The aim of the proposed research is to further our understanding of the way in which glutamatergic and dopaminergic synaptic transmission contribute to the function of the neostriatum. Previous experiments have demonstrated roles for both ionotropic and metabotropic glutamate receptors in corticostriatal synaptic transmission. In addition, two forms of synaptic depression (STD and LTD) have been observed at these synapses. Experiments are designed to determine: 1) The synaptic locus of alterations involved in striatal LTD; 2) The role of corticostriatal and nigrostriatal afferent inputs in eliciting striatal LTD; 3) The mechanisms involved in presynaptic modulation of transmission by metabotropic glutamate receptors. Glutamate or a related amino acid is the major excitatory neurotransmitter in the mammalian CNS. Within the caudate nucleus and putamen, glutamate- containing fibers from the cortex and possibly thalamus form synapses with neurons, most notably the medium spiny neurons. Activation of these synapses depolarizes striatal neurons which activates the neurons directly or increases the likelihood of their being activated by other inputs. A further understanding of the physiologic and pharmacologic properties of these synapses is critical to the appreciation of functional neostriatal circuitry. The dopaminergic nigrostriatal pathway also plays a prominent role in regulation of striatal function, and is critically involved in the neuropathology of Parkinson's disease and other neurological disorders involving the basal ganglia. However, relatively little is known about the consequences of activation of this pathway at the level of cellular physiology and synaptic transmission. It is our hypothesis that elucidation of the role of glutamatergic corticostriatal transmission and dopaminergic nigrostriatal transmission in striatal function will aid in the development of therapeutic approaches to disorders involving impairment of striatal function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS030470-05A1
Application #
2037515
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Program Officer
Baughman, Robert W
Project Start
1992-12-01
Project End
2001-02-28
Budget Start
1997-03-27
Budget End
1998-02-28
Support Year
5
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Physiology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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