Summary: Researchers report a causal connection between running speed and improved associative learning in mice.
Run Faster, Learn Better: Increased Locomotion Boosts Cerebellar Learning in Mice
A team at the Champalimaud Centre for the Unknown in Lisbon, Portugal, has published a study in Nature Neuroscience demonstrating that faster running speeds accelerate and enhance learning in mice.
The researchers initially aimed to link cellular plasticity in the brain to learning, focusing on how circuits in the cerebellum change during acquisition of a motor task. The cerebellum is critical for refining skilled movements and maintaining precise coordination in changing environments, so the team studied a cerebellum-dependent form of associative learning.
Eyeblink Conditioning on a Treadmill
In the experiments, mice were head-fixed on a treadmill and trained in a delay eyeblink conditioning task. A brief sensory cue—such as a light, tone, or whisker vibration—was presented shortly before an air puff to the eye, which normally produces a reflexive blink. Over repeated trials the mice learn to blink in response to the cue, anticipating the air puff. This form of conditioned eyelid closure is known to depend on cerebellar circuits.
Early in the research the team encountered substantial variability in learning and response magnitudes both across animals and across trials within the same animal. That variability initially masked cellular changes they expected to observe. After investigating potential sources, the researchers realized that differences in running ability and running speed were the main contributors to this variability.
Running Speed Drives Learning
When the investigators accounted for individual running speed, the apparent noise in the data largely disappeared. Moreover, when all mice were made to run at the same faster speeds, they showed similar learning curves and reached comparable levels of conditioned eyelid responses. These observations indicated a causal relationship: externally increasing locomotor speed was sufficient to speed up and strengthen learning.
Importantly, the influence of locomotion persisted after learning. If the treadmill speed was reduced once a conditioned response had been learned, the mice performed less well within seconds, showing that ongoing locomotor state modulates expression of the learned behavior on short time scales.
Effect Independent of Sensory Modality
To determine whether the running effect was limited to the visual system, the researchers trained mice using different sensory cues—auditory tones and tactile whisker vibrations—before the air puff. Faster running produced the same enhancement in learning regardless of the sensory modality used for conditioning. This modality-independence suggested that locomotion acts on a neural processing stage downstream of primary sensory areas, pointing the investigators toward cerebellar inputs.
Targeting the Cerebellum with Optogenetics
The team used optogenetics to probe the cerebellum directly. They selectively stimulated mossy fiber inputs—the axons that carry contextual and sensory information into the cerebellum—using light-driven activation. Directly increasing activity in mossy fibers replicated the learning enhancement produced by running, while stimulating targets downstream of mossy fibers did not produce the same modulatory effect.
These experiments indicate that increased activation of the mossy fiber pathway within the cerebellum is a key mechanism by which locomotor activity facilitates associative learning in this task. Substituting prolonged, low-intensity optogenetic stimulation of mossy fibers for physical locomotion was sufficient to boost conditioned responses.
Implications and Caveats
Because the cerebellum is a conserved brain structure across mammals, the authors note the possibility that similar mechanisms could apply to cerebellar forms of learning in humans. The enhancement does not necessarily require locomotion per se; any activity that increases mossy fiber input to the cerebellum might provide an analogous boost to learning. At the same time, the researchers caution that these results do not imply that all forms of learning—or learning that relies on other brain systems—will benefit from increased locomotion in the same way.
The findings also raise everyday questions about movement and cognition. Anecdotally, many people pace or walk while working through difficult problems; this study suggests a neural mechanism by which movement can alter brain state and potentially improve certain types of learning or performance.
About this research
Source: Champalimaud Centre for the Unknown
Publisher: NeuroscienceNews
Image credit: Gil Costa
Original research: “Locomotor activity modulates associative learning in mouse cerebellum” by Catarina Albergaria, N. Tatiana Silva, Dominique L. Pritchett & Megan R. Carey. DOI: 10.1038/s41593-018-0129-x. Published in Nature Neuroscience, April 16, 2018.
Abstract
Behavioral state can strongly influence brain function. This work demonstrates that locomotor activity modulates performance in delay eyeblink conditioning, a cerebellum-dependent associative learning task. In head-fixed mice, increased running speed produced earlier learning onset and trial-by-trial enhancement of conditioned responses. These effects were distinct from changes in arousal and were independent of the sensory modality used for the conditioned stimulus. Optogenetically evoked eyelid responses driven by mossy fiber inputs were positively modulated by ongoing locomotion, whereas stimulation at downstream sites was not. Prolonged, low-intensity optogenetic stimulation of mossy fibers substituted for locomotion and enhanced conditioned responses. Together, the results indicate that locomotor activity promotes delay eyeblink conditioning by increasing activation of the mossy fiber pathway in the cerebellum, revealing a mechanism by which movement can improve associative learning.