Genetically defined neuron types underlying visuomotor transformation in the superior colliculus

Nature reviews. Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 27, 2024

Language: Английский

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Coordination of distinct sources of excitatory inputs enhances motion selectivity in the mouse visual thalamus

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Multiple sources innervate the visual thalamus to influence image-forming vision prior cortex, yet it remains unclear how non-retinal and retinal input coordinate shape thalamic selectivity. Using dual-color two-photon calcium imaging in of awake mice, we observed similar coarse-scale retinotopic organization between axons superior colliculus neurons ganglion cells, both providing strong converging excitatory neurons. At a fine scale ∼10 µm, collicular boutons often shared feature preferences with nearby boutons. Inhibiting significantly suppressed responses specifically reduced motion selectivity preferring nasal-to-temporal motion. The reduction could be result silencing sharply tuned direction-selective colliculogeniculate input. These findings suggest that is not merely relay but selectively integrates inputs from multiple regions build stimulus information transmitted cortex. Chronic reveals diverse tuning axonal boutons.Nearby share at µm scaleSilencing suppresses majority neurons.Silencing reduces

Language: Английский

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Optic nerve injury impairs intrinsic mechanisms underlying electrical activity in a resilient retinal ganglion cell

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 22, 2025

Abstract Retinal ganglion cells (RGCs) are the sole output neurons of retina and convey visual information to brain via their axons in optic nerve. Following injury nerve, RGC degenerate many die. For example, a model axon injury, nerve crush (ONC), kills ∼80% RGCs after 2 weeks. Surviving biased towards ‘resilient’ types, including several with sustained firing light stimulation. survival may depend on activity, there is limited understanding how or why activity changes following injury. Here we quantified electrophysiological properties highly resilient type, ON‐Alpha (AlphaONS) RGC, 7 days ONC extracellular whole‐cell patch clamp recording. Both light‐ current‐driven were reduced ONC, but synaptic inputs largely intact. Resting membrane potential input resistance relatively unchanged, while voltage‐gated currents impaired, reduction sodium channel current density initial segment. Hyperpolarization chelation intracellular calcium partially rescued rates. Extracellular recordings at 3 showed normal light‐evoked from AlphaONS other Alpha RGCs, susceptible types. These data suggest that an injured reduces its by 1 week as consequence downregulation intrinsic excitability Ca 2+ ‐dependent mechanism. Reduced be due degradation could also energetically beneficial, preserving energy for regeneration. image Key points cell (RGC) types show diverse rates A type (sustained RGC) maintains The shows diminished expression segment genes Activity deficits reflect dysfunction (Na + channels, ), not input. intact suggesting this time point does predict resilience.

Language: Английский

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A light-responsive neural circuit suppresses feeding

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 44(30), P. e2192232024 - e2192232024

Published: June 19, 2024

Light plays an essential role in a variety of physiological processes, including vision, mood, and glucose homeostasis. However, the intricate relationship between light animal's feeding behavior has remained elusive. Here, we found that exposure suppresses food intake, whereas darkness amplifies it male mice. Interestingly, this phenomenon extends its reach to diurnal Nile grass rats healthy humans. We further show lateral habenula (LHb) neurons mice respond exposure, which turn activates 5-HT dorsal Raphe nucleus (DRN). Activation LHb→5-HT

Language: Английский

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

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

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Optic nerve injury impairs intrinsic mechanisms underlying electrical activity in a resilient retinal ganglion cell

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

Published: Feb. 23, 2024

Abstract Retinal ganglion cells (RGCs) are the sole output neurons of retina and convey visual information to brain via their axons in optic nerve. Following an injury nerve, RGCs degenerate many die. For example, a surgical model compressive axon injury, nerve crush (ONC), kills ∼80% after two weeks. Surviving biased towards certain ‘resilient’ types, including several types that originally produced sustained firing light stimulation. RGC survival may depend on activity level, there is limited understanding how or why changes following injury. Here we quantified electrophysiological properties highly resilient type, ON-Alpha RGC, seven days post-ONC with extracellular whole-cell patch clamp recording. Both light- current-driven were reduced ONC, but synaptic inputs largely intact. Resting membrane potential input resistance relatively unchanged, while voltage-gated currents impaired, reduction sodium channel density initial segment function. Hyperpolarization chelation intracellular calcium partially rescued rates. These data suggest injured reduces its by combination expression function downregulation intrinsic excitability Ca 2+ -dependent mechanism without substantial input. Reduced be due degradation could also energetically beneficial for RGCs, preserving cellular energy regeneration. Graphical Schematic view effects (optic crush) physiology (AlphaONS) retinal cell. survive weeks other cell perish. At one week AlphaONS has diminished spontaneous light-evoked action firing. depends not rather reductions excitability. explained Key Points Summary 1) (RGC) show diverse rates 2) A type maintains post-injury. 3) The shows (AIS) genes 4) Activity deficits arise from dysfunction (Na + channels, ), loss excitation enhanced inhibition.

Language: Английский

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Specific retinal neurons regulate context-dependent defensive responses to visual threat

PNAS Nexus, Journal Year: 2024, Volume and Issue: 3(10)

Published: Sept. 24, 2024

Abstract While encountering a visual threat, an animal assesses multiple factors to choose appropriate defensive strategy. For example, when rodent detects looming aerial predator, its behavioral response can be influenced by specific environmental context, such as the availability of shelter. Indeed, rodents typically escape from stimulus shelter is present; otherwise, they freeze. Here we report that context-dependent responses initiated at earliest stage system distinct types retinal ganglion cells (RGCs), retina's output neurons. Using genetically defined cell ablation in mature mice, discovered some RGC were necessary for either escaping (alpha RGCs) or freezing (intrinsically photosensitive but not both behaviors; whereas other required behavior (direction-selective RGCs preferring vertical motion). Altogether, our results suggest regulate elicited same threatening depending on contextual signals environment. These findings emphasize unique contribution early pathways evolutionally conserved reactions.

Language: Английский

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Transcriptomic changes in retinal ganglion cell types associated with the disruption of cholinergic retinal waves

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

Published: Dec. 9, 2024

Abstract In the early stages of retinal development, a form correlated activity known as waves causes periodic depolarizations immature ganglion cells (RGCs). Retinal are crucial for refining visual maps in brain’s retinofugal targets and development circuits underlying feature detection, such direction selectivity. Yet, how alter gene expression RGCs is poorly understood, particularly at level many distinct types that underlie retina’s ability to encode diverse features. We performed single-cell RNA sequencing on isolated end first postnatal week from wild-type (WT) mice β2KO mice, which lack β2 subunit nicotinic acetylcholine receptor, leading disruption cholinergic waves. Statistical comparisons RGC transcriptomes between two conditions reveal weak impact diversity, indicating do not influence molecular programs instruct differentiation maturation. Although wave-dependent changes modest global sense, we identified ∼238 genes significantly altered select subsets types. focused one gene, Kcnk9 , encodes two-pore domain leak channel potassium TASK3. highly enriched αRGCs, was strongly downregulated β2KO. validated this result using situ hybridization whole-cell recording demonstrate significant decrease conductance RGCs. Our dataset provides useful resource identifying potential spontaneous activity-dependent regulation neurodevelopment retina.

Language: Английский

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