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SYNAPTIC CHANGE IN CINGULATE CORTEX AFTER AMPUTATION

Award Number: R01NS042722
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: HEALTH SERVICES
PERIOD OF PERFORMANCE START DATE: 09/30/2003
PERIOD OF PERFORMANCE END DATE: 06/30/2007

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SYNAPTIC CHANGE IN CINGULATE CORTEX AFTER AMPUTATION - DESCRIPTION (provided by applicant): The long-term goal of this project is to characterize excitatory synaptic transmission and plasticity in the anterior cingulate cortex (ACC) and explore their roles in cortical sensory responses after amputation. Understanding of these mechanisms may provide insights into pathophysiological changes in amputees, such as phantom limb sensation and phantom pain. Patients who have suffered amputation in a variety of clinical contexts, including trauma and cancer, often experience abnormal sensory experiences, including phantom limb sensation and phantom pain. It can happen at 24 hours after surgery and persists for months or years. Effective clinical prevention and treatment are not available, due to poor understanding of the mechanisms. Recent human studies demonstrate that cortical reorganization in forebrain areas, including the ACC, correlates with phantom pain in amputees. Little is known about synaptic mechanisms and possible changes in the ACC after amputation. Here, we plan to use both in vitro brain slices and in vivo animals to investigate long-lasting changes in the ACC after amputation. Four Specific Aims are proposed: To characterize synaptic transmission and plasticity in the ACC, electrophysiological recordings will be performed from ACC slices and the contribution of different glutamate receptors and L-type voltage-gated calcium channels to synaptic transmission and plasticity will be studied. To examine sensory responses in the ACC of anesthetized mice, intracellular recordings will be performed from ACC cells in anesthetized mice. Sensory responses to peripheral electrical shocks will be recorded and the cells will be labeled by intracellular injection of the dye biocytin. To study the physiological modulation of ACC after amputation, sensory responses to peripheral electrical shocks will be performed to detect long-lasting changes lasting hours after amputation. Late changes (weeks to months) after amputation will be also investigated. Finally, to explore the molecular mechanism contributing to amputation induced plastic changes; the contribution of calcium-dependent signaling molecules to amputation-induced plastic changes in the ACC will be studied. The proposed studies will characterize basic synaptic mechanisms in the ACC and determine the synaptic and molecular mechanisms for amputation related synaptic plasticity in the ACC. This information will provide a potential neuronal basis for understanding phantom limb sensation and phantom pain.


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: 2006 ( Subtotal = $225,425 )
2006	2006	UNIVERSITY OF TORONTO	**	TORONTO, ONTARIO		00000		CAN	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	8/6/2006	NON-COMPETING CONTINUATION	$225,425
														Subtotal = $225,425

Issue Date FY: 2005 ( Subtotal = $230,850 )
2005	2005	UNIVERSITY OF TORONTO	**	TORONTO, ONTARIO		00000		CAN	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	7/8/2005	NON-COMPETING CONTINUATION	$230,850
														Subtotal = $230,850

Issue Date FY: 2004 ( Subtotal = $230,850 )
2004	2004	UNIVERSITY OF TORONTO	**	TORONTO, ONTARIO		00000		CAN	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	6/30/2004	NON-COMPETING CONTINUATION	$230,850
														Subtotal = $230,850

Issue Date FY: 2003 ( Subtotal = $230,850 )
2003	2003	UNIVERSITY OF TORONTO	**	TORONTO, ONTARIO		00000		CAN	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/30/2003	NEW	$230,850
														Subtotal = $230,850

Grand Total All Awards = $917,975

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SYNAPTIC CHANGE IN CINGULATE CORTEX AFTER AMPUTATION

Award Number: R01NS042722

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: HEALTH SERVICES

PERIOD OF PERFORMANCE START DATE: 09/30/2003

PERIOD OF PERFORMANCE END DATE: 06/30/2007

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