Unified classification of mouse retinal ganglion cells using function, morphology, and gene expression

Cell Reports, Год журнала: 2022, Номер 40(2), С. 111040 - 111040

Опубликована: Июль 1, 2022

Classification and characterization of neuronal types are critical for understanding their function dysfunction. Neuronal classification schemes typically rely on measurements electrophysiological, morphological, molecular features, but aligning such datasets has been challenging. Here, we present a unified mouse retinal ganglion cells (RGCs), the sole output neurons. We use visually evoked responses to classify 1,859 RGCs into 42 types. also obtain morphological or transcriptomic data from subsets these align functional publicly available datasets. create an online database that allows users browse download light using machine learning algorithm. This work provides resource studies RGCs, upstream circuits in retina, projections brain, establishes framework future efforts open distribution.

Язык: Английский

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Encoding of environmental illumination by primate melanopsin neurons

Science, Год журнала: 2023, Номер 379(6630), С. 376 - 381

Опубликована: Янв. 26, 2023

Light regulates physiology, mood, and behavior through signals sent to the brain by intrinsically photosensitive retinal ganglion cells (ipRGCs). How primate ipRGCs sense light is unclear, as they are rare challenging target for electrophysiological recording. We developed a method of acute identification within live, ex vivo retina. Using it, we found that macaque monkey highly specialized encode irradiance (the overall intensity illumination) blurring spatial, temporal, chromatic features visual scene. describe mechanisms at molecular, cellular, population scales support encoding across orders-of-magnitude changes in intensity. These conserved quantitatively ~70 million years evolution separate macaques from mice.

Язык: Английский

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A presynaptic source drives differing levels of surround suppression in two mouse retinal ganglion cell types

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 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.

Язык: Английский

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Spike desensitisation as a mechanism for high-contrast selectivity in retinal ganglion cells

Frontiers in Cellular Neuroscience, Год журнала: 2024, Номер 17

Опубликована: Янв. 10, 2024

In the vertebrate retina, several dozens of parallel channels relay information about visual world to brain. These are represented by different types retinal ganglion cells (RGCs), whose responses rendered selective for distinct sets features various mechanisms. mechanisms can be roughly grouped into synaptic interactions and cell-intrinsic mechanisms, with latter including dendritic morphology as well ion channel complement distribution. Here, we investigate how strongly shape RGC output comparing two mouse types, well-described ON alpha cell a little-studied that is EGFP-labelled in

Язык: Английский

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Engram mechanisms of memory linking and identity

Nature reviews. Neuroscience, Год журнала: 2024, Номер 25(6), С. 375 - 392

Опубликована: Апрель 25, 2024

Язык: Английский

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Retinal ganglion cells adapt to ionic stress in experimental glaucoma

Frontiers in Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Март 27, 2023

Identification of early adaptive and maladaptive neuronal stress responses is an important step in developing targeted neuroprotective therapies for degenerative disease. In glaucoma, retinal ganglion cells (RGCs) their axons undergo progressive degeneration resulting from driven by sensitivity to intraocular pressure (IOP). Despite that can effectively manage IOP many patients progress vision loss, necessitating development neuronal-based therapies. Evidence experimental models glaucoma indicates the disease RGCs experience altered excitability are challenged with dysregulated potassium (K+) homeostasis. Previously we demonstrated certain RGC types have distinct profiles thresholds depolarization block, which associated extracellular K+. Here, used our inducible mouse model investigate how K+ changes exposure elevated IOP. controls, conditions increased enhanced membrane depolarization, reduced action potential generation, widened potentials. Consistent previous work, 4 weeks elevation diminished light-and current-evoked responses. Compared found effects on block threshold, IOP-exposed maintaining greater excitability. Finally, did not alter axon initial segment dimensions, suggesting structural plasticity alone cannot explain decreased sensitivity. Thus, response prolonged process reduces while diminishing These experiments give insight into lay groundwork mechanistic investigation targets therapy.

Язык: Английский

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Nitric oxide modulates contrast suppression in a subset of mouse retinal ganglion cells

eLife, Год журнала: 2025, Номер 13

Опубликована: Янв. 9, 2025

Neuromodulators have major influences on the regulation of neural circuit activity across nervous system. Nitric oxide (NO) has been shown to be a prominent neuromodulator in many circuits and extensively studied retina. Here, it associated with light adaptation, gain control, gap junctional coupling, but its effect retinal output, specifically different types ganglion cells (RGCs), is still poorly understood. In this study, we used two-photon Ca 2+ imaging multi-electrode array (MEA) recordings measure light-evoked RGCs cell layer ex vivo mouse This approach allowed us investigate neuromodulatory effects NO type-level. Our findings reveal that selectively modulates suppression temporal responses distinct subset contrast-suppressed RGC types, increasing their without altering spatial properties receptive fields. Given under photopic conditions, release triggered by quick changes levels, propose these signal fast contrast higher visual regions. Remarkably, found about one-third recorded using imaging, exhibited consistent, type-specific adaptational response throughout an experiment, independent NO. By employing sequential-recording paradigm, could disentangle those additional from drug-induced modulations. Taken together, our research highlights selective emphasizes need considering non-pharmacological changes, like such study designs.

Язык: Английский

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

The Journal of Physiology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 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.

Язык: Английский

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Homeostatic plasticity in the retina

Progress in Retinal and Eye Research, Год журнала: 2022, Номер 94, С. 101131 - 101131

Опубликована: Окт. 13, 2022

Язык: Английский

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Differences in nonlinearities determine retinal cell types

Journal of Neurophysiology, Год журнала: 2023, Номер 130(3), С. 706 - 718

Опубликована: Авг. 16, 2023

Classifying neurons in different types is still an open challenge. In the retina, recent works have taken advantage of ability to record from a large number cells classify ganglion into based on functional information. Although first attempts this direction used receptive field properties each cell them, more approaches proposed cluster directly their response stimuli. These two not been compared directly. Here, we recorded responses and methods for classifying them groups, one properties, other using stimuli with various temporal frequencies. We show that response-based approach allows separation than field-based method, leading better classification. This granularity due fact method takes account only linear part function but also some nonlinearities. A careful characterization nonlinear processing thus key allowing classification sensory neurons.NEW & NOTEWORTHY can be classified visual are modeling fields, others rely characteristic these classes latter provides higher discrimination performance. gain arises behavior neurons.

Язык: Английский

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