New insights into retinal circuits through EM connectomics: what we have learnt and what remains to be learned DOI Creative Commons

Abhilash Sawant,

Aindrila Saha,

Jacob Khoussine

et al.

Frontiers in Ophthalmology, Journal Year: 2023, Volume and Issue: 3

Published: April 20, 2023

The retinal neural circuit is intricately wired for efficient processing of visual signals. This well-supported by the specialized connections between neurons at both functional and ultrastructural levels. Through 3D electron microscopic (EM) reconstructions circuits we have learnt much about specificities within layers including new insights into how establish perform sophisticated computations. mini-review will summarize circuitry provide details novel EM connectomics has brought our understanding circuitry. We also discuss unresolved questions that can be addressed in future.

Language: Английский

Origins of direction selectivity in the primate retina DOI Creative Commons
Yeon Jin Kim,

Beth B. Peterson,

Joanna D. Crook

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: May 23, 2022

From mouse to primate, there is a striking discontinuity in our current understanding of the neural coding motion direction. In non-primate mammals, directionally selective cell types and circuits are signature feature retina, situated at earliest stage visual process. primates, by contrast, direction selectivity hallmark processing areas cortex, but has not been found despite significant effort. Here we combined functional recordings light-evoked responses connectomic reconstruction identify diverse direction-selective macaque monkey retina with distinctive physiological properties synaptic motifs. This circuitry includes an ON-OFF ganglion type, spiking, polyaxonal amacrine starburst cell, all which show selectivity. Moreover, discovered that cells possess strong, non-GABAergic, antagonistic surround mediated input from excitatory bipolar critical for generation radial sensitivity these cells. Our findings open door investigation precortical computes primate system.

Language: Английский

Citations

51

Functionally distinct GABAergic amacrine cell types regulate spatiotemporal encoding in the mouse retina DOI Creative Commons
Akihiro Matsumoto,

Jacqueline Morris,

Loren L. Looger

et al.

Nature Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

GABA (γ-aminobutyric acid) is the primary inhibitory neurotransmitter in mammalian central nervous system. GABAergic neuronal types play important roles neural processing and etiology of neurological disorders; however, there no comprehensive understanding their functional diversity. Here we perform two-photon imaging release inner plexiform layer male female mice retinae (8-16 weeks old) using sensor iGABASnFR2. By applying varied light stimuli to isolated retinae, reveal over 40 different GABA-releasing neuron types. Individual show layer-specific visual encoding within sublayers. Synaptic input output sites are aligned along specific retinal orientations. The combination cell type-specific spatial structure unique kinetics enables neurons sculpt excitatory signals response a wide range behaviorally relevant motion structures. Our findings emphasize importance diversity intricate specialization

Language: Английский

Citations

1

Center-surround interactions underlie bipolar cell motion sensitivity in the mouse retina DOI Creative Commons
Sarah Strauß,

Maria M. Korympidou,

Yanli Ran

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Sept. 26, 2022

Motion sensing is a critical aspect of vision. We studied the representation motion in mouse retinal bipolar cells and found that some are radially direction selective, preferring origin small object trajectories. Using glutamate sensor, we directly observed synaptic output there radial selective non-selective cell types, majority being selectivity relies on properties center-surround receptive field. used these fields along with connectomics to design biophysical models downstream cells. The additional experiments demonstrated pass excitation starburst amacrine cells, which contributes their directional tuning. As provide most ganglion may contribute processing throughout visual system.

Language: Английский

Citations

33

Hierarchical retinal computations rely on hybrid chemical-electrical signaling DOI Creative Commons
Laura Hanson,

Prathyusha Ravi-Chander,

David M. Berson

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(2), P. 112030 - 112030

Published: Jan. 25, 2023

Bipolar cells (BCs) are integral to the retinal circuits that extract diverse features from visual environment. They bridge photoreceptors ganglion cells, source of output. Understanding how such encode requires an accounting mechanisms control glutamate release bipolar cell axons. Here, we demonstrate orientation selectivity in a specific genetically identifiable type mouse cell-type 5A (BC5A). Their synaptic terminals respond best when stimulated with vertical bars far larger than their dendritic fields. We provide evidence this involves enhanced excitation for stimuli gap junctional coupling through connexin36. also show is detectable postsynaptically direction-selective which were not previously thought be selective orientation. Together, these results multiple extracted by single hierarchical network, engaging distinct electrical and chemical pathways.

Language: Английский

Citations

23

A presynaptic source drives differing levels of surround suppression in two mouse retinal ganglion cell types DOI Creative Commons
David Swygart, Wan‐Qing Yu, Shunsuke Takeuchi

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 18, 2024

Abstract In early sensory systems, cell-type diversity generally increases from the periphery into brain, resulting in a greater heterogeneity of responses to same stimuli. Surround suppression is canonical visual computation that begins within retina and found at varying levels across retinal ganglion cell types. Our results show level surround occurs subcellularly bipolar synapses. Using single-cell electrophysiology serial block-face scanning electron microscopy, we two types exhibit very different even though they receive input This divergence signal through synapse-specific regulation by amacrine cells scale tens microns. These findings indicate each synapse single can carry unique signal, expanding number possible functional channels earliest stages processing.

Language: Английский

Citations

8

Classical center-surround receptive fields facilitate novel object detection in retinal bipolar cells DOI Creative Commons

John A. Gaynes,

Samuel A. Budoff,

Michael J. Grybko

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Sept. 26, 2022

Antagonistic interactions between center and surround receptive field (RF) components lie at the heart of computations performed in visual system. Circularly symmetric center-surround RFs are thought to enhance responses spatial contrasts (i.e., edges), but how edges affect motion processing is unclear. Here, we addressed this question retinal bipolar cells, first neuron with classic interactions. We found that glutamate release emphasizes objects emerge RF; their continuous smaller, slower, cannot be predicted by signals elicited stationary stimuli. In our hands, alteration signal dynamics induced novel was more pronounced than edge enhancement could explained priming RF during motion. These findings echo salience human perception demonstrate an unappreciated capacity architecture facilitate object detection dynamic representation.

Language: Английский

Citations

25

Spatiotemporal properties of glutamate input support direction selectivity in the dendrites of retinal starburst amacrine cells DOI Creative Commons
Prerna Srivastava,

Geoff de Rosenroll,

Akihiro Matsumoto

et al.

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Nov. 8, 2022

The asymmetric summation of kinetically distinct glutamate inputs across the dendrites retinal ‘starburst’ amacrine cells is one several mechanisms that have been proposed to underlie their direction-selective properties, but experimentally verifying input kinetics has a challenge. Here, we used two-photon sensor (iGluSnFR) imaging directly measure individual starburst dendrites. We found signals measured from proximal were relatively sustained compared those distal These differences observed range stimulus sizes and appeared be shaped mainly by excitatory rather than inhibitory network interactions. Temporal deconvolution analysis suggests steady-state vesicle release rate was ~3 times larger at sites sites. Using connectomics-inspired computational model, demonstrate play an important role in shaping direction selectivity low velocities. Taken together, these results provide direct support for ‘space-time wiring’ model selectivity.

Language: Английский

Citations

25

Distributed feature representations of natural stimuli across parallel retinal pathways DOI Creative Commons
Jen-Chun Hsiang, Ning Shen, Florentina Soto

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 1, 2024

Abstract How sensory systems extract salient features from natural environments and organize them across neural pathways is unclear. Combining single-cell population two-photon calcium imaging in mice, we discover that retinal ON bipolar cells (second-order neurons of the visual system) are divided into two blocks four types. The distribute temporal spatial information encoding, respectively. cell axons co-stratify within each block, but separate laminarly between (upper block: diverse temporal, uniform tuning; lower spatial, tuning). similarly artificial naturalistic stimuli. In addition, they differ sensitivity to coherent motion movies. Motion distributed upper blocks, multiplexed with contrast, independent scenes. Comparing responses different boutons same arbor, find all types function as computational units. Thus, our results provide insights feature extraction stimuli reveal how structural functional organization cooperate generate parallel for mammalian retina.

Language: Английский

Citations

4

Incomplete remyelination via therapeutically enhanced oligodendrogenesis is sufficient to recover visual cortical function DOI Creative Commons
Gustavo Della‐Flora Nunes, Lindsay A. Osso,

Johana A. Haynes

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 16, 2025

Myelin loss induces neural dysfunction and contributes to the pathophysiology of neurodegenerative diseases, injury conditions, aging. Because remyelination is often incomplete, better understanding endogenous developing therapies that restore function are clinical imperatives. Here, we use in vivo two-photon microscopy electrophysiology study dynamics therapeutic-induced cortical functional recovery after cuprizone-mediated demyelination mice. We focus on visual pathway, which uniquely positioned provide insights into structure-function relationships during de/remyelination. show driven by recent oligodendrocyte highly efficacious following mild demyelination, but fails population when high rates occur quickly. Testing a thyromimetic (LL-341070) compared clemastine, find it enhances gain hastens neuronal function. The therapeutic benefit temporally restricted, acts exclusively moderate severe eliminating deficit. However, regeneration oligodendrocytes myelin healthy levels not necessary for These findings advance our its impact inform future strategies.

Language: Английский

Citations

0

A spherical code of retinal orientation selectivity enables decoding in ensembled and retinotopic operation DOI Creative Commons
Dimitrios Daniel Laniado, Yariv Maron,

John A. Gemmer

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(3), P. 115373 - 115373

Published: March 1, 2025

Language: Английский

Citations

0