Retina

Arno Onken examines transformer models for predicting responses in the retina and visual cortex. These models learn complex neural-response patterns from large datasets and can transfer learned representations between settings, but fitting and interpreting them differs from linear–nonlinear and convolutional approaches. The talk discusses the opportunities and difficulties this creates for understanding sensory processing. It includes ViV1T, a transformer trained on natural movies that revealed previously uncharacterised response properties in mouse primary visual cortex. The work illustrates

…diversity in the mammalian cortex and retina.

A major challenge in sensory systems is to understand how neurons extract information from the natural environment. Models derived from their responses to artificial stimuli often have a hard time to generalize and predict responses to natural scenes. However, models directly learned on the responses to natural scenes can be hard to interpret. To address this issue, we have recently developed an approach where we add small perturbations to natural scenes and measure how these perturbations change neuronal responses, to better understand the features extracted by sensory neurons. I will show se

Reliably identifying cell types is crucial for understanding neural systems (1). However, classifying the neurons recorded in large-scale population recordings into well-defined types remains a challenge. While some methods rely on genetic targeting or anatomy for classification, a functional approach used in sensory systems is to analyze neuronal responses to stimuli that elicit distinguishable responses across different types (2, 3, 4). Yet, previous approaches of this nature have been limited by a restricted set of stimuli and scalability issues, thus preventing comprehensive characterizati

As animals navigate and interact with their environment, the image projected on their retina is constantly moving due to both self-motion and external motion of objects. Thus understanding how the retina processes moving objects is of crucial importance. This task is made difficult by the many non-linearities present in the retinal circuit. Previous works showed that retina ganglion cells extract specific non-linear features from moving objects and send this information to the brain. For example, direction selective cells respond maximally to motion in a ”preferred” direction and not in the

Ultrasound stimulation of the retina was proposed as an alternative to retinal prostheses for visual restoration. Prior works have shown that the retina responds to mechanical stimulation, but no attempt on stimulating an ex vivo retina with a free-standing photoacoustic membrane had yet been made. Here, we report ultrahigh precision stimulation of the retina with optically generated focused ultrasound (OFUS). OFUS is generated with a photoacoustic membrane of embedded carbon nanoparticles in polydimetylsiloxane. Using ex vivo multielectrode array recording and pharmalogical approaches, we inv

Ribbon synapses in the retina provide sustained glutamatergic transmitter release that is controlled by Cav1.4 L-type calcium channels in photoreceptors. In bipolar cells the voltage-gated calcium channels (VGCC) responsible for release are less conclusive. We therefore addressed the VGCCs expressed in mouse rod bipolar cells (RBC). We enriched RBCs by FACS-sorting and quantified mRNA expression levels of Cav1, Cav2 and auxiliary VGCC subunit isoforms, including selected splice variants. Transcript variants of candidate VGCC genes were confirmed in RT-PCR and through screening of RNAseq datase

…Retina may be an attractive source of such markers because it is an accessible part of the CNS (in vivo imaging and electrophysiology). Recent studies indicate pathological alterations in retina of AD patients such as retinal ganglion cell degeneration. Recently, we showed a dysfunction in the glutaminergic photoreceptor synapsis associated with a strong expression of phosphorylated tau proteins (p-tau)

Photoreceptors, the light sensors of the retina, come in two varieties: the light-sensitive rod photoreceptors, which are responsible for night vision, and the cone photoreceptors, which operate at higher light intensities and are responsible for daylight and color vision. These different tasks require specific morphological and molecular adaptations of rod and cone photoreceptors in the processes of transduction and transmission of light signals. Here we present the first deep proteome resource of mouse rod and cone photoreceptors to our knowledge. We have established a method using fluoresce

…The retina is the most accessible area of the CNS system that enables noninvasive monitoring of HD mutation carriers, but we need first to determine how retinal alterations correlate with those of inner brain areas. To this aim, we analyzed the transgenic R6/1 and the knockin zQ175 mouse strains using optical coherence tomography (OCT), gene express

…those affecting the optic nerve and retina. However, the mechanisms underlying visual disturbances in SCA1 remain unclear.Therefore, in this study, we aimed to analyze the retinal cell layers of mice with SCA1.Sixteen eye samples were obtained from 6-month-old mice (8 from SCA1 mice and 8 from wild-type). The volume of the retina, as well as the volume and

The retina, as part of the central nervous system, shows abnormalities in Alzheimer`s disease (AD) and type 2 diabetes (T2D). Importantly, analysis of the retina may provide a non-invasive approach with diagnostic and prognostic value for cognitive decline. In addition, T2D increases risk to suffer AD. Accordingly, we have analyzed structural and functional alterations, by spectral domain optical coherence tomography and electroretinography (ERG) respectively, in the retina from APP/PS1 (AD model), db/db (T2D model) and APP/PS1xdb/db (AD-T2D model) animals at 4 weeks of age, before the onset o

The retina processes and transmits visual signals throughout a defined neuronal circuit to retinal ganglion cells, which project to the visual centers of the brain. Microglia have been shown to fine-tune the neuronal circuitry by pruning functionally weak synapses during brain development. However, we do not know whether microglia have a similar impact on the neuronal circuit of the retina.In mice, microglia invade the developing retina as early as embryonic age (E) 11.5, where they reside in in the emerging outer- (OPL) and inner plexiform layer (IPL) throughout adulthood. Here, we investigat

…photoreceptors and output cells in the retina. Classical efficient coding theory describes how sensory systems can maximize information transmission given such capacity constraints, but it treats all input features equally. Not all inp

…of intrinsically photosensitive retinal ganglion cells (ipRGCs). These are a unique type of retinal ganglion cell that contains the photopigment melanopsin. ipRGCs are the retinal neurons responsible for driving non-imaging forming behaviors and reflexes, such as circadian entrainment and pupil constriction, amongst many others. My lab has recently focused on uncovering the diversity of ipRGCs, their distribution throughout the mammalian retina, and their axon projections in the brain.

Like all neural tissue, the retina has a high metabolic demand, and requires a constant supply of oxygen. Second and third order neurons are supplied by the retinal circulation, whose characteristics are similar to brain circulation. However, the photoreceptor region, which occupies half of the retinal thickness, is avascular, and relies on diffusion of oxygen from the choroidal circulation, whose properties are very different, as well as the retinal circulation. By fitting diffusion models to oxygen measurements made with oxygen microelectrodes, it is possible to understand the relative roles

To maintain a stable and clear image of the world, our eyes reflexively follow the direction in which a visual scene is moving. Such gaze stabilization mechanisms reduce image blur as we move in the environment. In non-primate mammals, this behavior is initiated by ON-type direction-selective ganglion cells (ON-DSGCs), which detect the direction of image motion and transmit signals to brainstem nuclei that drive compensatory eye movements. However, ON-DSGCs have not yet been functionally identified in primates, raising the possibility that the visual inputs that drive this behavior instead ari

…circuit of the mammalian retina. In this talk, I will discuss our recent work on how visual contexts dynamically influence the neural processing of motion signals in the direction-selective circuit in the mouse retina.

The retina is probably the most accessible part of the vertebrate central nervous system. Its computational logic can be interrogated in a dish, from patterns of lights as the natural input, to spike trains on the optic nerve as the natural output. Consequently, retinal circuits include some of the best understood computational networks in neuroscience. The retina is also ancient, and central to the emergence of neurally complex life on our planet. Alongside new locomotor strategies, the parallel evolution of image forming vision in vertebrate and invertebrate lineages is thought to have drive

The science of the retina has reached an interesting stage of completion. There exists now a consensus standard model of this neural system - at least in the minds of many researchers - that serves as a baseline against which to evaluate new claims. The standard model links phenomena from molecular biophysics, cell biology, neuroanatomy, synaptic physiology, circuit function, and visual psychophysics. It is further supported by a normative theory explaining what the purpose is of processing visual information this way. Most new reports of retinal phenomena fit squarely within the standard mode

…clearly evident in the outputs of the retina, which arise from neurons called ganglion cells. Work in our lab has shown that mammalian retinas contain more than a dozen distinct types of ganglion cells. Each type appears to filter the retinal image in a unique way and to relay this processed signal to a specific set of targets in the brain. My students and I are working to understand the meaning of this parallel organization through electrophysiological and anatomical studies. We record from light-responsive ganglio

…is ‘temporally optimised’ by 1) the retina’s circadian clock, and 2) a change in behavioural temporal niche.

…and signal processing in the retina: rod photoreceptors must transduce single photon absorptions with high fidelity, single photon signals in photoreceptors, which are only 0.03 – 0.1 mV, mus

…We use the mouse retina as a model system because it allows us to stimulate the circuit precisely with its natural input, patterns of light, and record its natural output, the spike trains of retinal ganglion cells. We harness the power of genetic manipulations and detailed information about cell types to uncover new circuits and discover their role in visual processing. Our methods include electrophysiology, computational modeling, and circuit tracing using a variety of imaging techniques.