The research in my lab focuses on sensory signal processing, particularly in cases where sensory systems perform at or near the limits imposed by physics. Photon counting in the visual system is a beautiful example. At its peak sensitivity, the performance of the visual system is limited largely by the division of light into discrete photons. This observation has several implications for phototransduction 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, must be reliably transmitted to second-order cells in the retina, and absorption of a single photon by a single rod must produce a noticeable change in the pattern of action potentials sent from the eye to the brain. My approach is to combine quantitative physiological experiments and theory to understand photon counting in terms of basic biophysical mechanisms. Fortunately there is more to visual perception than counting photons. The visual system is very adept at operating over a wide range of light intensities (about 12 orders of magnitude). Over most of this range, vision is mediated by cone photoreceptors. Thus adaptation is paramount to cone vision. Again one would like to understand quantitatively how the biophysical mechanisms involved in phototransduction, synaptic transmission, and neural coding contribute to adaptation.

Age-related Macular Degeneration (AMD) and Retinitis Pigmentosa (RP) are vision disorders caused by loss of rod and cone photoreceptors, but downstream retinal neurons also show physiological and morphological changes, resulting in the emergence of hyperactivity and rhythmic firing in many retinal ganglion cells (RGC). We recently discovered that retinoic acid (RA) is a key signal that triggers hyperactivity and that blockers of RA unmask light responses in RGCs that would otherwise be obscured. Recent work is revealing where in the retina circuit RA initiates functional changes. Moreover, interfering with the RA signaling pathway with drug or gene therapy can improve spatial vision in a mouse model of RP, providing a new strategy for enhancing low vision in human RP and AMD.

The long-term goal of my research is to study the mammalian retina as a model for the central nervous system (CNS) -- to understand how it functions in physiological conditions, how it is formed, how it breaks down in pathological conditions, and how it can be repaired. I have focused on two research themes: 1) Photoreceptor structure, synapse, circuits, and development, 2) Hibernation and metabolic adaptations in the retina and beyond. As the first neuron of the visual system, photoreceptors are vital for photoreception and transmission of visual signals. I am particularly interested in cone photoreceptors, as they mediate our daylight vision with high resolution color information. Diseases affecting cone photoreceptors compromise visual functions in the central macular area of the human retina and are thus most detrimental to our vision. However, because cones are much less abundant compared to rods in most mammals, they are less well studied. We have used the ground squirrel (GS) as a model system to study cone vision, taking advantage of their unique cone-dominant retina. In particular, we have focused on short-wavelength sensitive cones (S-cones), which are not only essential for color vision, but are also an important origin of signals for biological rhythm, mood and cognitive functions, and the growth of the eye during development. We are studying critical cone synaptic structures – synaptic ribbons, the synaptic connections of S-cones, and the development of S-cones with regard to their specific connections. These works will provide knowledge of normal retinal development and function, which can also be extended to the rest of CNS; for example, the mechanisms of synaptic targeting during development. In addition, such knowledge will benefit the development of optimal therapeutic strategies for regeneration and repair in cases of retinal degenerative disease. Many neurodegenerative diseases, including retinal diseases, are rooted in metabolic stress in neurons and/or glial cells. Using the same GS model, we aim to learn from this hibernating mammal, which possesses an amazing capability to adapt to the extreme metabolic conditions during hibernation. By exploring the mechanisms of such adaptation, we hope to discover novel therapeutic tactics for neurodegenerative diseases.

In this talk I will summarize some of our recent unpublished work on spectral coding in the larval zebrafish retina. Combining 2p imaging, hyperspectral stimulation, computational modeling and connectomics, we take a renewed look at the spectral tuning of cone photoreceptors in the live eye. We find that already cones optimally rotate natural colour space in a PCA-like fashion to disambiguate greyscale from "colour" information. We then follow this signal through the retinal layers and ultimately into the brain to explore the major spectral computations performed by the visual system at its consecutive stages. We find that by and large, zebrafish colour vision can be broken into three major spectral zones: long wavelength grey-scale-like vision, short-wavelength prey capture circuits, and spectrally diverse mid-wavelength circuits which possibly support the bulk of "true colour vision" in this tetrachromate vertebrate.

Organisms sense light for purposes that range from recognizing objects to synchronizing activity with environmental cycles. What mechanisms serve these diverse tasks? This seminar will examine the specializations of two cell types. First are the foveal cone photoreceptors. These neurons are used by primates to see far greater detail than other mammals, which lack them. How do the biophysical properties of foveal cones support high-acuity vision? Second are the melanopsin retinal ganglion cells, which are conserved among mammals and essential for processes that include regulation of the circadian clock, sleep, and hormone levels. How do these neurons encode light, and is encoding customized for animals of different niches? In pursuing these questions, a broad goal is to learn how various levels of biological organization are shaped to behavioural needs.

During the course of evolution, a species’ environment shapes its sensory abilities, as individuals with more optimized sensory abilities are more likely survive and procreate. Adaptations to the statistics of the natural environment can be observed along the early visual pathway and across species. Therefore, characterising the properties of natural environments and studying the representation of natural scenes along the visual pathway is crucial for advancing our understanding of the structure and function of the visual system. In the past 20 years, mice have become an important model in vision research, but the fact that they live in a different environment than primates and have different visual needs is rarely considered. One particular challenge for characterising the mouse’s visual environment is that they are dichromats with photoreceptors that detect UV light, which the typical camera does not record. This also has consequences for experimental visual stimulation, as the blue channel of computer screens fails to excite mouse UV cone photoreceptors. In my talk, I will describe our approach to recording “colour” footage of the habitat of mice – from the mouse’s perspective – and to studying retinal circuits in the ex vivo retina with natural movies.