Abstract: As animals navigate their environments, their nervous systems transition between a wide range of internal states that influence how sensory information is processed and how behaviors are generated. These states of arousal, motivation, and mood can persist for hours, play a central role in organizing human behavior, and are commonly disrupted in psychiatric disease. Although virtually all animals organize their behavioral outputs in this state-like fashion, the neural mechanisms that underlie the generation of these states remain poorly understood. In this talk, I will present our progress in deciphering neural mechanisms that generate these states, with a focus on the involvement of the distributed neuromodulatory systems that control the brain’s state. Our studies are being performed in the nematode C. elegans, where we can apply cell-specific genetic tools to monitor and perturb neurons throughout a nervous system whose ground-truth connectivity is known. By studying how this organism switches between a range of distinct behavioral states, we have uncovered mechanisms of behavioral state generation that bridge scales of analysis: identifying molecular mechanisms that allow the gut to signal to the brain to activate neuromodulatory systems; defining how neuromodulator release alters ongoing neural circuit dynamics and behavior; and constructing computational models that relate brain-wide neural activity to state-dependent behaviors. We envision that these studies will ultimately reveal fundamental principles of neural circuit function that will generalize across animals.
MIT