Grant Number: 2R01EY012848-06A1
Project Title: Dynamic Basal Ganglia Saccade Networks
PI Information: PROFESSOR ANN M. GRAYBIEL, graybiel@mit.edu 

Abstract: DESCRIPTION (provided by applicant):
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.

Thesaurus Terms:
basal ganglia, neural information processing, oculomotor nuclei, prefrontal lobe /cortex, saccade, visual cortex
learning, neuron, stimulus /response
Macaca mulatta, electrode, performance

Institution: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
77 MASSACHUSETTS AVE
CAMBRIDGE, MA 02139
Fiscal Year: 2006
Department: BRAIN AND COGNITIVE SCIENCES
Project Start: 01-DEC-1999
Project End: 31-MAY-2011
ICD: NATIONAL EYE INSTITUTE
IRG: COG

J Neurophysiol 85: 960-976, 2001; 022-307
The Journal of Neurophysiology Vol. 85 No. 2 February 2001, pp. 960-976

Copyright ©2001 by the American Physiological Society

Neurons in the Thalamic CM-Pf Complex Supply Striatal Neurons With Information About Behaviorally Significant Sensory Events
 
Naoyuki Matsumoto,^1,3 Takafumi Minamimoto,¹ Ann M. Graybiel,² and Minoru Kimura1,^3
 
1Faculty of Health and Sport Sciences, Osaka University, Osaka 560-0043, Japan; ²Department of Brain and Cognitive Sciences, MIT, Cambridge, Massachusetts 02139; and ³Department of Physiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan

Behavioral paradigms
Three macaque monkeys (Macaca fuscata: monkey TM, male, 6.5 kg; monkey AK, female, 6.7 kg; and monkey NA, female, 5.6 kg) were used in this study. The experiments were carried out in compliance with the guidelines for the care and use of experimental animals of the Physiological Society of Japan. Monkeys were trained to sit in a primate chair in a soundproof, electrically shielded room. Ambient illumination was controlled and was dim (monkeys AK and NA; 1.2 cd/m2) or dark (monkey TM; 0.15 cd/m2). A small panel (54 × 23 cm) was placed 50 cm in front of monkeys AK and NA, and 22 cm in front of monkey TM (Fig. 1A). A light-emitting diode (LED) was attached at the center of the panel. The LED could be illuminated (300 cd/m2) under computer control. Before conditioning, click noises made by a solenoid valve, beep sounds (1 kHz, 100 ms duration), flashes of the LED (100 ms duration), and drops of reward water on a spoon in front of the monkey's mouth were presented independently in random order at a fixed time interval (7 s; Fig. 1B). Two tasks were used for behavioral conditioning. One was the stimulus with reward (WR) task, in which the solenoid clicks were followed by reward water delivered 200 ms later. The second task was the stimulus without reward (WOR) task, in which clicks, beeps, and LED flashes were presented without reward (Fig. 1B). The three types of sensory stimuli were presented separately in blocks of 20-30 trials, except in special tests in monkeys TM and AK. In each block of trials, the stimuli occurred at variable intertrial intervals ranging from 5 to 12 s. The stimuli appeared in random order in monkey NA. In monkey NA, to test the somatosensory responses of CM-Pf neurons, tactile stimulation was applied manually to the neck, shoulder, back, or hands by means of a stimulus probe.

The Journal of Neuroscience, December 17, 2003, 23(37):11741-11752

Synchronous, Focally Modulated -Band Oscillations Characterize Local Field Potential Activity in the Striatum of Awake Behaving Monkeys
 
Richard Courtemanche,¹ * Naotaka Fujii,² * and Ann M. Graybiel<sup>2

1</sup>Department of Exercise Science, Concordia University, Montreal, Canada H4B 1R6, and ²Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, and the McGovern Institute for Brain Research, Cambridge, Massachusetts 02139

Subjects and task.
The experiments (33 on each monkey) were performed on two adult female monkeys (Macaca mulatta) (M7, 6 kg; M8, 5 kg) trained previously to perform oculomotor tasks (Courtemanche et al., 2001 ; Fujii and Graybiel, 2001 ; Blazquez et al., 2002 ). Each monkey had an eye coil implanted in one eye to measure eye displacement (Fuchs and Robinson, 1966 ), a head bolt for head fixation, and a recording chamber that could be fitted with a grid for microelectrode placement. The chamber of monkey M7 was aligned with the horizontal plane, centered at stereotypic anterior coordinate A20, and allowed bilateral recordings; the chamber of M8 was implanted on the left side at a 20° angle from the sagittal plane and was centered at A21. The monkeys either rested or performed a visually guided single-saccade task in which the monkey faced a computer screen with a 9 x 9 array of gray dots. The monkey's task was first to fixate the central dot for a period of 700 msec to 1 sec. Feedback to the monkey on her fixation performance was given by turning the center dot from gray to red when eye position was within ±1.25° of the target. After the fixation period, the fixation dot was extinguished and a peripheral dot at a distance of 5° in any of four eccentric locations (0, 90, 180, or 270°) turned red. The monkey's task was to saccade to this location within 400 msec to be rewarded with drops of water 400-800 msec later. Monkeys usually performed 30-40 trials of the task in a block design but sometimes performed longer trial blocks as well. Task parameters were controlled by a computer and custom software. Sessions of quiet rest, in which the monkey simply sat in the chair with head fixed but with eye movements permitted, were also collected for periods of 1-5 min. We noted the occurrence of dozing off periods during data acquisition of the rest condition and identified drowsiness segments off-line by the slow drift in the eye-position recordings.