Sengupta Titas

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Differential adhesion regulates neurite placement via a retrograde zippering mechanism

2021-11-16 , Sengupta, Titas , Koonce, Noelle L. , Vázquez-Martínez, Nabor , Moyle, Mark W. , Duncan, Leighton H. , Emerson, Sarah E. , Han, Xiaofei , Shao, Lin , Wu, Yicong , Santella, Anthony , Fan, Li , Bao, Zhirong , Mohler, William A. , Shroff, Hari , Colón-Ramos, Daniel

During development, neurites and synapses segregate into specific neighborhoods or layers within nerve bundles. The developmental programs guiding placement of neurites in specific layers, and hence their incorporation into specific circuits, are not well understood. We implement novel imaging methods and quantitative models to document the embryonic development of the C. elegans brain neuropil, and discover that differential adhesion mechanisms control precise placement of single neurites onto specific layers. Differential adhesion is orchestrated via developmentally regulated expression of the IgCAM SYG-1, and its partner ligand SYG-2. Changes in SYG-1 expression across neuropil layers result in changes in adhesive forces, which sort SYG-2-expressing neurons. Sorting to layers occurs, not via outgrowth from the neurite tip, but via an alternate mechanism of retrograde zippering, involving interactions between neurite shafts. Our study indicates that biophysical principles from differential adhesion govern neurite placement and synaptic specificity in vivo in developing neuropil bundles.

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A genetically encoded tool for reconstituting synthetic modulatory neurotransmission and reconnect neural circuits in vivo

2021-08-09 , Hawk, Josh D. , Wisdom, Elias M. , Sengupta, Titas , Kashlan, Zane D. , Colón-Ramos, Daniel

Chemogenetic and optogenetic tools have transformed the field of neuroscience by facilitating the examination and manipulation of existing circuits. Yet, the field lacks tools that enable rational rewiring of circuits via the creation or modification of synaptic relationships. Here we report the development of HySyn, a system designed to reconnect neural circuits in vivo by reconstituting synthetic modulatory neurotransmission. We demonstrate that genetically targeted expression of the two HySyn components, a Hydra-derived neuropeptide and its receptor, creates de novo neuromodulatory transmission in a mammalian neuronal tissue culture model and functionally rewires a behavioral circuit in vivo in the nematode Caenorhabditis elegans. HySyn can interface with existing optogenetic, chemogenetic and pharmacological approaches to functionally probe synaptic transmission, dissect neuropeptide signaling, or achieve targeted modulation of specific neural circuits and behaviors.