Raunak Sinha

Membrane biophysics in the retina: From photons to neuronal function

Our lab studies how biophysical mechanisms shape neural signaling in the retina. 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.

We are interested in how visual signals are generated in the photoreceptors and how they are modified along the downstream retinal circuitry. Photoreceptors convert light into electrical signals through a G protein coupled receptor mediated signaling cascade. We study how photoreceptors differ in their functional properties across types and across the visual field. We are interested in understanding the underlying mechanisms that create this diversity in photoreceptor signaling and in particular the contribution of the phototransduction cascade. Using a combination of single cell electrophysiology, pharmacology and molecular biology, we probe photoreceptor function and dissect the cellular and molecular mechanisms that generate diversity of photoreceptor function.

Signals generated in the photoreceptors are relayed to downstream retinal neurons at two synaptic layers first between the photoreceptor and second order neurons (bipolar cells) and next between the bipolar and retinal output neurons (ganglion cells). These synapses are specialized ribbon-type synapses that are geared for rapid high throughput release of neurotransmitters and can operate over a broad range of neural inputs. Our lab is interested in understanding how the properties of these synapses differ across retinal neurons which in turn gives rise to the diversity of visual computations across parallel pathways in the retina. These ribbon synapses are also the site of feedback and feedforward inhibitory signals which further regulate the dynamics of neurotransmitter release and signal flow. We utilize electrophysiological recording and optical imaging to assay synaptic and neuronal function. We correlate functional properties with anatomical analysis of synapse distribution on retinal neurons using light and electron microscopy. We use genetic tools to perturb synaptic function and identify molecular mechanisms shaping synaptic computations. This combinatorial approach allows us to dissect the molecular, anatomical and functional diversity of retinal synapses and circuits one element at a time.

A combinatorial approach to study synapses, circuits and retinal function

Our lab utilizes electrophysiology and functional imaging to assay neuronal function in vertebrate retina. We correlate single cell physiology with detailed anatomical analysis using light and electron microscopy. We take advantage of ultrastructural tools like serial block face scanning electron microscope to map connectivity between cell types and construct wiring diagrams. We use genetic and viral tools to perturb cell function, express fluorescent probes and map circuits. This combinatorial approach allows us to dissect the molecular, anatomical and functional diversity of retinal circuits one element at a time.

Lab website

Representative publications:

Baudin J, Angueyra J, Sinha R*, Rieke F. S cone photoreceptors in the primate retina are functionally distinct from L and M cones. eLife. 2019; 8:e39166. (* corresponding author)

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).

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.