits evident biomimetic characteristics application advantages concerning hardware implementation, plausibility, interpretability, parameter count, learning difficulty.

Язык: Английский

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Characterization of non-alpha retinal ganglion cell injury responses reveals a possible block to restoring ipRGC function

Experimental Neurology, Год журнала: 2022, Номер 357, С. 114176 - 114176

Опубликована: Июль 20, 2022

Язык: Английский

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A semi-automated method for quantifying optokinetic reflex tracking acuity

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Авг. 6, 2023

ABSTRACT The study of murine behavioral responses to visual stimuli is a key component understanding mammalian circuitry. One notable response the optokinetic reflex (OKR), highly conserved innate behavior necessary for image stabilization on retina. OKR provides robust readout tracking ability and has been extensively studied understand logic system circuitry function in mice from different genetic backgrounds. consists two phases: slow phase as eye follows stimulus edge plane, compensatory fast saccade that maintains within field. Assessment previously relied counting individual saccades estimate speed. To obtain more direct quantification ability, we have developed novel, semi-automated analysis program allows rapid reproducible unidirectional gains, addition being adaptable any video-oculography equipment. Our selection phases, modeling vertical horizontal vectors, movement relative stimulus, organization resultant data into usable spreadsheet statistical graphical comparisons. This quantitative streamlined pipeline faster measurement responses, thereby facilitating further responses. SUMMARY We describe here method directly measures resulting two-dimensional motion. A Python-based user interface algorithm higher throughput measurements parameters than previous methods.

Язык: Английский

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