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ORGANIZATION OF THE CORTICAL PROJECTION TO THE BASAL GANGLIA

Award Number: R01NS057722
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2008
PERIOD OF PERFORMANCE END DATE: 02/28/2013

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ORGANIZATION OF THE CORTICAL PROJECTION TO THE BASAL GANGLIA - DESCRIPTION (provided by applicant): Our previous work in rats suggests that cortical neurons projecting to brainstem premotor cell groups and spinal cord via the pyramidal tract (PT-type) preferentially target striatal neurons projecting to the external pallidal segment (GPe), while cortical neurons having only intratelencephalic projections (IT- type) preferentially target striatal neurons projecting to the internal pallidal segment (GPi) and/or the substantia nigra pars reticulata (SNr). These findings suggest that PT-type corticostriatal neurons may provide striato-GPe neurons with information about cortical motor commands needed for their role in suppressing potentially conflicting movements, while integration of IT-type input from diverse cortical areas may be required for striato-GPi/SNr neurons to play their role in initiating desired movement. Synaptic facilitation or disfacilitation of subsets of these inputs could play a role in motor learning. Our conclusions about differential cortical inputs to the two main types of striatal projection neurons are, however, based on preferential but not exclusive labeling of striatal neuron types. Moreover, we did not distinguish between striato-GPi and striato-SNr neurons in these prior studies. Thus, the extent to which each of the three main types of striatal projection neurons in rats receive input from more than one type of cortical neuron remains uncertain. Additionally, we also do now know if our findings for rats are true for primates, and thus clinically relevant to the human basal ganglia. In Aim 1 of the current proposal, we will use in vivo intracellular methods in rats to record from individual striatal projection neurons and then at the end of the physiology session identify their type by biocytin-filling the neuron (and later tracing the axon of each to its destination). For each neuron we will use electrophysiological and LM/EM anatomical methods, so as to characterize the extent of the specificity of the IT input for striato-GPi/SNr neurons and the PT input for striato-GPe neurons. In Aims 2 and 3, we will determine by dextran amine labeling, immunolabeling and EM analysis if IT-type terminals preferentially target striato-GPi and striato-SNr neurons while PT-type terminals preferentially target striato-GPe neurons in monkeys. Given the critical roles of the cortical input to striatum in providing an instructive signal to the striatum and in the plasticity underlying motor learning, our studies will: 1) help reveal how the striato-GPi/SNr and striato-GPe neurons play complementary roles in motor control; 2) help clarify the mechanisms underlying the role of the basal ganglia in movement initiation and in the execution of movement sequences; and 3) help explain the relationship between the role of the basal ganglia in motor learning and in motor performance. PUBLIC HEALTH RELEVANCE This study will clarify which neurons of cerebral cortex communicate with each of the two circuits of the basal ganglia, one of which facilitates desired movements and the other suppresses unwanted movements. The findings will clarify how the information provided by cerebral cortex enables the basal ganglia to play its role in movement control and in the learning of new motor routines. The findings will suggest new insights into the role of abnormalities in the cortical input to striatum in Huntington's disease, Parkinson's disease, Tourette Syndrome, and obsessive-compulsive disorder, and thereby suggest new therapeutic approaches for treating these disorders.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2012 ( Subtotal = $312,988 )
2012	2012	UNIVERSITY OF TENNESSEE CENTER FOR THE HEALTH SCIENCES	62 SOUTH DUNLAP STREET	MEMPHIS	TN	38103	SHELBY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	3/1/2012	NON-COMPETING CONTINUATION	$312,988
														Subtotal = $312,988

Issue Date FY: 2011 ( Subtotal = $312,988 )
2011	2011	UNIVERSITY OF TENNESSEE CENTER FOR THE HEALTH SCIENCES	62 SOUTH DUNLAP STREET	MEMPHIS	TN	38103	SHELBY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	2/24/2011	NON-COMPETING CONTINUATION	$287,438
2011	2011	UNIVERSITY OF TENNESSEE CENTER FOR THE HEALTH SCIENCES	62 SOUTH DUNLAP STREET	MEMPHIS	TN	38103	SHELBY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	6/8/2011	NON-COMPETING CONTINUATION	$25,550
														Subtotal = $312,988

Issue Date FY: 2010 ( Subtotal = $316,182 )
2010	2010	UNIVERSITY OF TENNESSEE CENTER FOR THE HEALTH SCIENCES	62 SOUTH DUNLAP STREET	MEMPHIS	TN	38103	SHELBY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	3/11/2010	NON-COMPETING CONTINUATION	$316,182
														Subtotal = $316,182

Issue Date FY: 2009 ( Subtotal = $319,375 )
2009	2009	UNIVERSITY OF TENNESSEE CENTER FOR THE HEALTH SCIENCES	62 SOUTH DUNLAP STREET	MEMPHIS	TN	38103	SHELBY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	4/7/2009	NON-COMPETING CONTINUATION	$31,937
2009	2009	UNIVERSITY OF TENNESSEE CENTER FOR THE HEALTH SCIENCES	62 SOUTH DUNLAP STREET	MEMPHIS	TN	38103	SHELBY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	2/23/2009	NON-COMPETING CONTINUATION	$287,438
														Subtotal = $319,375

Issue Date FY: 2008 ( Subtotal = $319,375 )
2008	2008	UNIVERSITY OF TENNESSEE	WEST CUMBERLAND AVENUE, SW	KNOXVILLE	TN	37916	KNOX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	1/29/2008	NEW	$319,375
														Subtotal = $319,375

Grand Total All Awards = $1,580,908

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ORGANIZATION OF THE CORTICAL PROJECTION TO THE BASAL GANGLIA

Award Number: R01NS057722

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/01/2008

PERIOD OF PERFORMANCE END DATE: 02/28/2013

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