Raunak Sinha, PhD

Research Interests

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.

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.

Selected Publications

• Sinha R*, Hoon M*, Baudin J, Okawa H, Wong RO, Rieke F*. Cellular and Circuit Mechanisms Shaping the Perceptual Properties of the Primate Fovea. Cell. 2017 Jan 26; 168(3):413-426.(*co-correspondence)
• Sinha R, Lee A, Rieke F, Haeseleer F. Lack of CaBP1/caldendrin or CaBP2 leads to altered ganglion cell responses. eNeuro Oct 2016, 2016 Oct 28;3(5).
• Hoon M, Sinha R, Okawa H, Suzuki SC, Hirano AA, Brecha N, Rieke F, Wong RO. Neurotransmission plays contrasting roles in the maturation of inhibitory synapses on axons and dendrites of retinal bipolar cells. PNAS. 2015 Oct 13; 112(41): 12840-5.
• Sinha R, Ahmed S, Jahn R, Klingauf J. Two synaptobrevin molecules are sufficient for vesicle fusion in central nervous system synapses. PNAS. 2011 Aug 23;108(34):14318-23.
• Hua Y*, Sinha R*, Thiel CS*, Schmidt R, Hüve J, Martens H, Hell SW, Egner A, Klingauf J. A readily retrievable pool of synaptic vesicles. Nature Neuroscience. 2011 Jun 12;14(7):833-9. (*equal contribution)
• Hua Y*, Sinha R*, Martineau M, Kahms M, Klingauf J. A common origin of synaptic vesicles undergoing evoked and spontaneous fusion. Nature Neuroscience. 13, 1451–1453 (2010). (*equal contribution)
• Hoon M, Sinha R, Okawa H. Using fluorescent markers to estimate synaptic connectivity in situ. Methods Mol Biol vol. 1538 (2017), Humana Press. ISBN 978-1-4939-6688-2.