Biology subjects

Feller, M. B.

Publications and source records attributed to Feller, M. B..

6 recordsLinked to original sources

bioRxiv2026

Retinal waves shape starburst amacrine cell dendrite development through a direction-selective dendritic computation

During development, dendrites undergo structural plasticity in response to neural activity; however, whether spatiotemporal activity patterns can instruct dendritic growth remains unclear. Prior to vision, the developing mouse retina exhibits spontaneous retinal waves with a nasal propagation bias that mimics forward optic flow. Here, we reveal that starburst amacrine cells use direction-selective dendritic computations to transform this propagation bias into asymmetric dendrite growth, linking activity patterns to structural development.

neuroscience↗

bioRxiv2024

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

In the early stages of development, correlated activity known as retinal waves causes periodic depolarizations of retinal ganglion cells (RGCs). The {beta}2KO mouse, which lacks the {beta}2 subunit of the nicotinic acetylcholine receptor, serves as a model for understanding the role of these cholinergic waves. {beta}2KO mice have disruptions in several developmental processes of the visual system, including reduced retinotopic and eye-specific refinement of RGC axonal projections to their primary brain targets and an impact on the retinal circuits underlying direction selectivity. However, the effects of this mutation on gene expression in individual functional RGC types remain unclear. Here, we performed single-cell RNA sequencing on RGCs isolated at the end of the first postnatal week from wild-type and {beta}2KO mice. We found that in {beta}2KO mice, the molecular programs governing RGC differentiation were not impacted and the magnitude of transcriptional changes was modest compared to those observed during two days of normal postnatal maturation. This contrasts with the substantial transcriptomic changes seen in downstream visual system areas under wave disruption in recent studies. However, we identified [~]238 genes whose expression was altered in a type-specific manner. We confirmed this result via in situ hybridization and whole-cell recording by focusing on one of the downregulated genes in aRGCs, Kcnk9, which encodes the two-pore domain leak potassium channel TASK3. Our study reveals a limited transcriptomic impact of cholinergic signaling in the retina and instead of affecting all RGCs uniformly, these waves show subtle modulation of molecular programs in a type-specific manner. SIGNIFICANCE STATEMENTSpontaneous retinal waves are critical for the development of the mammalian visual system. However, their role in transcriptional regulation in the retina across the diverse retinal ganglion cell (RGC) types that underpin the detection and transmission of visual features is unclear. Using single-cell RNA sequencing, we analyzed RGC transcriptome from wild-type mice and mice with disrupted retinal waves. We identified several genes that show RGC-type-specific regulation in their expression, including multiple neuropeptides and ion channels. However, wave-dependent changes in the transcriptome were more subtle than developmental changes, indicating that spontaneous activity-dependent molecular changes in retinal ganglion cells are not primarily manifested at the transcriptomic level.

neuroscience↗

bioRxiv2022

Cellular Mechanisms Underlying Embryonic Retinal Waves

Spontaneous activity is a hallmark of developing neural systems. In the retina, spontaneous activity comes in the form of retinal waves, comprised of three stages persisting from embryonic day 16 (E16) to eye opening at postnatal day 14 (P14). Though postnatal retinal waves have been well characterized, little is known about the spatiotemporal properties or the mechanisms mediating embryonic retinal waves, designated Stage 1 waves. Using a custom-built macroscope to record spontaneous calcium transients from whole embryonic retinas, we show that Stage 1 waves are initiated at several locations across the retina and propagate across finite regions of a broad range of areas. A gap junction antagonist, meclofenamic acid, reduced the frequency and size of Stage 1 waves but did not abolish them. The general nAChR antagonist, hexamethonium blocked Stage 1 waves, while they persisted in the presence of 4{beta}2 nAChR antagonist dihydro-{beta}-erythroidine, indicating that the spatiotemporal properties of Stage 1 waves are mediated by a complex circuitry involving subtypes of nAChRs and gap junctions. Stage 1 waves in mice lacking the {beta}2 subunit of the nAChRs ({beta}2-nAChR-KO) were reduced, but in contrast to WT mice, they persisted in the hexamethonium and were completely blocked by meclofenamic acid. To assay the impact of Stage 1 waves on retinal development, we compared the spatial distribution of a subtype of retinal ganglion cells, intrinsically photosensitive retinal ganglion cells (ipRGCs) in WT and {beta}2-nAChR-KO mice. We found that the developmental decrease of ipRGC density is preserved between WT and {beta}2-nAChR-KO mice, indicating that processes regulating ipRGC distribution are not influenced by spontaneous activity.

neuroscience↗

bioRxiv2022

Distinct Inhibitory Pathways Control Velocity and Directional Tuning in the Retina

The sensory periphery is responsible for detecting ethologically relevant features of the external world, using compact, predominantly feedforward circuits. Visual motion is a particularly prevalent sensory feature, the presence of which can be a signal to enact diverse behaviors ranging from gaze stabilization reflexes, to predator avoidance or prey capture. To understand how the retina constructs the distinct neural representations required for these diverse behaviors, we investigated two circuits responsible for encoding different aspects of image motion: ON and ON-OFF direction selective ganglion cells (DSGCs). Using a combination of 2-photon targeted whole cell electrophysiology, pharmacology, and conditional knockout mice, we show that distinct inhibitory pathways independently control tuning for motion velocity and motion direction in these two cell types. We further employ dynamic clamp and numerical modeling techniques to show that asymmetric inhibition provides a velocity-invariant mechanism of directional tuning, despite the strong velocity dependence of classical models of direction selectivity. We therefore demonstrate that invariant representations of motion features by inhibitory interneurons act as computational building blocks to construct distinct, behaviorally relevant signals at the earliest stages of the visual system.

neuroscience↗

bioRxiv2021

Excitatory neurotransmission activates compartmentalized calcium transients in Müller glia without affecting lateral process motility

Neural activity has been implicated in the motility and outgrowth of glial cell processes throughout the central nervous system. Here we explore this phenomenon in Muller glia, which are specialized radial astroglia that are the predominant glial type of the vertebrate retina. Muller glia extend fine filopodia-like processes into retinal synaptic layers, in similar fashion to brain astrocytes and radial glia which exhibit perisynaptic processes. Using two-photon volumetric imaging, we found that during the second postnatal week, Muller glial processes were highly dynamic, with rapid extensions and retractions that were mediated by cytoskeletal rearrangements. During this same stage of development, retinal waves led to increases in cytosolic calcium within Muller glial lateral processes and stalks. These comprised distinct calcium compartments, distinguished by variable participation in waves, timing, and sensitivity to an M1 muscarinic acetylcholine receptor antagonist. However, we found that motility of lateral processes was unaffected by the presence of pharmacological agents that enhanced or blocked wave-associated calcium transients. Finally, we found that mice lacking normal cholinergic waves in the first postnatal week also exhibited normal Muller glial process morphology. Hence, outgrowth of Muller glial lateral processes into synaptic layers is determined by factors that are independent of neuronal activity.

neuroscience↗

bioRxiv2019

Visual experience instructs dendrite orientation but is not required for asymmetric wiring of the retinal direction selective circuit.

Changes in dendritic morphology in response to activity have long been thought to be a critical component of how neural circuits develop to properly encode sensory information. Here we report the impact of dark-rearing on the dendritic morphology and function of a retinal ganglion cell type, a ventral-preferring direction-selective ganglion cell (vDSGC). vDSGCs have asymmetric dendrites oriented along their preferred direction. We found that, at eye opening, vDSGC dendrites are not yet ventrally oriented, and that, surprisingly, dark-rearing prevents ventral orientation of vDSGC dendrites. Despite their dramatic change in dendritic morphology, vDSGCs in dark-reared mice maintain ventral directional preference. Direction selective tuning in dark-reared mice is mediated by asymmetric inhibition, as observed in vDSGCs of normally reared animals. Hence, we postulate that dendritic form follows proper circuit function, where dendritic orientation is refined over the course of development and is dependent on structured visual experience following eye opening.

neuroscience↗