Washington University, St. Louis, MO

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Government Grants Promoting Cruelty to Animals

Washington University, St. Louis, MO

LAWRENCE H. SNYDER - Primate Testing - 2006

Grant Number: 5P50MH071616-030004

Our long range goal is to improve our understanding of working memory at the level of individual neurons, and to use this information to develop a model of non-human primate model of disrupted working memory that will shed light on the neural basis of the cognitive deficits in schizophrenia. Schizophrenia patients show structural abnormalities in the dorsolateral prefrontal cortex and the thalamus that may be related to their deficits in working memory. We propose to use both established and novel techniques to investigate normal and disrupted working memory function in these and other areas. In particular, we will use whole-brain functional magnetic resonance imaging in the non-human primate to identify neural circuits involved in working memory and to provide a basis for comparison with analogous human data; we will use single neuron recording in the pulvinar nucleus of the thalamus to characterize its role in working memory; and we will use a novel electrical microstimulation paradigm to disrupt function in prefrontal cortex and thalamus during a context-specific working memory task in order to probe the structure of working memory at a single neuron level. By comparing the animal' s performance with that of schizophrenia patients, we will further our understanding of the role that the targeted areas play in mediating the working memory deficits of the patients. Our choice of target areas is guided by the anatomical data of which explores structural deficits in human schizophrenia patients. Our experimental design is and will continue to be informed by findings , which uses behavioral and imaging techniques to study working memory deficits in patients. Once our model is established, we will directly compare patient behavior with that of our model under identical task conditions. In summary, we believe that our strategy of combining neurophysiological, neuroimaging and behavioral techniques with cross-species comparisons will significantly advance our understanding of the neural bases of both working memory and schizophrenia.

Thesaurus Terms:
brain mapping, prefrontal lobe /cortex, schizophrenia, short term memory, thalamus
brain electrical activity, cognition disorder, disease /disorder model, memory disorder, model design /development, pulvinar thalami
Macaca, behavioral /social science research tag, electrostimulus, functional magnetic resonance imaging, neuropsychological test, single cell analysis

SAINT LOUIS, MO 631304899
Fiscal Year: 2006
Project Start:
Project End:

J Neurophysiol 90: 521-524, 2003

Accuracy of Saccades to Remembered Targets as a Function of Body Orientation in Space

Joshua T. Vogelstein1,2, Lawrence H. Snyder1 and Dora E. Angelaki1,2

Departments of 1Neurobiology and 2Biomedical Engineering, Washington University School of Medicine, St. Louis, Missouri 63110

Submitted 14 February 2003; accepted in final form 19 March 2003

Three Rhesus monkeys were chronically prepared with skull bolts to restrain body motion during experimental trials. A scleral eye coil was surgically implanted under the conjunctiva while animals were under general anesthesia. Each animal was trained to first perform visually guided saccades and subsequently memory-guided saccades for ≥3 mo prior to data collection. All surgical procedures, animal handling and training were in accordance with institutional and National Institutes of Health guidelines.
During experiments, animals were seated in a head-fixed primate chair inside a three-dimensional turntable (Acutronics) equipped with a three-field magnetic system (CNC Engineering). The animals' bodies were secured with shoulder and lap belts, whereas the extremities were loosely fixed to the chair. The chair and magnetic coils could be tilted in a variety of orientations relative to gravity. Saccades were made from four distinct orientations: upright, LSD, RSD, and supine. This configuration allowed dissociation between gravity and head coordinates, although prohibited dissociation between a head- and a body-centered frame of reference. Because the magnetic coils moved with the animal, the recorded eye movements were measured relative to the animals' head and body axes. 

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Rats, mice, birds, amphibians and other animals have been excluded from coverage by the Animal Welfare Act. Therefore research facility reports do not include these animals. As a result of this situation, a blank report, or one with few animals listed, does not mean that a facility has not performed experiments on non-reportable animals. A blank form does mean that the facility in question has not used covered animals (primates, dogs, cats, rabbits, guinea pigs, hamsters, pigs, sheep, goats, etc.). Rats and mice alone are believed to comprise over 90% of the animals used in experimentation. Therefore the majority of animals used at research facilities are not even counted.

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