Molecular Neurobiology Laboratory
A central challenge in neuroscience is to understand how neural circuits in the brain transform environmental stimuli into appropriate behavioral outputs. Identification and functional characterization of each neuron within a circuit remains technically challenging in complex vertebrate brains, but invertebrate organisms offer the advantage of simpler, smaller nervous systems that nonetheless produce diverse and robust behaviors.
The nematode C. elegans provides a unique opportunity to study genes, neurons and neural circuit functions in the whole animals. Removal of food odors activates AWC chemosensory neurons and induces a locomotory search program. We apply a combination of genetics, functional imaging and behavioral analysis to study how this circuit regulates behavior.
We are also interested in extending these studies to the zebrafish larval model.
Video: Movie showing AWC calcium responses to removal of odor stimulus at 10 sec. The images are false colored such that violet indicates low fluorescence and red and white indicate high fluorescence.
"Our brains respond to changes in our environment with an almost infinite repertoire of behaviors. I am interested in understanding how neural circuits sense and process information to generate behaviors."
Our brain contains roughly 100 billion cells, each connected through thousands of contact points, adding up to at least a quarter of a million miles of wiring—enough to reach from here to the moon. This marvel of evolutionary engineering allows us to navigate an ever-changing environment, to learn and to remember, but its stunning complexity makes it difficult to trace how information travels from one neuron to another. The Chalasani lab uses the nematode Caenorhabditis elegans (C. elegans), as a model to understand how neural circuits transform sensory input into behaviors. Despite its simplicity, C. elegans displays a number of sophisticated behaviors, making it an ideal model to explore how a simple, well-defined nervous system is able to integrate information from multiple sensory neurons and remember it for long periods of time.
The worms spend about 15 minutes searching for food when they are moved from a plate with food to a food-free plate. The duration of this search time is a function of the quality of the food and the amount of time they have spent feeding on it before being moved. The worms are able to learn the size of a food patch they were growing on and remember it for at least one hour. Chalasani and his team have localized the spatial memory to a pair of interneurons and identified a crucial role for dopamine signaling in executing this behavior.
C. elegans neural circuits integrate multiple sensory inputs to generate complex behaviors. Chalasani has identified that sensory neurons use neuropeptides (small signaling molecules) to communicate information about the identity and strength of the sensory stimuli to the rest of the nervous system. Neuropeptide signaling represents a new approach for coding sensory information in the brain.
He and his group have also observed an interesting predator-prey relationship between C. elegans and a larger worm called Pristionchus pacificus. They found that C. elegans uses three previously undefined sensory neurons to detect and avoid predators and their secretions. Surprisingly, pre-treating the worm with human anti-anxiety drugs attenuates its response to the predator.
In the future, Chalasani plans to extend his lab's studies to zebrafish larvae to test whether vertebrate and invertebrate circuits use similar mechanisms to process information, hoping to gain new insight into how the human brain functions.
From left to right:
Eunice Lau, Kevin Curran, Sarah Leinwand, Shrek Chalasani, Stuart Ibsen, Laura Hale, Adam Calhoun, Ada Tong and Bryan Arias
Salk Institute Research
Sharpee T.O., Calhoun A.J., Chalasani S.H. Information theory of adaptation in neurons, behavior, and mood. Curr Opin Neurobiol. 2014 Apr; 25C:47-53. DOI: 10.1016/j.conb.2013.11.007. Epub 2013 Dec 14. Review.
Lau H.E. and Chalasani, S.H. (2014) Divergent and convergent roles for insulin-like peptides in the worm, fly and mammalian nervous systems. Invert. Neurosci. PMID: 24395463.
Joens, M.S., Huynh, C., Kasuboski, J.M., Ferranti, D., Sigal, Y.J., Zeitvogel, F., Obst, M., Burkhardt, C.J., Curran, K.P., Chalasani, S.H., Stern, L.A., Goetze, B., Fitzpatrick, J.A. (2013) Helium Ion Microscopy (HIM) for the imaging of biological samples at sub-nanometer resolution. Sci. Rep.DOI: 10.1038/srep03514.
Leinwand, S.G. and Chalasani, S.H. (2013). Neuropeptide signaling remodels chemosensory circuit composition in Caenorhabditis elegans. Nature Neuroscience. DOI: 10.1038/nn.3511.
Curran, K.P. and Chalasani, S.H. (2012). Serotonin circuits and anxiety: what can invertebrates teach us? Invert Neurosci. DOI 10.1007/s10158-012-0140-y.
Leinwand, S.G. and Chalasani, S.H. Olfactory networks: from sensation to perception. Curr. Opin in Genet. & Dev.21, 1-6 (2011).
Chalasani, S.H., Kato, S., Albrecht, D.R., Nakagawa, T., Abbot, L.F., and Bargmann, C.I. Neuropeptide feedback modifies odor-evoked dynamics in C.elegans olfactory neurons. Nature Neuroscience 13,615-621 (2010).
Tian, L., Hires, S.A., Mao, T., Huber, D., Chiappe, M.E., Chalasani, S.H., Petreanu, L., Akerboom, J., Schreiter, E.R., Bargmann, C.I., Jayaraman, V., Svoboda, K., and Looger, L.L. Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators. Nature Methods 6, 875-881 (2009).
Macosko, E.Z., Pokala, N., Feinberg, E.H., Chalasani, S.H., Butcher, R.A., Clardy, J., and Bargmann, C.I. A hub-and-spoke circuit drives pheromone attraction and social behaviour in C.elegans. Nature 458, 1171-1175 (2009).
Tsunozaki, M., Chalasani, S.H., and Bargmann, C.I. A behavioral switch: cGMP and PKC signaling in olfactory neurons reverses odor preference in C. elegans. Neuron 59, 959-971 (2008).
Chalasani, S.H., Chronis, N., Tsunozaki, M., Gray, J.M., Ramot, D., Goodman, M.B., and Bargmann, C.I. Dissecting a neural circuit for olfactory behaviour in Caenorhabditis elegans. Nature 450, 63-70 (2007).
Chalasani, S.H.*, Sabol, A.*, Xu, H., Gyda, M.A., Rasband, K., Granato, M., Chien, C.-B., and Raper, J.A. Stromal cell-derived factor (SDF-1) antagonizes Slit/Robo signaling in vivo. * Equal contribution. J. Neuroscience 27, 973-980 (2007).
Kreibich, T.A.*, Chalasani, S.H.*, and Raper, J.A. The neurotransmitter glutamate reduces the axonal responsiveness to multiple repellents through the activation of mGluR1. * Equal contribution. J. Neuroscience 24, 7085-7095 (2004).
Vatamaniuk O.K., Mari S., Lang A., Chalasani S.H., Demkiv L.O., Rea P.A. Phytochelatin synthase, a dipeptidyltransferase that undergoes multisite acylation with gamma-glutamylcysteine during catalysis: stoichiometric and site-directed mutagenic analysis of arabidopsis thaliana PCS1-catalyzed phytochelatin synthesis. J Biol Chem. 2004 May 21;279(21):22449-60. Epub 2004 Mar 5.
Chalasani, S.H., Baribaud, F., Coughlan, C.M., Sunshine, M.J., Lee, V.M.Y., Doms, R.W., Littman, D.R., and Raper, J.A. The chemokine Stromal cell-Derived Factor-1 promotes the survival of embryonic retinal ganglion cells. J. Neuroscience 23, 4601-4612 (2003).
Chalasani, S.H., Sabelko, K.A., Sunshine, M.J., Littman, D.R., and Raper, J.A. The chemokine, SDF-1, reduces the effectiveness of multiple axonal repellents and is required for normal pathfinding. J. Neuroscience 23, 1360-1371 (2003).
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