Motor adaptation is an important factor in the recovery of function following motor deficits associated with neural damage due to stroke, injury or aging. Such motor recovery or adaptation, is instructed by an error signal that is calculated by the brain from the mismatch between the desired movement and the actual movement produced. However, the brain circuits that process specific error signal(s) are not understood. The long-term goal of my research is to identify the neural mechanisms that process error signals to optimize sensory-motor behavior. Understanding these mechanisms and the circuitry underlying them will assist in devising rehabilitation therapies for motor deficits. We have approached our goal by using monkey saccadic eye movements, which provide an ideal model because saccades are precise, use only a few muscles, the associated brainstem neural circuit has been well documented and they can be made to undergo motor adaptation by means of well-established behavioral paradigms. Thus far, we know that complex spike firing in the oculomotor vermis (OMV) encodes motor error and that the OMV is required for adaptation of targeting saccades. Complex spikes in the OMV originate in a part of the inferior olive that receives a projection from the superior colliculus (SC). Previously, we have shown that electrical micro-stimulation of the SC, timed to mimic visual error signals, induces saccade adaptation. Thus, the SC appears to be an important part of the error signal pathway. In this study, we propose three projects to test the involvement of the SC in coding an error signal for saccade adaptation. The first project is directed at determining whether the SC is required for adaptation of targeting saccades. We will inactivate the SC reversibly during which time we predict that the monkey will be unable to adapt its saccades when subjected to a behavioral adaptation paradigm. The second project is directed at identifying correlates in SC visual activity with the visual error signal that drives adaptation. We will look for correlations of SC visual activity wit error size (small errors drive adaptation better than large ones) and with adaptation rate, which decreases as adaptation progresses. The third project will determine whether the SC is also used for adaptation of other types of saccade, including memory-guided, delayed, scanning and express. We will electrically stimulate the SC after one of these different types to mimic an error signal and determine whether, as for targeting saccades, this artificial error causes adaptation. I it does, we will test whether the adaptation transfers to the other types. We anticipate that together the results of these three projects will help establish a previously unsuspected role for the SC in saccade adaptation.

Public Health Relevance

Motor adaptation is important in the recovery from deficits subsequent to neural damage such as stroke, injury or aging. A key to inducing motor adaptation is the error signal, i.e., the mismatch between the desired movement and the actual deficit movement, which drives a motor adaptation that reduces the error. In this project, we will investigate the route and characteristics of the neural mechanism of the error signal by using simian saccadic eye movements.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY023277-05
Application #
9325519
Study Section
Mechanisms of Sensory, Perceptual, and Cognitive Processes Study Section (SPC)
Program Officer
Flanders, Martha C
Project Start
2013-08-01
Project End
2018-07-31
Budget Start
2017-08-01
Budget End
2018-07-31
Support Year
5
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Washington
Department
Veterinary Sciences
Type
Primate Centers
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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