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Generation and Description of Neuronal Morphology and Connectivity

Award Number: R01NS039600
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: 08/01/1999
PERIOD OF PERFORMANCE END DATE: 04/30/2025

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Generation and Description of Neuronal Morphology and Connectivity - Dendritic and axonal morphologies play fundamental roles in physiological brain function and pathological dysfunction by affecting synaptic integration, spike train transmission, and circuit connectivity. Incorporating published experimental data into accurate, full-scale, and biologically plausible neural network simulations is important for quantitatively bridging the sub-cellular and systems-levels. We successfully designed, implemented, and freely distributed to the community computer software and databases to reconstruct, analyze, visualize, simulate, and share the 3D tree-like shape of neurons collected from any labeling and visualization techniques, animal species, brain regions, developmental stages, and experimental conditions. We imaged by light microscopy, digitally traced, and shared new data, and we provided our peers with the electronic means of freely doing the same. Moreover, we combined those data with computational models of membrane biophysics to investigate the neuronal structure-activity relationship with a special focus on the hippocampus and entorhinal cortex due to their central role in spatial representation and episodic memory. We additionally annotated a massive amount of cellular properties in an open-source web-based portal of neuron types in the rodent hippocampal formation. We now propose to expand this research approach with three specific aims. The first is to augment the power, scope, and usability of the NeuroMorpho.Org repository of digital tracings. We plan to more than double the number of shared reconstructions while enhancing the human- and machine-accessible utility by adding ‘search similar’ and summary reporting functionalities. Most importantly for long-term sustainability, we will dramatically modernize the information technology infrastructure of this resource to enable unsolicited submissions directly from authors, continuous agile releases, and community crowdsourcing. The second aim is to complete the Hippocampome.org knowledge base by adding synaptic information, including connection probabilities, physiology, and plasticity, and linking them to the existing morphological, physiological, and molecular properties of pre- and post-synaptic neurons. This will enable the implementation of a real-scale spiking neural network model to run predictive simulations of activity dynamics and computational functions. The third aim is to develop an innovative approach to classify neurons directly from network connectivity, validating it with the hippocampal circuit and deploying it on open-access high-throughput data from a popular model organism. Together, these three aims will allow us (and others) to test hypotheses relating neuronal morphology to molecular and developmental determinants on the one hand, and to functional circuits on the other. The focus of this application on structural plasticity is especially relevant to disabling neurological diseases prominently involving the hippocampal formation, including epilepsy and Alzheimer’s. Our proposed data-driven, biologically realistic network simulations may shed light on the role of specific neuron types and of their interactions in impairments of memory formation and retrieval.


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: 2024 ( Subtotal = $357,882 )
2024	2024	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DR	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	24	3/27/2024	NON-COMPETING CONTINUATION	$332,055
2024	2024	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DR	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	24	4/9/2024	NON-COMPETING CONTINUATION	$25,827
														Subtotal = $357,882

Issue Date FY: 2023 ( Subtotal = $368,950 )
2023	2023	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DR	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	23	5/11/2023	NON-COMPETING CONTINUATION	$368,950
														Subtotal = $368,950

Issue Date FY: 2022 ( Subtotal = $368,950 )
2022	2022	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DR	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	22	4/25/2022	NON-COMPETING CONTINUATION	$368,950
														Subtotal = $368,950

Issue Date FY: 2021 ( Subtotal = $368,950 )
2021	2021	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DR	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	21	4/20/2021	NON-COMPETING CONTINUATION	$368,950
2021	2018	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DR	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	19	5/23/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $368,950

Issue Date FY: 2020 ( Subtotal = $368,950 )
2020	2020	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DR	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	20	3/30/2020	COMPETING CONTINUATION	$368,950
														Subtotal = $368,950

Issue Date FY: 2018 ( Subtotal = $325,063 )
2018	2018	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DR	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	19	4/30/2018	NON-COMPETING CONTINUATION	$325,063
														Subtotal = $325,063

Issue Date FY: 2017 ( Subtotal = $361,874 )
2017	2017	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DR	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	18	4/25/2017	NON-COMPETING CONTINUATION	$292,556
2017	2017	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DR	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	18	5/31/2017	NON-COMPETING CONTINUATION	$32,507
2017	2017	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DR	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	18	7/17/2017	SUPPLEMENT FOR EXPANSION	$36,811
														Subtotal = $361,874

Issue Date FY: 2016 ( Subtotal = $325,063 )
2016	2016	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DRIVE	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	17	5/3/2016	NON-COMPETING CONTINUATION	$325,063
														Subtotal = $325,063

Issue Date FY: 2015 ( Subtotal = $325,063 )
2015	2015	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DRIVE	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	16	4/23/2015	NON-COMPETING CONTINUATION	$325,063
														Subtotal = $325,063

Issue Date FY: 2014 ( Subtotal = $325,063 )
2014	2014	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DRIVE	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	15	12/31/2013	COMPETING CONTINUATION	$325,063
														Subtotal = $325,063

Issue Date FY: 2013 ( Subtotal = $287,871 )
2013	2014	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DRIVE	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	005	15	9/24/2013	COMPETING CONTINUATION	-$325,063
2013	2014	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DRIVE	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	15	9/21/2013	COMPETING CONTINUATION	$325,063
2013	2013	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DRIVE	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	14	9/24/2013	NON-COMPETING CONTINUATION	$0
2013	2013	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DRIVE	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	14	5/24/2013	NON-COMPETING CONTINUATION	$19,390
2013	2013	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DRIVE	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	14	4/17/2013	NON-COMPETING CONTINUATION	$268,481
2013	2013	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DRIVE	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	14	9/20/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $287,871

Issue Date FY: 2012 ( Subtotal = $334,092 )
2012	2012	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DRIVE	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	5/1/2012	NON-COMPETING CONTINUATION	$297,279
2012	2012	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DRIVE	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	13	8/10/2012	SUPPLEMENT FOR EXPANSION	$36,813
														Subtotal = $334,092

Issue Date FY: 2011 ( Subtotal = $292,262 )
2011	2011	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DRIVE	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	12	6/2/2011	NON-COMPETING CONTINUATION	$23,858
2011	2011	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DRIVE	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	12	4/7/2011	NON-COMPETING CONTINUATION	$268,404
														Subtotal = $292,262

Issue Date FY: 2010 ( Subtotal = $300,538 )
2010	2010	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DRIVE	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	4/22/2010	NON-COMPETING CONTINUATION	$300,538
														Subtotal = $300,538

Issue Date FY: 2009 ( Subtotal = $299,637 )
2009	2009	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DRIVE	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	10	4/30/2009	COMPETING CONTINUATION	$299,637
2009	2007	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DRIVE	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	3/17/2009	NON-COMPETING CONTINUATION	$0
2009	2007	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DRIVE	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	9	4/30/2009	NON-COMPETING CONTINUATION	$0
														Subtotal = $299,637

Issue Date FY: 2007 ( Subtotal = $312,148 )
2007	2007	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DRIVE	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	7/17/2007	NON-COMPETING CONTINUATION	$312,148
														Subtotal = $312,148

Issue Date FY: 2006 ( Subtotal = $319,978 )
2006	2006	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DRIVE	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	5/16/2006	NON-COMPETING CONTINUATION	$319,978
														Subtotal = $319,978

Issue Date FY: 2005 ( Subtotal = $326,475 )
2005	2005	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DRIVE	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	7/29/2005	NON-COMPETING CONTINUATION	$326,475
														Subtotal = $326,475

Issue Date FY: 2004 ( Subtotal = $326,475 ) (Continued on the next page)
Grand Total All Awards = $7,040,208

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Generation and Description of Neuronal Morphology and Connectivity

Award Number: R01NS039600

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: 08/01/1999

PERIOD OF PERFORMANCE END DATE: 04/30/2025

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