Rejection of inappropriate synaptic partners mediated by transcellular FLRT2-UNC5 signaling DOI Creative Commons

Cameron L. Prigge,

Arsha Sharma,

Mayur Dembla

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Aug. 30, 2022

ABSTRACT During nervous system development, neurons choose synaptic partners with remarkable specificity; however, the cell-cell recognition mechanisms governing rejection of inappropriate remain enigmatic. Here we show that mouse retinal avoid using FLRT2-UNC5 receptor-ligand system. Within inner plexiform layer (IPL), FLRT2 is expressed by direction-selective (DS) circuit neurons, whereas UNC5C/D are non-DS projecting to adjacent IPL sublayers. In vivo gain- and loss-of-function experiments demonstrate binding eliminates growing DS dendrites have strayed from Abrogation allows mistargeted arbors persist, elaborate, acquire synapses partners. Conversely, UNC5C misexpression within sublayers inhibits dendrite growth drives into Mechanistically, UNC5s promote elimination interfering FLRT2-mediated adhesion. Based on their broad expression, FLRT-UNC5 poised exert widespread effects upon partner choices across

Language: Английский

The influence of spontaneous and visual activity on the development of direction selectivity maps in mouse retina DOI Creative Commons
Alexandre Tiriac, Karina Bistrong,

Miah N. Pitcher

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 38(2), P. 110225 - 110225

Published: Jan. 1, 2022

In mice, retinal direction selectivity is organized in a map that aligns to the body and gravitational axes of optic flow, little known about how this develops. We find maps are largely present at eye opening develop normally absence visual experience. Remarkably, mice lacking beta2 subunit neuronal nicotinic acetylcholine receptors (β2-nAChR-KO), which exhibit drastically reduced cholinergic waves first postnatal week, horizontal motion absent while vertical remains. tested several possible mechanisms could explain loss β2-nAChR-KO (wave propagation bias, FRMD7 expression, starburst amacrine cell morphology), but all were found be intact when compared with WT mice. This work establishes role for development asymmetric circuitry mediates via an unknown mechanism.

Language: Английский

Citations

37

The transcription factor Tbx5 regulates direction-selective retinal ganglion cell development and image stabilization DOI Creative Commons
Timour Al‐Khindi, Michael B. Sherman, Takashi Kodama

et al.

Current Biology, Journal Year: 2022, Volume and Issue: 32(19), P. 4286 - 4298.e5

Published: Aug. 22, 2022

Language: Английский

Citations

25

Postsynaptic neuronal activity promotes regeneration of retinal axons DOI Creative Commons
Supraja G. Varadarajan, Fei Wang, Onkar S. Dhande

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(5), P. 112476 - 112476

Published: May 1, 2023

The wiring of visual circuits requires that retinal neurons functionally connect to specific brain targets, a process involves activity-dependent signaling between axons and their postsynaptic targets. Vision loss in various ophthalmological neurological diseases is caused by damage the connections from eye brain. How targets influence ganglion cell (RGC) axon regeneration functional reconnection with remains poorly understood. Here, we established paradigm which enhancement neural activity distal optic pathway, where target reside, promotes RGC reinnervation leads rescue optomotor function. Furthermore, selective activation retinorecipient neuron subsets sufficient promote regeneration. Our findings reveal key role for neuronal repair highlight potential restore damaged sensory inputs via proper stimulation.

Language: Английский

Citations

10

Cell-type specification in the retina: Recent discoveries from transcriptomic approaches DOI Creative Commons
Yi‐Rong Peng

Current Opinion in Neurobiology, Journal Year: 2023, Volume and Issue: 81, P. 102752 - 102752

Published: July 25, 2023

Understanding the formation of complex nervous system hinges on decoding mechanism that specifies a vast array neuronal types, each endowed with unique morphology, physiology, and connectivity. As pivotal step towards addressing this problem, seminal work has been devoted to characterizing distinct types. In recent years, high-throughput, single-cell transcriptomic methods have enabled rapid inventory cell types in various regions system, retina exhibiting complete molecular characterization across many vertebrate species. This invaluable resource furnished fresh perspective for investigating principles cell-type specification, thereby advancing our understanding retinal development. Accordingly, review focuses most characterizations cells, particular focus amacrine cells ganglion cells. These investigations unearthed new insights into their specification.

Language: Английский

Citations

9

A novel artificial visual system for motion direction detection in color images DOI Creative Commons
Sichen Tao, Zhiming Zhang, Ruihan Zhao

et al.

Knowledge-Based Systems, Journal Year: 2024, Volume and Issue: 295, P. 111816 - 111816

Published: April 18, 2024

In recent years, convolutional neural networks (CNNs) have dominated the field of computer vision. Compared to traditional methods, these network algorithms exhibit strong biomimetic performance advantages in complex visual tasks due their brain-like structure. However, because some necessary characteristics are ignored, differ greatly from computational mechanisms brain. This paper starts with extracting basic features such as motion direction information brain and abstracts, generalizes models a novel artificial system (AVS) for detecting object color images based on existing relevant neurophysiological knowledge. We propose mathematical model quantification mechanism each component neuron that generates selectivity using dendritic models, spiking concepts knowledge retinal direction-selective ganglion cell pathways. The experiment is one million instances under different environments noise-free, static dynamic random noise, salt-and-pepper Gaussion light changing. comparison 4 famous CNNs, LeNet-5, EfficientNetB0, ResNet18, RegNetX-200MF, we test verify AVS's effectiveness, efficiency generalization ability well other including high biological rationality, learning-free capability, interpretability ease-of-use etc. AVS demonstrates neuroscience still has important implications guiding promoting development intelligence technology. Furthermore, firstly provides successful quantitative reference case study further understanding primary cortical encoding

Language: Английский

Citations

3

Rejection of inappropriate synaptic partners in mouse retina mediated by transcellular FLRT2-UNC5 signaling DOI Creative Commons

Cameron L. Prigge,

Mayur Dembla,

Arsha Sharma

et al.

Developmental Cell, Journal Year: 2023, Volume and Issue: 58(20), P. 2080 - 2096.e7

Published: Aug. 8, 2023

Language: Английский

Citations

7

A Novel Artificial Visual System for Motion Direction Detection in Grayscale Images DOI Creative Commons
Sichen Tao, Yuki Todo, Zheng Tang

et al.

Mathematics, Journal Year: 2022, Volume and Issue: 10(16), P. 2975 - 2975

Published: Aug. 17, 2022

How specific features of the environment are represented in mammalian brain is an important unexplained mystery neuroscience. Visual information considered to be captured most preferentially by brain. As one visual elements, motion direction receptive field thought collected already at retinal direction-selective ganglion cell (DSGC) layer. However, knowledge (DS) mechanisms retina has remained only a cellular level, and there lack complete direction-sensitivity understanding system. Previous studies DS models have been limited stage one-dimensional black-and-white (binary) images or still biological rationality. In this paper, we innovatively propose two-dimensional, eight-directional detection mechanism for grayscale called artificial system (AVS). The structure neuronal functions highly faithful neuroscientific perceptions pathway, thus biologically reasonable. particular, introducing horizontal contact pathway provided cells (HCs) inner nuclear layer forming functional collaboration with bipolar (BCs), limitation that previous can recognize object directions binary overcome; proposed model solve recognizing problem images. Through computer simulation experiments, verified AVS effective high accuracy, it not affected shape, size, location objects field. Its excellent noise immunity was also adding multiple types experimental data set. Compared classical convolutional neural network (CNN), completely significantly better terms effectiveness immunity, various advantages such as interpretability, no need learning, easy hardware implementation. addition, activation characteristics neurons consistent those real strong neurofunctional similarity brain-like superiority. Moreover, will provide novel perspective approach analyzing well principles face cognitive bottleneck on persisted nearly 60 years.

Language: Английский

Citations

11

Differential expression analysis identifies candidate synaptogenic molecules for wiring direction-selective circuits in the retina DOI
Joshua Tworig, Ryan D. Morrie, Karina Bistrong

et al.

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: unknown, P. e1461232024 - e1461232024

Published: March 21, 2024

An organizational feature of neural circuits is the specificity synaptic connections. A striking example direction-selective (DS) circuit retina. There are multiple subtypes DS retinal ganglion cells (DSGCs) that prefer motion along one four preferred directions. This computation mediated by selective wiring a single inhibitory interneuron, starburst amacrine cell (SAC), with each DSGC subtype preferentially receiving input from subset SAC processes. We hypothesize molecular basis this in part unique expression profiles subtypes. To test this, we first performed paired recordings isolated mouse retinas both sexes to determine postnatal day 10 (P10) represents age at which asymmetric synapses form. Second, RNA sequencing and differential analysis on P10 ON-OFF DSGCs tuned for either nasal or ventral identified candidates may promote direction-specific wiring. then used conditional knock-out strategy role candidate, secreted organizer cerebellin-4 (Cbln4), development tuning. Using two-photon calcium imaging, observed small deficit directional tuning among ventral-preferring lacking Cbln4, though whole-cell voltage-clamp did not identify significant change inputs. suggests Cbln4 does function primarily via cell-autonomous mechanism instruct circuits. Nevertheless, our transcriptomic candidate factors gaining insights into mechanisms circuit.

Language: Английский

Citations

2

Cellular and Molecular Mechanisms Regulating Retinal Synapse Development DOI
Whitney A. Stevens-Sostre, Mrinalini Hoon

Annual Review of Vision Science, Journal Year: 2024, Volume and Issue: 10(1), P. 377 - 402

Published: Sept. 15, 2024

Synapse formation within the retinal circuit ensures that distinct neuronal types can communicate efficiently to process visual signals. Synapses thus form core of computations performed by circuit. Retinal synapses are diverse but be broadly categorized into multipartner ribbon and 1:1 conventional synapses. In this article, we review our current understanding cellular molecular mechanisms regulate functional establishment mammalian synapses, including role adhesion proteins, synaptic extracellular matrix cytoskeletal-associated activity-dependent cues. We outline future directions areas research will expand knowledge these mechanisms. Understanding regulators moderating synapse function not only reveals integrated developmental processes establish circuits, also divulges identity could engaged during disease degeneration.

Language: Английский

Citations

2

Molecular and spatial analysis of ganglion cells on retinal flatmounts: diversity, topography, and perivascularity DOI Creative Commons
Nicole Tsai,

Kushal Nimkar,

Mengya Zhao

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 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.

Language: Английский

Citations

2