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Science – Movement

Techniques

  • Complex Behavioral Tasks in Headfixed Mice
  • Neurosurgery
  • Fiber Photometry
  • Optogenetics
  • Multi-site Electrophysiology
  • Computational Modeling

The ability to move when we want

Patients with Parkinson’s disease classically have difficulty initiating movements. But surprisingly, it’s not all movements that are affected. Patients particularly struggle to initiate movements at will, but they can move in reaction to events in their environments with relative ease. If we could understand why Parkinson’s patients struggle to initiate movements, perhaps we could understand where “free will” comes from in the brain.

Parkinson’s disease results from the death of dopamine neurons, and for this reason we are studying how dopamine neurons and the circuits they are involved in participate in our ability to self-initiate movements. To do so, we teach mice to play a timing game in which they learn to self-initiate movements after a seconds-long delay after an audiovisual cue. We can then ask how the activity of dopamine neurons and their downstream targets is different depending on when animals decide to move relatively early versus late.

Even in healthy animals, dopamine neurons are less active when it takes mice longer to initiate movement. In fact, they control the probability of initiating self-timed movements via an apparent ramp-to-threshold process. Fascinatingly, dopamine signals are predictive of when mice move even before they get the start timing cue–when baseline signals are higher, mice move systematically earlier.

But that’s a little eery. Does the mouse have “free will” after all? Where do these baseline dopamine signals come from? And how do these signals interact with the neural circuits dopamine neurons participate in? We are chasing these questions down with a combination of optogenetics and multi-site electrophysiology and photometry experiments in behaving mice.