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

In the early stages of retinal development, a form of correlated activity known as retinal waves causes periodic depolarizations of immature retinal ganglion cells (RGCs). Retinal waves are crucial for refining visual maps in the brain's retinofugal targets and for the development of retinal circuits underlying feature detection, such as direction selectivity. Yet, how waves alter gene expression in immature RGCs is poorly understood, particularly at the level of the many distinct types of RGCs that underlie the retina's ability to encode diverse visual features.

Visualizing synaptic pruning in the mammalian brain.

Patterns of spontaneous neuronal activity instruct the refinement of developing brain circuits.

Differential Expression Analysis Identifies Candidate Synaptogenic Molecules for Wiring Direction-Selective Circuits in the Retina.

An organizational feature of neural circuits is the specificity of synaptic connections. A striking example is the direction-selective (DS) circuit of the retina. There are multiple subtypes of DS retinal ganglion cells (DSGCs) that prefer motion along one of four preferred directions.

Unsupervised learning on spontaneous retinal activity leads to efficient neural representation geometry.

Prior to the onset of vision, neurons in the developing mammalian retina spontaneously fire in correlated activity patterns known as retinal waves. Experimental evidence suggests that retinal waves strongly influence the emergence of sensory representations before visual experience. We aim to model this early stage of functional development by using movies of neurally active developing retinas as pre-training data for neural networks.

Mapping the Retina onto the Brain.

Vision begins in the retina, which extracts salient features from the environment and encodes them in the spike trains of retinal ganglion cells (RGCs), the output neurons of the eye. RGC axons innervate diverse brain areas (>50 in mice) to support perception, guide behavior, and mediate influences of light on physiology and internal states. In recent years, complete lists of RGC types (∼45 in mice) have been compiled, detailed maps of their dendritic connections drawn, and their light responses surveyed at scale.

Rejection of inappropriate synaptic partners in mouse retina mediated by transcellular FLRT2-UNC5 signaling.

During nervous system development, neurons choose synaptic partners with remarkable specificity; however, the cell-cell recognition mechanisms governing rejection of inappropriate partners remain enigmatic. Here, we show that mouse retinal neurons avoid inappropriate partners by using the FLRT2-uncoordinated-5 (UNC5) receptor-ligand system. Within the inner plexiform layer (IPL), FLRT2 is expressed by direction-selective (DS) circuit neurons, whereas UNC5C/D are expressed by non-DS neurons projecting to adjacent IPL sublayers.

Circuit 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.

Roles of visually evoked and spontaneous activity in the development of retinal direction selectivity maps.

Detecting the direction of motion underlies many visually guided behaviors, from reflexive eye movements to identifying and catching moving objects. A subset of motion sensitive cells are direction selective - responding strongly to motion in one direction and weakly to motion in other directions. In mammals, direction-selective cells are found throughout the visual system, including the retina, superior colliculus, and primary visual cortex.

The Retinal Basis of Light Aversion in Neonatal Mice.

Aversive responses to bright light (photoaversion) require signaling from the eye to the brain. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) encode absolute light intensity and are thought to provide the light signals for photoaversion. Consistent with this, neonatal mice exhibit photoaversion before the developmental onset of image vision, and melanopsin deletion abolishes photoaversion in neonates.

Distinct inhibitory pathways control velocity and directional tuning in the mouse 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 behaviors, we investigated two circuits responsible for encoding different aspects of image motion: ON and ON-OFF direction-selective ganglion cells (DSGCs).

Müller Glia in Retinal Development: From Specification to Circuit Integration.

Müller glia of the retina share many features with astroglia located throughout the brain including maintenance of homeostasis, modulation of neurotransmitter spillover, and robust response to injury. Here we present the molecular factors and signaling events that govern Müller glial specification, patterning, and differentiation. Next, we discuss the various roles of Müller glia in retinal development, which include maintaining retinal organization and integrity as well as promoting neuronal survival, synaptogenesis, and phagocytosis of debris.

The influence of spontaneous and visual activity on the development of direction selectivity maps in mouse retina.

In mice, retinal direction selectivity is organized in a map that aligns to the body and gravitational axes of optic flow, and little is known about how this map develops. We find direction selectivity maps are largely present at eye opening and develop normally in the absence of visual experience. Remarkably, in mice lacking the beta2 subunit of neuronal nicotinic acetylcholine receptors (β2-nAChR-KO), which exhibit drastically reduced cholinergic retinal waves in the first postnatal week, selectivity to horizontal motion is absent while selectivity to vertical motion remains.

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 Müller glia, which are specialized radial astroglia that are the predominant glial type of the vertebrate retina. Müller glia extend fine filopodia-like processes into retinal synaptic layers, in similar fashion to brain astrocytes and radial glia that exhibit perisynaptic processes.

Dendrite Morphology Minimally Influences the Synaptic Distribution of Excitation and Inhibition in Retinal Direction-Selective Ganglion Cells.

Throughout the nervous system, the organization of excitatory and inhibitory synaptic inputs within a neuron's receptive field shapes its output computation. In some cases, multiple motifs of synaptic organization can contribute to a single computation. Here, we compare two of these mechanisms performed by two morphologically distinct retinal direction-selective ganglion cells (DSGCs): directionally tuned inhibition and spatially offset inhibition.

Visual Experience Influences Dendritic 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. Ventral-preferring direction-selective ganglion cells (vDSGCs) have asymmetric dendrites oriented along their preferred direction, and this has been hypothesized to play a critical role in their tuning. Here we report the surprising result that visual experience is critical for the alignment of vDSGC dendrites to their preferred direction.

The Impact of Steroid Activation of TRPM3 on Spontaneous Activity in the Developing Retina.

In the central nervous system, melastatin transient receptor potential (TRPM) channels function as receptors for the neurosteroid pregnenolone sulfate (PregS). The expression and function of TRPM3 has been explored in adult retina, although its role during development is unknown. We found, during the second postnatal week in mice, TRPM3 immunofluorescence labeled distinct subsets of inner retinal neurons, including a subset of retinal ganglion cells (RGCs), similar to what has been reported in the adult.

Gap Junction Coupling Shapes the Encoding of Light in the Developing Retina.

Detection of ambient illumination in the developing retina prior to maturation of conventional photoreceptors is mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs) and is critical for driving several physiological processes, including light aversion, pupillary light reflexes, and photoentrainment of circadian rhythms. The strategies by which ipRGCs encode variations in ambient light intensity at these early ages are not known. Using unsupervised clustering of two-photon calcium responses followed by inspection of anatomical features, we found that the population activity of the neonatal retina could be modeled as six functional groups that were composed of mixtures of ipRGC subtypes and non-ipRGC cell types.

Light Prior to Eye Opening Promotes Retinal Waves and Eye-Specific Segregation.

Retinal waves are bursts of correlated activity that occur prior to eye opening and provide a critical source of activity that drives the refinement of retinofugal projections. Retinal waves are thought to be initiated spontaneously with their spatiotemporal features dictated by immature neural circuits. Here we demonstrate that, during the second postnatal week in mice, changes in light intensity dictate where and when a subset of retinal waves are triggered via activation of conventional photoreceptors.

The Value of Undergraduate Teaching for Research Scientists.

Teaching undergraduates is part of the academic commitment for many neuroscience faculty. While some scientists view this as a major distraction from research, teaching is of high value, both in training young scientists and for informing one's own scientific investigations.

A Role for Mouse Primary Visual Cortex in Motion Perception.

Visual motion is an ethologically important stimulus throughout the animal kingdom. In primates, motion perception relies on specific higher-order cortical regions. Although mouse primary visual cortex (V1) and higher-order visual areas show direction-selective (DS) responses, their role in motion perception remains unknown.

A Dense Starburst Plexus Is Critical for Generating Direction Selectivity.

Starburst amacrine cell (SAC) morphology is considered central to retinal direction selectivity. In Sema6A mice, SAC dendritic arbors are smaller and no longer radially symmetric, leading to a reduction in SAC dendritic plexus density. Sema6A mice also have a dramatic reduction in the directional tuning of retinal direction-selective ganglion cells (DSGCs).

Motion Vision: Cortical Preferences Influenced by Retinal Direction Selectivity.

A recent study shows that retinal direction selectivity influences a subset of cells in primary visual cortex which respond to the optic flow associated with forward motion, while other cortical direction selective cells perform this computation independently.

Visual Circuits for Direction Selectivity.

Images projected onto the retina of an animal eye are rarely still. Instead, they usually contain motion signals originating either from moving objects or from retinal slip caused by self-motion. Accordingly, motion signals tell the animal in which direction a predator, prey, or the animal itself is moving.