Interdisciplinary PhD in Structural and Computational Biology and Quantitative Biosciences

Raunak Sinha

Assistant Professor, Department of Neuroscience Lab Website raunak.sinha@wisc.edu(608) 265-7836

5505 WI Institutes for Medical Research
1111 Highland Ave
Madison, WI 53705-2275

Education

Ph.D., Max-Planck Institute, Goettingen University, Germany

Visual processing in the retina: How cellular, synaptic and circuit mechanisms shape retinal structure and function

Visual Processing: From photons to visual circuit function

One of the fundamental goals of neuroscience is to understand how information flow through a neural circuit leads to function and ultimately results in meaningful perception and behavior. Barring a few notable exceptions, this relationship between a neural input and behavior is yet to be established for most neural circuits in the brain. The retina provides an ideal model to explore this question for several reasons i) we know a great deal about different elements of the circuit – neuronal subtypes and their wiring, ii) we can control the input signals and directly measure neural responses from different elements of the retinal circuit and iii) it provides a unique opportunity to relate cellular and biophysical mechanisms to circuit-level function and perception/behavior.

Three different types of retinal ganglion cells (color coded) overlaid on the cone photoreceptor array (cyan)
Three different types of retinal ganglion cells (color coded) overlaid on the cone photoreceptor array (cyan)

Our lab studies how cellular, synaptic and circuit-level mechanisms mediate sensory computations in the retina and ultimately lead to visual perception. We pose this question in species that have distinct visual cycles, varied retinal specializations and rely on vision to different degrees. The visual information is parsed into > 20 parallel channels in the retina each of which is specialized to encode a certain feature of the outside visual scene. We study distinct neural circuits in the mammalian retina and ask how each neural circuit is custom-tailored to its function. A remarkable example of this specialization is in the fovea – a tiny region in primate retina that dominates our everyday visual experience, like our ability to read, write text and perceive color with the highest resolution. Our recent work (Sinha et al. Cell 2017) was the first glimpse of how the fovea operates at a cellular and circuit level and how different it is from other regions in the retina. This has opened up a whole new avenue of research about retinal structure and function which gives us a unique opportunity to relate neural mechanisms to centuries worth of beautiful behavioral work on human vision.

We utilize electrophysiological recording and optical imaging to assay neuronal function. We correlate single cell activity with detailed anatomical analysis using light and electron microscopy. We use genetic tools to perturb cell function, express fluorescent probes, map retinal circuits and identify molecular mechanisms shaping cellular processes. This combinatorial approach allows us to dissect the molecular, anatomical and functional diversity of retinal circuits one element at a time.

(A) Image of a neurobiotin-labeled midget ganglion cell in primate retina (left). Electrical responses of a midget ganglion cell to light increments (top: spike raster showing six trials; bottom: inhibitory and excitatory synaptic currents). Immunolabeling showing distribution of excitatory (GluA3 - green) and inhibitory (Gephyrin – red) synaptic proteins on the dendrites of a filled midget ganglion cell (right). (B) Serial block face electron micrographs of primate foveal inner retina showing amacrine cell (red) synapses (asterisk) and bipolar cell (green) ribbon synapses (yellow arrow).
(A) Image of a neurobiotin-labeled midget ganglion cell in primate retina (left). Electrical responses of a midget ganglion cell to light increments (top: spike raster showing six trials; bottom: inhibitory and excitatory synaptic currents). Immunolabeling showing distribution of excitatory (GluA3 – green) and inhibitory (Gephyrin – red) synaptic proteins on the dendrites of a filled midget ganglion cell (right). (B) Serial block face electron micrographs of primate foveal inner retina showing amacrine cell (red) synapses (asterisk) and bipolar cell (green) ribbon synapses (yellow arrow).

Areas of Expertise

  • Membrane & Cellular Biophysics
  • Neuroscience
  • Spectroscopy Microscopy Imaging