Understanding and predicting how nervous systems generate behaviors

As pointed out by the BRAIN Initiative Advisory Committee, the psychiatric illnesses that devastate individual lives and families, and cost society billions of dollars annually, cause their damage by disrupting neural circuits. We use the microscopic nematode Caenorhabditis elegansas a biological breadboard for developing computational algorithms and experimental strategies for understanding and predicting how neural circuits generate behaviors. The sheer complexity of the human brain (over 80,000,000,000 neurons and 100,000,000,000,000 connections) makes understanding its function a formidable challenge. In contrast, the fully mapped C. elegans’s nervous system has only 302 neurons and 7300 connections, making it the closest biological analog to an electronic circuitboard. Despite its relative simplicity compared to humans, C. elegans exhibits many complex behaviors including exploration, social behavior, and learning.

We have prototyped a diverse set of genetically-encoded light and chemical-activated tools for manipulating and perturbing the activity of individual C. elegans neurons. To comprehensively measure behaviors as they change over time, we have developed a software suite for tracking dozens of animals simultaneously for a spectrum of locomotion behaviors. We are using these tools to experimentally test algorithms for reverse-engineering the nervous system. Our goal is that the experimental methods and computational algorithms we develop using C. elegans can be applied to more complex nervous systems, including, ultimately, human patients.

Pokala Lab

Selected Publications

• Jin X, Pokala N, and Bargmann CI. Separate memory formation and retrieval circuits for aversive olfactory imprinting in C. elegans. Cell. Feb 11;164(4):632-643 (2016)
• Gordus AG, Pokala N, Levy S, Flavell SW, and Bargmann CI. Feedback from network states generates variability in a probabilistic olfactory circuit. Cell. Apr 9;161(2):215-27 (2015)
• Pokala N, Liu Q, Gordus A, Bargmann CI. Inducible and titratable silencing of Caenorhabditis elegans neurons in vivo with histamine-gated chloride channels. Proc Natl Acad Sci USA. Feb 18;111(7):2770-5 (2014)
• Flavell SW, Pokala N, Macosko EZ, Albrecht DR, Larsch J, Bargmann CI. Serotonin and the neuropeptide PDF initiate and extend opposing behavioral states in C elegans. Cell. Aug 29;154(5):1023-35 (2013)