Photoreceptor deficits appear at eye opening in Rs1 mutant mouse models of X-linked retinoschisis.

X-linked retinoschisis (XLRS) is an early onset degenerative retinal disease characterized by cystic lesions in the middle layers of the retina. These structural changes are accompanied by a loss of visual acuity and decreased contrast sensitivity. XLRS is caused by mutations in the gene Rs1 which encodes the secreted protein Retinoschisin 1.

From 2D slices to a 3D model: Training students in digital microanatomy analysis techniques through a 3D printed neuron project.

The reconstruction of two-dimensional (2D) slices to three-dimensional (3D) digital anatomical models requires technical skills and software that are becoming increasingly important to the modern anatomist, but these skills are rarely taught in undergraduate science classrooms. Furthermore, learning opportunities that allow students to simultaneously explore anatomy in both 2D and 3D space are increasingly valuable. This report describes a novel learning activity that trains students to digitally trace a serially imaged neuron from a confocal stack and to model that neuron in 3D space for 3D printing.

Light drives the developmental progression of outer retinal function.

The complex nature of rod and cone photoreceptors and the light-evoked responsivity of bipolar cells in the mature rodent retina have been well characterized. However, little is known about the emergent light-evoked response properties of the mouse retina and the role light plays in shaping these emergent responses. We have previously demonstrated that the outer retina is responsive to green light as early as postnatal day 8 (P8).

Modeling cholinergic retinal waves: starburst amacrine cells shape wave generation, propagation, and direction bias.

Stage II cholinergic retinal waves are one of the first instances of neural activity in the visual system as they are present at a developmental timepoint in which light-evoked activity remains largely undetectable. These waves of spontaneous neural activity sweeping across the developing retina are generated by starburst amacrine cells, depolarize retinal ganglion cells, and drive the refinement of retinofugal projections to numerous visual centers in the brain. Building from several well-established models, we assemble a spatial computational model of starburst amacrine cell-mediated wave generation and wave propagation that includes three significant advancements.

Retinal organoid light responsivity: current status and future opportunities.

The ability to generate human retinas in vitro from pluripotent stem cells opened unprecedented opportunities for basic science and for the development of therapeutic approaches for retinal degenerative diseases. Retinal organoid models not only mimic the histoarchitecture and cellular composition of the native retina, but they can achieve a remarkable level of maturation that allows them to respond to light stimulation. However, studies evaluating the nature, magnitude, and properties of light-evoked responsivity from each cell type, in each retinal organoid layer, have been sparse.

Ex vivo electroretinograms made easy: performing ERGs using 3D printed components.

Key Points: Rod and cone photoreceptors convert light into electrochemical signals that are transferred to second order cells, initiating image-forming visual processing. Electroretinograms (ERGs) can detect the associated light-induced extracellular transretinal events, allowing for physiological assessment of cellular activity from morphologically intact retinas. We outline a method for economically configuring a traditional patch-clamp rig for performing high signal-to-noise ex vivo ERGs.

Crosstalk: The diversity of melanopsin ganglion cell types has begun to challenge the canonical divide between image-forming and non-image-forming vision.

Melanopsin ganglion cells have defied convention since their discovery almost 20 years ago. In the years following, many types of these intrinsically photosensitive retinal ganglion cells (ipRGCs) have emerged. In the mouse retina, there are currently six known types (M1-M6) of melanopsin ganglion cells, each with unique morphology, mosaics, connections, physiology, projections, and functions.

μ-Opioid Receptor Activation Directly Modulates Intrinsically Photosensitive Retinal Ganglion Cells.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) encode light intensity and trigger reflexive responses to changes in environmental illumination. In addition to functioning as photoreceptors, ipRGCs are post-synaptic neurons in the inner retina, and there is increasing evidence that their output can be influenced by retinal neuromodulators. Here we show that opioids can modulate light-evoked ipRGC signaling, and we demonstrate that the M1, M2 and M3 types of ipRGCs are immunoreactive for μ-opioid receptors (MORs) in both mouse and rat.

Where You Cut Matters: A Dissection and Analysis Guide for the Spatial Orientation of the Mouse Retina from Ocular Landmarks.

Accurately and reliably identifying spatial orientation of the isolated mouse retina is important for many studies in visual neuroscience, including the analysis of density and size gradients of retinal cell types, the direction tuning of direction-selective ganglion cells, and the examination of topographic degeneration patterns in some retinal diseases. However, there are many different ocular dissection methods reported in the literature that are used to identify and label retinal orientation in the mouse retina. While the method of orientation used in such studies is often overlooked, not reporting how retinal orientation is determined can cause discrepancies in the literature and confusion when attempting to compare data between studies.

Melanopsin Retinal Ganglion Cells Regulate Cone Photoreceptor Lamination in the Mouse Retina.

Newborn neurons follow molecular cues to reach their final destination, but whether early life experience influences lamination remains largely unexplored. As light is among the first stimuli to reach the developing nervous system via intrinsically photosensitive retinal ganglion cells (ipRGCs), we asked whether ipRGCs could affect lamination in the developing mouse retina. We show here that ablation of ipRGCs causes cone photoreceptors to mislocalize at different apicobasal positions in the retina.

A novel map of the mouse eye for orienting retinal topography in anatomical space.

Functionally distinct retinal ganglion cells have density and size gradients across the mouse retina, and some degenerative eye diseases follow topographic-specific gradients of cell death. Hence, the anatomical orientation of the retina with respect to the orbit and head is important for understanding the functional anatomy of the retina in both health and disease. However, different research groups use different anatomical landmarks to determine retinal orientation (dorsal, ventral, temporal, nasal poles).

Functional Assessment of Melanopsin-Driven Light Responses in the Mouse: Multielectrode Array Recordings.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) are a special subset of retinal output neurons capable of detecting and responding to light via a unique photopigment called melanopsin. Melanopsin activation is essential to a wide array of physiological functions, especially to those related to non-image-forming vision. Since ipRGCs only constitute a very small proportion of retinal ganglion cells, targeted recording of melanopsin-driven responses used to be a big challenge to vision researchers.

The Development of Mid-Wavelength Photoresponsivity in the Mouse Retina.

Purpose: Photoreceptors in the mouse retina express much of the molecular machinery necessary for phototransduction and glutamatergic transmission prior to eye opening at postnatal day 13 (P13). Light responses have been observed collectively from rod and cone photoreceptors via electroretinogram recordings as early as P13 in mouse, and the responses are known to become more robust with maturation, reaching a mature state by P30. Photocurrents from single rod outer segments have been recorded at P12, but no earlier, and similar studies on cone photoreceptors have been done, but only in the adult mouse retina.

The M5 Cell: A Color-Opponent Intrinsically Photosensitive Retinal Ganglion Cell.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) combine direct photosensitivity through melanopsin with synaptically mediated drive from classical photoreceptors through bipolar-cell input. Here, we sought to provide a fuller description of the least understood ipRGC type, the M5 cell, and discovered a distinctive functional characteristic-chromatic opponency (ultraviolet excitatory, green inhibitory). Serial electron microscopic reconstructions revealed that M5 cells receive selective UV-opsin drive from Type 9 cone bipolar cells but also mixed cone signals from bipolar Types 6, 7, and 8.

Melanopsin ganglion cell outer retinal dendrites: Morphologically distinct and asymmetrically distributed in the mouse retina.

A small population of retinal ganglion cells expresses the photopigment melanopsin and function as autonomous photoreceptors. They encode global luminance levels critical for light-mediated non-image forming visual processes including circadian rhythms and the pupillary light reflex. There are five melanopsin ganglion cell subtypes (M1-M5).

A subset of ipRGCs regulates both maturation of the circadian clock and segregation of retinogeniculate projections in mice.

The visual system consists of two major subsystems, image-forming circuits that drive conscious vision and non-image-forming circuits for behaviors such as circadian photoentrainment. While historically considered non-overlapping, recent evidence has uncovered crosstalk between these subsystems. Here, we investigated shared developmental mechanisms.

Dorsal root ganglia neurite outgrowth measured as a function of changes in microelectrode array resistance.

Current research in prosthetic device design aims to mimic natural movements using a feedback system that connects to the patient's own nerves to control the device. The first step in using neurons to control motion is to make and maintain contact between neurons and the feedback sensors. Therefore, the goal of this project was to determine if changes in electrode resistance could be detected when a neuron extended a neurite to contact a sensor.

Melanopsin ganglion cells extend dendrites into the outer retina during early postnatal development.

Melanopsin ganglion cells express the photopigment melanopsin and are the first functional photoreceptors to develop in the mammalian retina. They have been shown to play a variety of important roles in visual development and behavior in the early postnatal period (Johnson et al., 2010; Kirkby and Feller, 2013; Rao et al.

Light acts through melanopsin to alter retinal waves and segregation of retinogeniculate afferents.

Waves of correlated activity sweeping across the early postnatal mouse retina promote the segregation and refinement of retinofugal projections. This process has been thought to be spontaneous and unaffected by visual experience. We found, however, that light prolongs spiking during the waves and enhances the segregation of retinogeniculate afferents, and that it did so by activating melanopsin-expressing, intrinsically photosensitive retinal ganglion cells.

Melanopsin-expressing retinal ganglion-cell photoreceptors: cellular diversity and role in pattern vision.

Using the photopigment melanopsin, intrinsically photosensitive retinal ganglion cells (ipRGCs) respond directly to light to drive circadian clock resetting and pupillary constriction. We now report that ipRGCs are more abundant and diverse than previously appreciated, project more widely within the brain, and can support spatial visual perception. A Cre-based melanopsin reporter mouse line revealed at least five subtypes of ipRGCs with distinct morphological and physiological characteristics.

Muscarinic acetylcholine receptor localization and activation effects on ganglion response properties.

Purpose: The activation and blockade of muscarinic acetylcholine receptors (mAChRs) affects retinal ganglion cell light responses and firing rates. This study was undertaken to identify the full complement of mAChRs expressed in the rabbit retina and to assess mAChR distribution and the functional effects of mAChR activation and blockade on retinal response properties.

Methods: RT-PCR, Western blot analysis, and immunohistochemistry were used to identify the complement and distribution of mAChRs in the rabbit retina.

Nicotinic acetylcholine receptor expression by directionally selective ganglion cells.

Acetylcholine (ACh) enhances the preferred direction responses of directionally selective ganglion cells (DS GCs; Ariel & Daw, 1982; Ariel & Adolph, 1985) through the activation of nicotinic acetylcholine receptors (nAChRs; Ariel & Daw, 1982; Massey et al., 1997; Kittila & Massey, 1997). DS GCs appear to express at least two types of nAChRs, those that are sensitive to the partially subtype-specific antagonist methyllycaconitine (MLA), and those that are MLA-insensitive (Reed et al.