Neural mechanisms underlying behavioral variability in uni- and multi-sensory contexts

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Project summary/abstract Decisions an animal makes on the basis of multi-sensory input are crucial to its survival. How do neural circuits resolve conflicts to choose among available behaviors while receiving multiple and variable inputs? The navigational behaviors of larval Drosophila form a promising model in which to relate neural activity and behavior. Powerful genetic reagents are available in Drosophila to target nearly arbitrary subsets of 10,000 neurons that make up the larva’s central nervous system (~3, 000 in the brain hemispheres), and an EM reconstruction of this network is almost complete. The larva’s cuticle is semi-transparent, and the entirety of its representative insect brain is optically accessible for in vivo interrogation or manipulation. Even a simple organism like the larva responds variably to seemingly identical stimulus presentations. What is the origin of this variability? This question can be phrased using the language of information theory. If I repeatedly present the same stimulus and observe different behaviors, then the stimulus does not contain full information about the behavior. But directly measuring the activities of the motor neurons that control movement would always allow one to predict the behavior; these neurons have more informationabout the behavior than is present in the stimulus, and this extra information originates somewhere in the nervous system. The task of finding where and how variability originates in larva’s tractable nervous system requires an integrated approach in describing a behavior, identifying which neurons are involved, resolving how circuit activity encodes those behaviors, and discovering the mechanisms generating these neural transformations. To achieve this task, I have developed two techniques of neural circuit interrogation: an optogenetic reverse-correlation behavioral assay that can determine the role of any targeted neuron in decision making, and a first ever two-photon tracking microscope that can record the neural activity as larva freely navigates its sensory environments. In this project, I will decode the circuitry underlying the larva’s navigational responses to uni- and multi-sensory input. In many neurological and psychiatric disorders, such as schizophrenia, autism spectrum disorder, dyslexia, and ADHD, the processing of multisensory information is compromised, perhaps from abnormalities in the neural circuits that are responsible for integrating sensory information. This research will advance our understanding of the neural basis of multisensory decision-making, which will allow us to better understand the defects in information processing that occur during disease.