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Development of Synaptic Inputs on Spinal Interneurons

Award Number: R01NS047357
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: 06/01/2004
PERIOD OF PERFORMANCE END DATE: 02/28/2026

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Development of Synaptic Inputs on Spinal Interneurons - PROJECT SUMMARY (30-lines) Movement depends on patterned spinal cord motor output necessary for coordinated muscle actions. This in turn, depends on spinal interneuron microcircuits that modulate motoneuron recruitment and firing. The recent explosion of genetically-defined interneurons has revolutionized the study of spinal motor circuits promising a more comprehensive and complete dissection of these important networks. The work started by devising genetic strategies to identify, label, study and modify activity of large groups of interneurons defined by their derivation from specific progenitor domains. This is the approach mostly taken in previous years. Much new information was obtained, but the biggest surprise was the large heterogeneity within each domain-lineage of spinal interneurons. It is thus now necessary to study the different subclasses of interneurons within each domain. This can only be accomplished with new animal models to target more restricted subgroups using intersectional genetics in which combinatorial expression of more than one gene is necessary for conditionally expressing fluorescent proteins or activity modulators to study them. This grant focuses on the V1 group. These are inhibitory interneurons with ipsilateral connections in the spinal cord and that have important roles shaping motoneuron activity. Over the years we and others have reported a variety of functions for V1 interneurons, including control of motoneuron firing by recurrent and reciprocal inhibition, being all Renshaw cells and some, but not all, Ia inhibitory interneurons (IaINs) derived from V1s. They also contribute to regulate flexion-extension alternation during movement and locomotion speed, providing respectively out-of-phase and in-phase inhibition during rhythmic locomotion. This functional diversity is parallel by the existence of many different genetically-defined subpopulations (by some estimates more than 50) organized into four major V1 clades. It is now important to analyze whether each subset is integrated in distinct microcircuits and responsible for specialized functions. We chose to focus in the next five years on the largest V1clade defined by the transcription factor Foxp2. Data gathered during the previous grant suggest this group is composed of at least three major subtypes and includes some cells with synaptology typical of IaINs. We have tested various intersectional strategies to study anatomically (using various viral approaches) the connectivity of Foxp2-V1s with different motor pools and primary afferents, and the postnatal development of these connections (Aim1). Then, we will analyze whether Foxp2-V1s are the only sources of V1-IaINs and how reciprocal inhibition is affected by genetically silencing them (Aim 2). Finally, we will reversibly silence these cells in the neonate and adult during locomotor stepping and use chronic EMG recordings and kinematics to analyze their role in muscle activation selection during rhythmic motor behaviors (Aim 3). The major goal is to uncover the functional organization of this major V1 group and their impact during postnatal maturation of motor function.


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: 2025 ( Subtotal = $413,817 )
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	18	3/11/2025	NON-COMPETING CONTINUATION	$413,817
														Subtotal = $413,817

Issue Date FY: 2024 ( Subtotal = $446,002 )
2024	2024	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	17	4/9/2024	NON-COMPETING CONTINUATION	$32,185
2024	2024	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	17	3/1/2024	NON-COMPETING CONTINUATION	$413,817
														Subtotal = $446,002

Issue Date FY: 2023 ( Subtotal = $459,796 )
2023	2023	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	16	3/22/2023	NON-COMPETING CONTINUATION	$459,796
														Subtotal = $459,796

Issue Date FY: 2022 ( Subtotal = $459,796 )
2022	2022	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	15	3/2/2022	NON-COMPETING CONTINUATION	$413,812
2022	2022	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	15	3/24/2022	NON-COMPETING CONTINUATION	$45,984
														Subtotal = $459,796

Issue Date FY: 2021 ( Subtotal = $459,312 )
2021	2021	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	14	5/5/2021	COMPETING CONTINUATION	$459,312
														Subtotal = $459,312

Issue Date FY: 2019 ( Subtotal = -$1 )
2019	2017	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	9/4/2019	NON-COMPETING CONTINUATION	-$1
														Subtotal = -$1

Issue Date FY: 2017 ( Subtotal = $341,250 )
2017	2017	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	13	6/6/2017	NON-COMPETING CONTINUATION	$34,125
2017	2017	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	5/1/2017	NON-COMPETING CONTINUATION	$307,125
														Subtotal = $341,250

Issue Date FY: 2016 ( Subtotal = $341,250 )
2016	2016	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	12	4/21/2016	NON-COMPETING CONTINUATION	$341,250
														Subtotal = $341,250

Issue Date FY: 2015 ( Subtotal = $341,250 )
2015	2015	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	3/26/2015	NON-COMPETING CONTINUATION	$341,250
														Subtotal = $341,250

Issue Date FY: 2014 ( Subtotal = $341,250 )
2014	2014	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	6/20/2014	COMPETING CONTINUATION	$341,250
														Subtotal = $341,250

Issue Date FY: 2013 ( Subtotal = $0 )
2013	2012	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	4/15/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2012 ( Subtotal = $332,281 )
2012	2012	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	2/1/2012	NON-COMPETING CONTINUATION	$332,281
														Subtotal = $332,281

Issue Date FY: 2011 ( Subtotal = $332,281 )
2011	2011	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	8	4/8/2011	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$305,156
2011	2011	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	8	6/27/2011	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$27,125
2011	2010	WRIGHT STATE UNIVERSITY	3640 COLONEL GLEN HWY	DAYTON	OH	45435	GREENE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	4/7/2011	NON-COMPETING CONTINUATION	$0
														Subtotal = $332,281

Issue Date FY: 2010 ( Subtotal = $310,768 )
2010	2010	WRIGHT STATE UNIVERSITY	3640 COLONEL GLEN HWY	DAYTON	OH	45435	GREENE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	1/19/2010	NON-COMPETING CONTINUATION	$310,768
														Subtotal = $310,768

Issue Date FY: 2009 ( Subtotal = $313,906 )
2009	2009	WRIGHT STATE UNIVERSITY	3640 COLONEL GLEN HWY	DAYTON	OH	45435	GREENE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	3/27/2009	NON-COMPETING CONTINUATION	$31,390
2009	2009	WRIGHT STATE UNIVERSITY	3640 COLONEL GLEN HWY	DAYTON	OH	45435	GREENE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	1/21/2009	NON-COMPETING CONTINUATION	$282,516
														Subtotal = $313,906

Issue Date FY: 2008 ( Subtotal = $313,906 )
2008	2008	WRIGHT STATE UNIVERSITY	3640 COLONEL GLEN HWY	DAYTON	OH	45435	GREENE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	2/1/2008	COMPETING CONTINUATION	$313,906
														Subtotal = $313,906

Issue Date FY: 2007 ( Subtotal = $283,183 )
2007	2007	WRIGHT STATE UNIVERSITY	3640 COLONEL GLEN HWY	DAYTON	OH	45435	GREENE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	2/14/2007	NON-COMPETING CONTINUATION	$283,183
														Subtotal = $283,183

Issue Date FY: 2006 ( Subtotal = $291,641 )
2006	2006	WRIGHT STATE UNIVERSITY	3640 COLONEL GLEN HWY	DAYTON	OH	45435	GREENE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	3/6/2006	NON-COMPETING CONTINUATION	$291,641
														Subtotal = $291,641

Issue Date FY: 2005 ( Subtotal = $323,659 )
2005	2005	WRIGHT STATE UNIVERSITY	3640 COLONEL GLEN HWY	DAYTON	OH	45435	GREENE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	3/10/2005	SUPPLEMENT FOR EXPANSION	$25,000
2005	2005	WRIGHT STATE UNIVERSITY	3640 COLONEL GLEN HWY	DAYTON	OH	45435	GREENE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	3/10/2005	NON-COMPETING CONTINUATION	$298,659
														Subtotal = $323,659

Issue Date FY: 2004 ( Subtotal = $298,659 )
2004	2004	WRIGHT STATE UNIVERSITY	3640 COLONEL GLEN HWY	DAYTON	OH	45435	GREENE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/31/2004	NEW	$298,659
														Subtotal = $298,659

Grand Total All Awards = $6,404,006

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Development of Synaptic Inputs on Spinal Interneurons

Award Number: R01NS047357

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: 06/01/2004

PERIOD OF PERFORMANCE END DATE: 02/28/2026

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