Homing in on Brain Region That Controls Motor Learning

The dorsal raphe nucleus, a brain region previously implicated in depression, seems to integrate motor memories.

The brain of a larval zebrafish, highlighting neurons that respond to sensory information and behavior. Credit: Nikita Vladimirov

The brain of a larval zebrafish, highlighting neurons that respond to sensory information and behavior. Credit: Nikita Vladimirov and Misha Ahrens

 

When you step from the hard asphalt of a parking lot onto the soft sand of the beach, your brain and motor system quickly adjust your gait to the new terrain. A brain region known as the dorsal raphe nucleus plays an important role in this type of motor learning, according to a zebrafish study by Misha Ahrens, Takashi Kawashima and their collaborators, published in Cell in November 2016.

Just as people keep an even keel when moving from hard to soft surfaces, zebrafish try to maintain a constant swimming speed regardless of water temperature. Colder water dampens the animals’ muscle activity, so that the muscle must be more active to maintain the same pace. To understand how the brain elicits this type of shift, Ahrens’ team analyzed whole-brain activity as zebrafish, harnessed so that their heads remained fixed, viewed a virtual reality scene that made the water appear to move slower or faster. The fish respond by beating their tails more or less, which researchers record. The researchers can mimic changes in water temperature by adjusting motor-sensory gain. For example, they modeled warmer water temperatures with visual cues that made the fish feel as if it were swimming faster. The animals then adjusted their motor commands to maintain a constant swimming speed.

These changes triggered a lasting increase in neural activity in the dorsal raphe nucleus. “If the fish swims multiple times, and every time the world moves more than expected, that neural activity accumulates” — that is, the responses to the visual stimulus during every swim bout are summed together — says Ahrens, a researcher at the Howard Hughes Medical Institute’s Janelia Research Campus in Ashburn, Virginia. “It’s as if the dorsal raphe nucleus is collecting information over time, forming a representation of the expected effect of an action.” According to Ahrens, “the DRN uses this representation of action effectiveness to adjust the animal’s behavior to deal with changes it previously experienced.”

The dorsal raphe nucleus and its primary neuromodulator, serotonin, have previously been implicated in mood disorders, such as depression. Ahrens says he was initially surprised to uncover a role in motor learning. However, motor learning and mood disorders may rely on a similar neural computation —specifically, how these systems evaluate whether an action is successful in achieving its goals. Learned helplessness, for example, is attributed to the animals’ internal belief that their actions have no effect, Ahrens explains. It’s often used as a model of depression in lab animals — the animals are subjected to an unpleasant stimulus, such as electrical shocks, which they can’t avoid. Eventually the animal stops trying to escape — it learns its actions fail to achieve the desired goal. “We think our findings interlink with those observations to start to explain the role of this neuromodulator in a more computational way,” says Ahrens.

 

References:

  1. Kawashima T. et al. Cell 167, 933-946 (2016) PubMed

 

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