From a by-stander to an influencer: How microglia adapt to altered environments and influence neuronal activity
Microglia, traditionally classified as immune-responsive, adjust synaptic connections during development and disease. However, their role in the adult nervous system has been mostly diminished to an observer. In my research group, we are interested in how microglia are involved in establishing and maintaining accurate neuronal circuit function in the retina and in the visual cortex. In my talk, I will introduce our strategies how to decipher the microglia’s functional identity and how this information guided us to microglia enabled extracellular matrix remodeling and reinstatment of juvenile-like plasticity in the adult brain.
Young IBRO NextInNeuro Webinar - The retinal basis of colour vision: from fish to humans
Colour vision is based on circuit-level comparison of the signals from spectral distinct types of photoreceptors. In our own eyes, the presence of three types of cones enable trichromatic colour vision. However, many phylogenetically ‘older’ vertebrates have four or more cone types, and in almost all their cases the circuits that enable tetra- or possibly even pentachromatic colour vision are not known. This includes the majority of birds, reptiles, amphibians, and bony fish. In the lab we study neuronal circuits for colour vision in non-mammalian vertebrates, with a focus on zebrafish, a tetrachromatic surface dwelling species of teleost. I will discuss how in the case of zebrafish, retinal colour computations are implemented in a fundamentally different, and probably much more efficient way compared to how they are thought to work in humans. I will then highlight how these fish circuits might be linked with those in mammals, possibly providing a new way of thinking about how circuits for colour vision are organized in vertebrates.
Predicting the future from the past: Motion processing in the primate retina
The Manookin lab is investigating the structure and function of neural circuits within the retina and developing techniques for treating blindness. Many blinding diseases, such as retinitis pigmentosa, cause death of the rods and cones, but spare other cell types within the retina. Thus, many techniques for restoring visual function following blindness are based on the premise that other cells within the retina remain viable and capable of performing their various roles in visual processing. There are more than 80 different neuronal types in the human retina and these form the components of the specialized circuits that transform the signals from photoreceptors into a neural code responsible for our perception of color, form, and motion, and thus visual experience. The Manookin laboratory is investigating the function and connectivity of neural circuits in the retina using a variety of techniques including electrophysiology, calcium imaging, and electron microscopy. This knowledge is being used to develop more effective techniques for restoring visual function following blindness.
Natural visual stimuli for mice
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.
Towards hybrid models of retinal circuits - integrating biophysical realism, anatomical constraints and predictive performance
Visual processing in the retina has been studied in great detail at all levels such that a comprehensive picture of the retina's cell types and the many neural circuits they form is emerging. However, the currently best performing models of retinal function are black-box CNN models which are agnostic to such biological knowledge. Here, I present two of our recent attempts to develop computational models of processing in the inner retina, which both respect biophysical and anatomical constraints yet provide accurate predictions of retinal activity
The subcellular organization of excitation and inhibition underlying high-fidelity direction coding in the retina
Understanding how neural circuits in the brain compute information not only requires determining how individual inhibitory and excitatory elements of circuits are wired together, but also a detailed knowledge of their functional interactions. Recent advances in optogenetic techniques and mouse genetics now offer ways to specifically probe the functional properties of neural circuits with unprecedented specificity. Perhaps one of the most heavily interrogated circuits in the mouse brain is one in the retina that is involved in coding direction (reviewed by Mauss et al., 2017; Vaney et al., 2012). In this circuit, direction is encoded by specialized direction-selective (DS) ganglion cells (DSGCs), which respond robustly to objects moving in a ‘preferred’ direction but not in the opposite or ‘null’ direction (Barlow and Levick, 1965). We now know this computation relies on the coordination of three transmitter systems: glutamate, GABA and acetylcholine (ACh). In this talk, I will discuss the synaptic mechanisms that produce the spatiotemporal patterns of inhibition and excitation that are crucial for shaping directional selectivity. Special emphasis will be placed on the role of ACh, as it is unclear whether it is mediated by synaptic or non-synaptic mechanisms, which is in fact a central issue in the CNS. Barlow, H.B., and Levick, W.R. (1965). The mechanism of directionally selective units in rabbit's retina. J Physiol 178, 477-504. Mauss, A.S., Vlasits, A., Borst, A., and Feller, M. (2017). Visual Circuits for Direction Selectivity. Annu Rev Neurosci 40, 211-230. Vaney, D.I., Sivyer, B., and Taylor, W.R. (2012). Direction selectivity in the retina: symmetry and asymmetry in structure and function. Nat Rev Neurosci 13, 194-208