Functionally distinct GABAergic amacrine cell types regulate spatiotemporal encoding in the mouse retina

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

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Hierarchical retinal computations rely on hybrid chemical-electrical signaling

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

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Spatiotemporal properties of glutamate input support direction selectivity in the dendrites of retinal starburst amacrine cells

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

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Mammalian Retinal Bipolar Cells: Morphological Identification and Systematic Classification in Rabbit Retina With a Comparative Perspective

The Journal of Comparative Neurology, Journal Year: 2025, Volume and Issue: 533(2)

Published: Feb. 1, 2025

ABSTRACT Retinal bipolar cells (BCs) convey visual signals from photoreceptors to more than 50 types of rabbit retinal ganglion (Famiglietti, 2020). More 40 years ago, 10–11 were recognized in and cat retinas 1981). Twenty later, 10 identified mouse, rat, monkey, while recent molecular genetic studies indicate that there are 15 cell mouse retina (Shekhar et al., 2016). The present detailed study 800 11 Golgi‐impregnated indicates 14–16 cone one type rod retina. These have been carefully analyzed terms dendritic axonal morphology axon terminal stratification with respect fiducial starburst amacrine cells. In fortuitous proximity, several can be related by contacts suggestive synaptic connection. results compared other Homologies monkey considered functional terms.

Language: Английский

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Two mechanisms for direction selectivity in a model of the primate starburst amacrine cell

Visual Neuroscience, Journal Year: 2023, Volume and Issue: 40

Published: Jan. 1, 2023

Abstract In a recent study, visual signals were recorded for the first time in starburst amacrine cells of macaque retina, and, as mouse and rabbit, directional bias observed calcium was from near dendritic tips. Stimulus motion soma toward tip generated larger signal than soma. Two mechanisms affecting spatiotemporal summation excitatory postsynaptic currents have been proposed to contribute signaling at tips starbursts: (1) “morphological” mechanism which electrotonic propagation synaptic along dendrite sums bipolar cell inputs preferentially stimulus centrifugal direction; (2) “space–time” that relies on differences time-courses proximal distal favor motion. To explore contributions these two primate, we developed realistic computational model based connectomic reconstruction distribution its sustained transient types. Our suggests both can initiate direction selectivity dendrites, but their differ depending properties stimulus. Specifically, morphological dominates when small objects are moving high velocities, space–time contributes most large low velocities.

Language: Английский

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Diverse GABA signaling in the inner retina enables spatiotemporal coding

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

Published: Jan. 11, 2024

Summary paragraph GABA ( ψ -aminobutyric acid) is the primary inhibitory neurotransmitter in mammalian central nervous system (CNS) 1,2 . There a wide range of GABAergic neuronal types, each which plays an important role neural processing and etiology neurological disorders 3–5 However, there no comprehensive understanding this functional diversity, due to lack genetic tools target study multitude cell types. Here we perform two-photon imaging release inner plexiform layer (IPL) mouse retina using newly developed sensor iGABASnFR2. By applying varied light stimuli isolated retinae, reveal over 40 different GABA-releasing neurons, including some not previously described. Individual types show unique distributions synaptic sites sublayers comprising IPL, allowing layer-specific visual encoding. Synaptic input output are aligned along specific retinal orientations for multiple Furthermore, computational modeling reveals that combination type-specific spatial structure kinetics enables neurons suppress sculpt excitatory signals response behaviorally relevant motion structures. Our high-throughput approach provides first physiological characterization signaling vertebrate CNS. Future applications method will enable interrogation function dysfunction diverse circuits health disease.

Language: Английский

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Dendritic mGluR2 and perisomatic Kv3 signaling regulate dendritic computation of mouse starburst amacrine cells

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

Published: Feb. 28, 2024

Abstract Dendritic mechanisms driving input-output transformation in starburst amacrine cells (SACs) are not fully understood. Here, we combine two-photon subcellular voltage and calcium imaging electrophysiological recording to determine the computational architecture of mouse SAC dendrites. We found that perisomatic region integrates motion signals over entire dendritic field, providing a low-pass-filtered global depolarization Dendrites integrate local synaptic inputs with this signal direction-selective manner. Coincidental outward direction generate suprathreshold transients. Moreover, metabotropic glutamate receptor 2 (mGluR2) signaling SACs modulates initiation transients dendrites but at soma. In contrast, voltage-gated potassium channel 3 (Kv3) dampens fast Together, complementary mGluR2 Kv3 different regions leads compartmentalization selectivity, highlighting importance these computation.

Language: Английский

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Optical measurement of glutamate release robustly reports short-term plasticity at a fast central synapse

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Feb. 28, 2024

Introduction Recently developed fluorescent neurotransmitter indicators have enabled direct measurements of in the synaptic cleft. Precise optical release may be used to make inferences about presynaptic function independent electrophysiological measurements. Methods Here, we express iGluSnFR, a genetically encoded glutamate reporter mouse spiral ganglion neurons compare and readouts short-term plasticity at endbulb Held synapse. Results We show iGluSnFR robustly approximately linearly reports from during transmission allows assessment high-frequency train stimuli. Furthermore, that expression slightly alters time course spontaneous postsynaptic currents, but is unlikely impact evoked synchronous many vesicles. Discussion conclude monitoring with sensors fast large central synapses like feasible robust quantification some, not all aspects release.

Language: Английский

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Cone bipolar cell synapses generate transient versus sustained signals in parallel ON pathways of the mouse retina

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

Published: May 14, 2024

Abstract Parallel processing is a fundamental organizing principle in the nervous system, and understanding how parallel neural circuits generate distinct outputs from common inputs key goal of neuroscience. In mammalian retina, divergence cone signals into multiple feed-forward bipolar cell pathways forms initial basis for retinal dedicated to specific visual functions. Here, we used patch-clamp electrophysiology, electron microscopy two photon imaging fluorescent glutamate sensor examine kinetically responses arise transient versus sustained ON alpha RGCs (ON-T ON-S RGCs) mouse retina. We directly compared response properties these with their presynaptic partners, which identified using 3D reconstruction. Different subtypes (type 5i, type 6 7) had indistinguishable light-driven whereas extracellular around RGC dendrites postsynaptic excitatory currents measured ON-T identical stimuli probe cells were distinct. Anatomical examination axon terminals suggests subtype-specific differences size synaptic ribbon-associated vesicle pools may contribute kinetics. Our findings indicate synapses are primary point pathways.

Language: Английский

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Neural Circuits Underlying Multifeature Extraction in the Retina

Journal of Neuroscience, Journal Year: 2023, Volume and Issue: 44(10), P. e0910232023 - e0910232023

Published: Nov. 13, 2023

Classic ON-OFF direction-selective ganglion cells (DSGCs) that encode the four cardinal directions were recently shown to also be orientation-selective. To clarify mechanisms underlying orientation selectivity, we employed a variety of electrophysiological, optogenetic, and gene knock-out strategies test relative contributions glutamate, GABA, acetylcholine (ACh) input are known drive DSGCs, in male female mouse retinas. Extracellular spike recordings revealed DSGCs respond preferentially either vertical or horizontal bars, those perpendicular their preferred-null motion axes. By contrast, glutamate all DSGC types measured using whole-cell patch-clamp techniques was found tuned along axis. Tuned glutamatergic excitation heavily reliant on type 5A bipolar cells, which appear electrically coupled via connexin 36 containing gap junctions vertically oriented processes wide-field amacrine cells. Vertically inputs transformed by GABAergic/cholinergic "starburst" (SACs), critical components circuit, into distinct patterns inhibition excitation. Feed-forward SAC appears "veto" preferred dorsal/ventral (but not nasal/temporal) coding "flipping" tuning 90° accounts for apparent mismatch between DSGC's spiking response. Together, these results reveal how two synaptic motifs interact generate complex feature shedding light intricate circuitry underlies visual processing retina.

Language: Английский

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