Neural Dynamics and Circuit Mechanisms of Decision-Making

Rockefeller University, New York NY

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Abstract

Project Summary / Abstract Decision-making is central to cognition. It relies on an animal's neural circuitry to integrate information from multiple sensory inputs to arrive at an activity state that guides subsequent behavioral choice. Given the derangement of decision-making processes in patients of mental illnesses like schizophrenia, understanding how neural circuits enable decision-making may help to unravel these diseases. The nematode Caenorhabditis elegans offers an excellent model system to study the representation of decision-making in neural activity. It has a simplified nervous system comprising 302 neurons with known connectivity and readily available genetic tools that enable us to monitor and manipulate the activity of single neurons in freely behaving animals. Furthermore, the C. elegans genome contains homologs to genes critical for human nervous system function such as neurotransmitters and ion channels, suggesting that a functional dissection of decision-making in C. elegans could translate to humans in meaningful ways. When C. elegans is exposed to pathogenic bacteria during its first larval stage after hatching, it becomes ?imprinted? to form a lifelong aversive association with the smell of those bacteria. Imprinted adult C. elegans given a choice between the pathogenic bacteria and a harmless kind of bacteria selectively avoid the pathogen, whereas naïve animals do not. Strikingly, the pathogen odor alone remains attractive to imprinted animals, suggesting they make a true decision to avoid pathogen odors by evaluating alternatives. To understand the neuronal and molecular mechanisms that mediate this choice behavior, we propose the following specific aims: 1) to characterize imprinted pathogen avoidance decision behavior by the navigational maneuvers that comprise it; 2) to link activity of key neurons with decision-making behavior using calcium imaging and optogenetics; The completion of these specific aims will yield fundamental insights into the ways circuits represent behavioral outcomes and how learning functionally alters circuits to generate different behaviors from identical sensory inputs. This research plan will provide the ideal training to become an independent researcher studying neural circuits and behavior.