Dysfunctions of the basal ganglia have been implicated in extrapyramidal movement disorders such as Parkinson's disease and Huntington's disease, and the basal ganglia are abnormal in some neuropsyctuatric disorders as well. No clear idea has yet emerged, however, about what neural operations are performed in the basal ganglia. Strong evidence suggests that the functions of the basal ganglia must depend heavily on their cortical inputs, because the neocortex provides most of the inputs that the basal ganglia receive. These inputs enter mainly by way of corticostriatal projections to the striatum, and indirectly via the thalamus. The largest outputs of the basal ganglia in turn link these nuclei, through series of synaptic steps, to the motor, promotor and prefrontal cortex. The basal ganglia thus appear. to receive cortical input, process it under the influence of modulatory inputs (for example dopaminergic) and return it to the frontal lobes (and to some brainstem sites). We propose a coordinated series of experiments in monkeys and rats to study cortical-based ganglia linkages. Specifically, we propose to analyze in detail the sensorimotor cortical projections to the striatum. This sensorimotor system has significant advantages for study: the inputs are strong, they can be identified electrophysiologically by recording and microstimulation in the cortex, they can be mapped rigorously with sensitive tracer methods, and they thus can be analyzed in depth to permit stud of the map-transformations that occur between cortex and striatum. Much of the proposed work on this system (AIMS 1,2 and 4) is to be in squirrel monkey, in which we and others have found a distributed, catchy organization of inputs from primary somatosensory and motor cortex to the putamen. We will attempt to determine the rules of organization of these distributed and modular sensorimotor inputs. A series of studies is also proposed in the rat to attempt delineation of striatal cells activated by the sensorimotor cortex. In these experiments we propose (in AIM 3, with follow-up in the squirrel monkey in AIM 4) to use electrical and chemical stimulation of sensorimotor cortex to activate immediatearly genes in striatal neurons. The gene expression will be used as a cellular-level readout of neural ensembles activated by cortical input in the striatum and its output targets, and the pathways necessary for this activation will be determined. With these two complimentary techniques, our goal is to delineate the organization of corticostriatal sensorimotor maps in sufficient detail to gain insight into the functions of the striatum. The significance of this work is twofold. First, it may help uncover the neural substrates of focal and somatotypically distributed banal ganglia movement disorders. Second, it should help identifying what transformations occur in cortical-basal ganglia loops.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS025529-14
Application #
6393409
Study Section
Neurology A Study Section (NEUA)
Program Officer
Sheehy, Paul A
Project Start
1988-07-01
Project End
2002-05-31
Budget Start
2001-06-01
Budget End
2002-05-31
Support Year
14
Fiscal Year
2001
Total Cost
$273,973
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Other Basic Sciences
Type
Other Domestic Higher Education
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Amemori, Ken-Ichi; Amemori, Satoko; Gibson, Daniel J et al. (2018) Striatal Microstimulation Induces Persistent and Repetitive Negative Decision-Making Predicted by Striatal Beta-Band Oscillation. Neuron 99:829-841.e6
Yamanaka, Ko; Hori, Yukiko; Minamimoto, Takafumi et al. (2018) Roles of centromedian parafascicular nuclei of thalamus and cholinergic interneurons in the dorsal striatum in associative learning of environmental events. J Neural Transm (Vienna) 125:501-513
Schwerdt, Helen N; Zhang, Elizabeth; Kim, Min Jung et al. (2018) Cellular-scale probes enable stable chronic subsecond monitoring of dopamine neurochemicals in a rodent model. Commun Biol 1:144
Schwerdt, Helen N; Kim, Min Jung; Amemori, Satoko et al. (2017) Subcellular probes for neurochemical recording from multiple brain sites. Lab Chip 17:1104-1115
Schwerdt, Helen N; Shimazu, Hideki; Amemori, Ken-Ichi et al. (2017) Long-term dopamine neurochemical monitoring in primates. Proc Natl Acad Sci U S A 114:13260-13265
Kalueff, Allan V; Stewart, Adam Michael; Song, Cai et al. (2016) Neurobiology of rodent self-grooming and its value for translational neuroscience. Nat Rev Neurosci 17:45-59
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
Amemori, Ken-ichi; Amemori, Satoko; Graybiel, Ann M (2015) Motivation and affective judgments differentially recruit neurons in the primate dorsolateral prefrontal and anterior cingulate cortex. J Neurosci 35:1939-53
Feingold, Joseph; Gibson, Daniel J; DePasquale, Brian et al. (2015) Bursts of beta oscillation differentiate postperformance activity in the striatum and motor cortex of monkeys performing movement tasks. Proc Natl Acad Sci U S A 112:13687-92

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