The work proposed focuses on interrelated regions of the basal ganglia (striatum and pallidum) and substantia nigra. Diseases of the basal ganglia are debilitating and are associated not only with motor dysfunctions but also cognitive-affective symptoms. The main goal of the proposed work is to gain an understanding of the functional organization of the basal ganglia and its dopamine- containing input systems in the primate and to relate findings from experiments on normal and MPTP-treated primates to observations on postmortem human brains from normal individuals and from persons who suffered premortem extrapyramidal disorders such as Parkinson's disease, progressive supranuclear palsy and Huntington's disease. Experiments are proposed to study the distribution of neurotransmitter-related compounds in the striatum, pallidum and substantia nigra and to relate the chemoarchitecture of these regions to their input-output connections. Special emphasis is to be placed upon the cholinergic and dopaminergic mechanisms of the basal ganglia, on the neuropeptide-containing elements there, and on neuroleptic- related sigma receptor sites insofar as they are related to the dopamine-containing nuclei of the midbrain. Studies are planned to extend these observations by monitoring the effects of in vivo pharmacological manipulations. By coordinating observations in monkey and human, it is hoped that significant progress can be made toward an understanding of the basal ganglia in health and disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS025529-03
Application #
3410764
Study Section
Neurology A Study Section (NEUA)
Project Start
1988-07-01
Project End
1995-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
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
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
Amemori, Satoko; Amemori, Ken-Ichi; Cantor, Margaret L et al. (2015) A non-invasive head-holding device for chronic neural recordings in awake behaving monkeys. J Neurosci Methods 240:154-60
Graybiel, Ann M; Grafton, Scott T (2015) The striatum: where skills and habits meet. Cold Spring Harb Perspect Biol 7:a021691

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