An impaired movement due to stroke, injury or aging recovers gradually. Can we speed up the recovery process to achieve the rehabilitation faster? To repair an inaccurate movement, the brain measures the error of the movement, namely the mismatch between the desired movement and the actual dysmetric movement, and changes the movement to minimize the error. This process is called motor adaptation. The speed of adaptation depends on its sensitivity to the error, i.e., the higher the error sensitivity, the faster the adaptation. Theoretical models and neurophysiological studies suggest that the complex spikes of Purkinje cells in the cerebellum encode the error. However, the neurons that deal with the error sensitivity are unknown. Knowing the neuronal mechanisms that control error sensitivity has important implications for setting strategies for the most efficient recovery strategy. In our last grant, we used saccade adaptation as a model system of motor adaptation. When we arranged that each saccade missed its target by a constant error, the adaptation speed decreased gradually during the adaptation session. This indicates that the sensitivity to the constant error decreased during the session. We found that the visual sensitivity of superior colliculus (SC) neurons decreased as the error sensitivity decreased. The visual activity of the SC has been suggested as a source of the complex spikes in the cerebellum, which encode the error of the movement. Therefore, the SC visual activity could provide an error sensitivity signal to the cerebellum. In this next grant period, we propose to examine how the visual activity of SC neurons is shaped to encode the error sensitivity. Many brain structures project to the SC, but one of the best candidates to shape SC activity is the Substantia Nigra pars reticulata (SNr) of the basal ganglia because it inhibits the SC directly. Moreover, because patients with Parkinson?s disease, which affects the basal ganglia, show a slower saccade adaptation, it seems likely that the basal ganglia affect the signal that controls the adaptation speed. To test this hypothesis, we will study the SNr with three complementary approaches. First, we will record SNr activity during saccade adaptation and determine whether any component of SNr discharge is related to error sensitivity. Second, we will determine the effect of SNr inactivation on saccade adaptation. We expect that inactivation will affect the adaptation speed. Third, we will determine the effect that SNr inactivation has on the activity of SC neurons. We expect that SNr inactivation will influence the visual activity of neurons in the rostral SC, which is related to the error sensitivity. We predict that the results of these three projects will reveal a previously unsuspected role for the basal ganglia in controlling the adaptation speed for cerebellar-dependent motor adaptation.

Public Health Relevance

Motor adaptation is important in the recovery from movement dysmetrias that occur as a result of stroke, injury or aging. Motor adaptation to such deficits serves to gradually reduce the mismatch, or error signal, between the desired movement and the actual dysmetric movement. In this project, we will reveal whether the basal ganglia control the sensitivity to the mismatch error during cerebellar-dependent motor adaptation in monkeys and, if so, how it does so.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Mechanisms of Sensory, Perceptual, and Cognitive Processes Study Section (SPC)
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Araj, Houmam H
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University of Washington
Schools of Medicine
United States
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Kojima, Yoshiko; Soetedjo, Robijanto (2018) Elimination of the error signal in the superior colliculus impairs saccade motor learning. Proc Natl Acad Sci U S A 115:E8987-E8995
Herzfeld, David J; Kojima, Yoshiko; Soetedjo, Robijanto et al. (2018) Encoding of error and learning to correct that error by the Purkinje cells of the cerebellum. Nat Neurosci 21:736-743
Kojima, Yoshiko; Soetedjo, Robijanto (2017) Selective reward affects the rate of saccade adaptation. Neuroscience 355:113-125
Galvan, Adriana; Stauffer, William R; Acker, Leah et al. (2017) Nonhuman Primate Optogenetics: Recent Advances and Future Directions. J Neurosci 37:10894-10903
El-Shamayleh, Yasmine; Kojima, Yoshiko; Soetedjo, Robijanto et al. (2017) Selective Optogenetic Control of Purkinje Cells in Monkey Cerebellum. Neuron 95:51-62.e4
Herzfeld, David J; Kojima, Yoshiko; Soetedjo, Robijanto et al. (2015) Encoding of action by the Purkinje cells of the cerebellum. Nature 526:439-42
Kojima, Yoshiko; Fuchs, Albert F; Soetedjo, Robijanto (2015) Adaptation and adaptation transfer characteristics of five different saccade types in the monkey. J Neurophysiol 114:125-37
Kojima, Yoshiko; Robinson, Farrel R; Soetedjo, Robijanto (2014) Cerebellar fastigial nucleus influence on ipsilateral abducens activity during saccades. J Neurophysiol 111:1553-63