Clinical data strongly implicate the basal ganglia, including the striatum, in the control of saccadic eye movements. For example, saccade deficits occur both in Parkinson's disease and in Huntington's disease. Experimental evidence also points to the critical role of the striatum and basal ganglia circuits in oculomotor control. The striatum has prominent saccade-related activity, and this region receives projections from oculomotor-related areas of the neocortex including the frontal eye fields, the supplementary eye fields and the caudal dorsolateral prefrontal cortex. The oculomotor zone of the striatum itself projects to the substantia nigra pars reticulata which in turn projects to, and inhibits the superior colliculus and inhibits saccades thereby. This basal ganglia pathway is used as a prime example of the release functions of the basal ganglia. We propose an experimental program to study in Maccaca mulatta the response properties of the oculomotor striatum and oculomotor cortical areas during learning and subsequent performance of a series of tasks including visually-guided sequential saccade tasks. We have developed chronic, multi-electrode recording methods for use as macaques perform a battery of saccade tasks. We will test 3 hypotheses in 3 Aims.
In Aim 1, we hypothesize that many of the response properties of neurons in the oculomotor zone of the striatum and corresponding cortical regions are built up by experience. We will record during acquisition of a defined set of tasks to test this hypothesis.
In Aim 2, we hypothesize that sequence-selective activity will occur in the basal ganglia as macaques perform reaching tasks. To test this hypothesis, we will train macaques on a touch screen reaching task under ocular fixation.
In Aim 3, we hypothesize that spontaneously produced sequences of saccades will be represented in the brain by sequence-selective activity. We will test these hypotheses by recording from multiple electrodes implanted in the striatum and cortex as macaques perform saccade and arm reaching tasks.
We aim to maximize the usefulness of the data collected for understanding oculomotor control exerted by these highly clinically important pathways in health and disease. The basal ganglia are critical for normal movements including sequential movements. Repetitive movement disorders are a hallmark of basal ganglia dysfunction. Our goal is to illuminate mechanisms disordered in these disabling human conditions.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY012848-10
Application #
7860403
Study Section
Cognitive Neuroscience Study Section (COG)
Program Officer
Araj, Houmam H
Project Start
1999-12-01
Project End
2012-05-31
Budget Start
2010-06-01
Budget End
2012-05-31
Support Year
10
Fiscal Year
2010
Total Cost
$396,533
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Smith, Kyle S; Graybiel, Ann M (2016) Habit formation. Dialogues Clin Neurosci 18:33-43
Graybiel, Ann M; Grafton, Scott T (2015) The striatum: where skills and habits meet. Cold Spring Harb Perspect Biol 7:a021691
Desrochers, Theresa M; Amemori, Ken-ichi; Graybiel, Ann M (2015) Habit Learning by Naive Macaques Is Marked by Response Sharpening of Striatal Neurons Representing the Cost and Outcome of Acquired Action Sequences. Neuron 87:853-68
Feingold, Joseph; Desrochers, Theresa M; Fujii, Naotaka et al. (2012) A system for recording neural activity chronically and simultaneously from multiple cortical and subcortical regions in nonhuman primates. J Neurophysiol 107:1979-95
Desrochers, Theresa M; Jin, Dezhe Z; Goodman, Noah D et al. (2010) Optimal habits can develop spontaneously through sensitivity to local cost. Proc Natl Acad Sci U S A 107:20512-7
Jin, Dezhe Z; Fujii, Naotaka; Graybiel, Ann M (2009) Neural representation of time in cortico-basal ganglia circuits. Proc Natl Acad Sci U S A 106:19156-61
Han, Xue; Qian, Xiaofeng; Bernstein, Jacob G et al. (2009) Millisecond-timescale optical control of neural dynamics in the nonhuman primate brain. Neuron 62:191-8
Graybiel, Ann M (2008) Habits, rituals, and the evaluative brain. Annu Rev Neurosci 31:359-87
Fujii, N; Graybiel, A M (2005) Time-varying covariance of neural activities recorded in striatum and frontal cortex as monkeys perform sequential-saccade tasks. Proc Natl Acad Sci U S A 102:9032-7
Courtemanche, Richard; Fujii, Naotaka; Graybiel, Ann M (2003) Synchronous, focally modulated beta-band oscillations characterize local field potential activity in the striatum of awake behaving monkeys. J Neurosci 23:11741-52

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