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Srinivasan, Jagan

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Srinivasan

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Jagan

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Srinivasan, Jagan
Author's Publications: search.filters.isAuthorOfPublication.17668136-c9c5-4d7a-83c4-0efbd572f5c9

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    Contrasting responses within a single neuron class enable sex-specific attraction in Caenorhabditis elegans
    (Proceedings of the National Academy of Sciences, 2016) Narayan, Anusha; Venkatachalam, Vivek; Durak, Omer; Reilly, Douglas K.; Bose, Neelanjan; Schroeder, Frank C.; Samuel, Aravi; Srinivasan, Jagan; Sternberg, Paul W.
    Animals find mates and food, and avoid predators, by navigating to regions within a favorable range of available sensory cues. How are these ranges set and recognized? Here we show that male Caenorhabditis elegans exhibit strong concentration preferences for sex-specific small molecule cues secreted by hermaphrodites, and that these preferences emerge from the collective dynamics of a single male-specific class of neurons, the cephalic sensory neurons (CEMs). Within a single worm, CEM responses are dissimilar, not determined by anatomical classification and can be excitatory or inhibitory. Response kinetics vary by concentration, suggesting a mechanism for establishing preferences. CEM responses are enhanced in the absence of synaptic transmission, and worms with only one intact CEM show nonpreferential attraction to all concentrations of ascaroside for which CEM is the primary sensor, suggesting that synaptic modulation of CEM responses is necessary for establishing preferences. A heterogeneous concentration-dependent sensory representation thus appears to allow a single neural class to set behavioral preferences and recognize ranges of sensory cues.
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    Pan-neuronal imaging in roaming Caenorhabditis elegans
    (Proceedings of the National Academy of Sciences, 2015) Venkatachalam, Vivek; Ji, Ni; Wang, Xian-Ling; Clark, Christopher; Mitchell, James; Klein, Mason; Tabone, Christopher; Florman, Jeremy; Ji, Hongfei; Greenwood, Joel S.f.; Chisholm, Andrew; Srinivasan, Jagan; Alkema, Mark; Zhen, Mei; Samuel, Aravi
    We present an imaging system for pan-neuronal recording in crawling Caenorhabditis elegans. A spinning disk confocal microscope, modified for automated tracking of the C. elegans head ganglia, simultaneously records the activity and position of ∼80 neurons that coexpress cytoplasmic calcium indicator GCaMP6s and nuclear localized red fluorescent protein at 10 volumes per second. We developed a behavioral analysis algorithm that maps the movements of the head ganglia to the animal’s posture and locomotion. Image registration and analysis software automatically assigns an index to each nucleus and calculates the corresponding calcium signal. Neurons with highly stereotyped positions can be associated with unique indexes and subsequently identified using an atlas of the worm nervous system. To test our system, we analyzed the brainwide activity patterns of moving worms subjected to thermosensory inputs. We demonstrate that our setup is able to uncover representations of sensory input and motor output of individual neurons from brainwide dynamics. Our imaging setup and analysis pipeline should facilitate mapping circuits for sensory to motor transformation in transparent behaving animals such as C. elegans and Drosophila larva.
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    A Compressed Sensing Framework for Efficient Dissection of Neural Circuits
    (Springer Nature, 2018-12-20) Lee, Jeffrey B.; Yonar, Abdullah; Hallacy, Timothy; Shen, Ching-Han; Milloz, Josselin; Srinivasan, Jagan; Kocabas, Askin; Ramanathan, Sharad
    A fundamental question in neuroscience is how neural networks generate behavior. The lack of genetic tools and unique promoters to functionally manipulate specific neuronal subtypes makes it challenging to determine the roles of individual subtypes in behavior. We describe a compressed sensing-based framework in combination with non-specific genetic tools to infer candidate neurons controlling behaviors with fewer measurements than previously thought possible. We tested this framework by inferring interneuron subtypes regulating the speed of locomotion of the nematode Caenorhabditis elegans. We developed a real-time stabilization microscope for accurate long-term, high-magnification imaging and targeted perturbation of neural activity in freely moving animals to validate our inferences. We show that a circuit of three interconnected interneuron subtypes, RMG, AVB and SIA control different aspects of locomotion speed as the animal navigates its environment. Our work suggests that compressed sensing approaches can be used to identify key nodes in complex biological networks.