Discovering repeating neural motifs representing sequenced behavior

  • Awardees
  • Bernardo Sabatini, M.D., Ph.D. Harvard University
  • Sandeep Robert Datta, M.D., Ph.D. Harvard University
  • Liam Paninski, Ph.D. Columbia University
  • Naoshige Uchida, Ph.D. Harvard University

Imagine a tennis player hitting a forehand, but in slow-motion: There is anticipatory footwork, alignment of the body, preparation of the racquet, the wind-up and swing of the arm, final adjustments as the ball approaches, contact and a follow-through. Sports coaches and players intuitively learn and divide this complex behavior into discrete steps. Players will drill the footwork, the swing and the follow-through separately. This general principle — that an action can be divided into a series of steps — holds true for any movement we do. However, the smallest meaningful units of behavior remain a mystery. Taking inspiration from linguists, who view spoken words as syllables that can be infinitely recombined, we seek to discover the ‘syllables’ of behavior — and the patterns of brain activity that generate them. We will take advantage of new technology to automatically track the movements and body position of a mouse as it forages around its cage and performs tasks. At the same time, we will monitor the activity of a brain region called the striatum, which is involved in rewards, movements and cognition. Using a new class of mathematical models that do not make many assumptions about how behavior is organized, we will deconstruct the mouse’s normal behavior into motifs, or syllables, and correlate those with brain activity. The striatum is especially interesting to monitor because it receives inputs from the brain’s dopamine system. Recent work suggests that the dopamine system initiates the switch from one behavior to another, providing the basis for how syllables are recombined to create an infinite repertoire of behavior. Our results not only will illuminate how a laboratory mouse behaves but might one day even explain how a professional tennis player hits a forehand.

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