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Newborn Neurons in the Adult Hippocampal Network

Award Number: R01NS064025
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: 02/01/2009
PERIOD OF PERFORMANCE END DATE: 02/28/2025

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Newborn Neurons in the Adult Hippocampal Network - The dentate gyrus contributes to hippocampal memory encoding by transforming dense cortical patterns of sensory and spatial information into sparse neural representations of specific contexts. There is now overwhelming evidence that continual adult neurogenesis in the dentate gyrus in important for the ability to discriminate spatial contexts, but it is not clear how newly generated neurons contribute to dentate circuit function. Most theories have focused on the fact that newly-generated immature neurons have distinct physiological properties that potentially endow them with unique processing capabilities compared to larger population of mature neurons. Alternatively, an emerging idea is that adult-born neurons promote wide-spread plasticity of the pre-existing cortical-dentate circuit by modifying the function of existing neurons in a manner that promotes sparse activity. This could occur either by indirect circuit actions like feedback inhibition, as well as via direct interactions with existing excitatory synaptic connectivity. We recently showed that selectively increasing the number of adult-born neurons in mouse dentate gyrus reduces the excitatory synaptic connectivity of mature neurons, resulting in both functional and anatomical changes in entorhinal-dentate circuitry. These results and existing literature support a model wherein a static pool of cortical pre-synaptic terminals is dynamically distributed between newly integrating adult-born neurons and developmentally- generated mature neurons. The goal of this project is to test the overarching hypothesis that synaptic integration of adult-born neurons has disproportionate effects on circuit function via redistribution of cortical synaptic connectivity. First, we will map and quantify the presynaptic changes that accompany neurogenesis-induced loss of cortical synapses with mature neurons. Second, we will test the prediction that availability of cortical presynaptic terminals is a limiting factor in the integration of newborn GCs that potentially contributes to the reduced rate new neuron maturation across adulthood. Finally, we will test potential consequences of synaptic redistribution on the sparsity of neural activity and synaptic plasticity, and the requirement for synaptic redistribution for neurogenesis-sensitive behaviors. We will use a combination of viral manipulations, electrophysiology, imaging and behavioral analysis to test the prediction that synaptic re- distribution limits the integration of adult-born neurons during adulthood and sparsifies neural activity, as well as contributes to behaviors that are sensitive to neurogenesis. Together our results will generate fundamental new knowledge about the role of neurogenesis in cortical-dentate circuitry, and potentially provide insight into how this circuit changes across adulthood as neurogenesis declines. Understanding how neurogenesis contributes to hippocampal function is important for devising strategies to counteract the consequences of disrupted neurogenesis that occurs during aging and many neurological conditions.


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 = -$74,347 )
2025	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	14	5/7/2025	NON-COMPETING CONTINUATION	-$74,347
														Subtotal = -$74,347

Issue Date FY: 2023 ( Subtotal = $404,380 )
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	14	3/30/2023	NON-COMPETING CONTINUATION	$404,380
														Subtotal = $404,380

Issue Date FY: 2022 ( Subtotal = $404,380 )
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	13	6/22/2022	NON-COMPETING CONTINUATION	$40,441
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	2/25/2022	NON-COMPETING CONTINUATION	$363,939
														Subtotal = $404,380

Issue Date FY: 2021 ( Subtotal = $404,380 )
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	12	3/8/2021	NON-COMPETING CONTINUATION	$404,380
														Subtotal = $404,380

Issue Date FY: 2020 ( Subtotal = $502,859 )
2020	2020	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	2/24/2020	NON-COMPETING CONTINUATION	$502,859
														Subtotal = $502,859

Issue Date FY: 2019 ( Subtotal = $514,272 )
2019	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	3/1/2019	COMPETING CONTINUATION	$514,272
2019	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	10	6/19/2019	COMPETING CONTINUATION	$73,736
2019	2018	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	9	6/19/2019	NON-COMPETING CONTINUATION	-$73,736
														Subtotal = $514,272

Issue Date FY: 2018 ( Subtotal = $380,313 )
2018	2018	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	9	4/25/2018	NON-COMPETING CONTINUATION	$38,032
2018	2018	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	2/23/2018	NON-COMPETING CONTINUATION	$342,281
														Subtotal = $380,313

Issue Date FY: 2017 ( Subtotal = $380,313 )
2017	2017	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	2/16/2017	NON-COMPETING CONTINUATION	$342,282
2017	2017	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	8	6/7/2017	NON-COMPETING CONTINUATION	$38,031
														Subtotal = $380,313

Issue Date FY: 2016 ( Subtotal = $380,313 )
2016	2016	UNIVERSITY OF ALABAMA AT BIRMINGHAM	1530 3rd Avenue South, AB 1170	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	2/24/2016	NON-COMPETING CONTINUATION	$380,313
														Subtotal = $380,313

Issue Date FY: 2015 ( Subtotal = $380,313 )
2015	2015	UNIVERSITY OF ALABAMA AT BIRMINGHAM	1530 3rd Avenue South, AB 1170	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	1/20/2015	COMPETING CONTINUATION	$380,313
														Subtotal = $380,313

Issue Date FY: 2014 ( Subtotal = $0 )
2014	2013	UNIVERSITY OF ALABAMA AT BIRMINGHAM	1530 3rd Avenue South, AB 1170	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	2/27/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2013 ( Subtotal = $299,964 )
2013	2013	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	5/27/2013	NON-COMPETING CONTINUATION	$20,204
2013	2013	UNIVERSITY OF ALABAMA AT BIRMINGHAM	1530 3rd Avenue South, AB 1170	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	5	2/27/2014	NON-COMPETING CONTINUATION	$0
2013	2013	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	1/17/2013	NON-COMPETING CONTINUATION	$279,760
														Subtotal = $299,964

Issue Date FY: 2012 ( Subtotal = $310,844 )
2012	2012	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	1/30/2012	NON-COMPETING CONTINUATION	$310,844
														Subtotal = $310,844

Issue Date FY: 2011 ( Subtotal = $310,844 )
2011	2011	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	6/3/2011	NON-COMPETING CONTINUATION	$25,375
2011	2011	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	1/14/2011	NON-COMPETING CONTINUATION	$285,469
2011	2009	UNIVERSITY OF ALABAMA AT BIRMINGHAM	1530 3rd Avenue South, AB 1170	BIRMINGHAM	AL	35294	JEFFERSON	USA	Trans-NIH Recovery Act Research Support	001	1	5/23/2011	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $310,844

Issue Date FY: 2010 ( Subtotal = $314,016 )
2010	2010	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	1/14/2010	NON-COMPETING CONTINUATION	$314,016
														Subtotal = $314,016

Issue Date FY: 2009 ( Subtotal = $601,208 )
2009	2009	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	1/28/2009	NEW	$317,188
2009	2009	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Trans-NIH Recovery Act Research Support	002	1	8/13/2009	SUPPLEMENT FOR EXPANSION	$256,499
2009	2009	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Trans-NIH Recovery Act Research Support	001	1	7/20/2009	SUPPLEMENT FOR EXPANSION	$27,521
														Subtotal = $601,208

Grand Total All Awards = $5,514,052

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Newborn Neurons in the Adult Hippocampal Network

Award Number: R01NS064025

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: 02/01/2009

PERIOD OF PERFORMANCE END DATE: 02/28/2025

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