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Abstract

Grant Number:	1Z01MH002497-14
Project Title:	Functional Organization Of The Basal Ganglia

PI Information:	Name	Email	Title
	GERFEN, CHARLES R.	gerfenc@mail.nih.gov	CHIEF, LAB OF SYSTEMS NEUROSCIENCE

Abstract: Resesarch in the Section on Neuroanatomy is concerned with the role of the basal ganglia in behavior. The basal ganglia receives inputs from all cortical areas, processes that input through the striatum, whose output pathways provide feedback, through the thalamus, to cortical areas involved in the selection and control of behavior. Our work takes two approaches. The first uses neuroanatomical methods to study the connectional organization of the basal ganglia. The second approach uses molecular biologic techniques to study the the regulation of gene expression responsible for neuronal plasticity within the striatum. Current work is focused on extending our prior findings that dopamine, through the segregation of the D1 and D2 dopamine receptor subtypes in the "direct" and "indirect" striatal output neurons, regulates the balanced function of striatal output pathways. Neuromodulators such as dopamine act to alter the long term response of neurons to synaptic input, such as the glutamatergic excitatory input from the cortex. Such neuroplasticity is mediated by the activation of neurotransmitter receptor-mediated activation of protein kinase signal transduction pathways, which result in the activation of transcription factors and induction of specific genes that are responsible for altering synaptic responses. We demonstrated that in the striatum, the "direct" and "indirect" striatal projection neurons support distinct forms of neuronal plasticity that affect responses to cortical input, through the differential activation of distinct protein kinase signaling pathways, and dopamine maintains these different forms of response. Dysfunction of the striatum following dopamine lesions in animal models of Parkinson's disease, appear to be due to a particularly aberrant form of neuronal plasticity that is due to a switch in the regulation of a particular protein kinase signal transduction pathway. The purpose of these studies is to better establish how disorders of the basal ganglia, such as Parkinson's disease, result in clinical movement disorders, and whether the basal ganglia might also be involved in such mental disorders, such as Attention Deficit Hyperactivity Disorder, or in the abuse of psychoactive drugs.

Public Health Relevance:
This Public Health Relevance is not available.

Thesaurus Terms:
basal ganglia, brain mapping, cerebral cortex, neuroanatomy, neurobiology
Parkinson's disease, brain /spinal pathway /tract, corpus striatum, dopamine, dopamine receptor, gene expression, neuropharmacology, neurotransmitter receptor, receptor expression, regulatory gene

Institution:
Fiscal Year:	2003
Department:
Project Start:
Project End:
ICD:	NATIONAL INSTITUTE OF MENTAL HEALTH
IRG:	LSN

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