Lagging or Leading? Linking Substantia Nigra Activity to Spontaneous Motor Sequences

Behaviors are sequences of actions that are executed in the proper order and correct setting to achieve a goal.  Action sequences and their association with the specific environmental contexts in which they are beneficial can be hardwired, as in the case of innate behaviors, or learned and flexible, as in the case of adaptive responses to changing surroundings.  Every animal must constantly survey its environment and internal motivational state to choose the most contextually-appropriate behavior to execute.  However, little is known regarding how neural circuits store action sequences, trigger the execution of a specific action sequence, and signal the transition from one action element to the next.  Here we propose to use novel methods to quantitatively break down spontaneous and goal-oriented behaviors of mice into their constituent parts, which we call behavioral “syllables.”  We will combine this approach with recordings and perturbations of neural activity to characterize the neural circuits that trigger these syllables and string them together into complex behaviors.  Our analysis will focus on the basal ganglia, a conserved brain region whose dysfunction underlies many disorders of behavioral initiation, sequencing or termination in humans. This work will shed light on the mechanisms used by the brain to create self-generated and goal-oriented patterns of action, and yield important clues about how the links between neural activity and action are altered during disease.