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INJURY-INDUCED SPATIAL MEMORY IMPAIRMENTS ARE LINKED TO UNCOORDINATED HIPPOCAMPAL NEURONAL FIRING

Award Number: R01NS120099
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: 01/15/2022
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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INJURY-INDUCED SPATIAL MEMORY IMPAIRMENTS ARE LINKED TO UNCOORDINATED HIPPOCAMPAL NEURONAL FIRING - PROJECT SUMMARY Traumatic brain injury (TBI) is the primary cause of death and disability in children and young adults1. TBI afflicts more than two million people annually in the United States, with an estimated 5.3 million TBI survivors living with lasting neurological impairments2,3. Mild TBI (mTBI) or concussion, accounts for nearly 90% of TBIs, with symptoms including deficits in learning and memory that profoundly affect the daily life and overall health of TBI survivors. Although TBI survivors suffer a range of cognitive impairments, deficits in learning and memory are most common4–6. The hippocampus is critically involved in both of these phenomena and highly susceptible to damage by TBI. Little is known about the precise mechanisms by which hippocampal damage produces memory deficits. Our preliminary data indicate that spatial memory (a type of episodic memory required for the discrimination of a spatially moved object), requires coordinated hippocampal theta and gamma rhythms in the local field potential and neuronal firing time-locked to those rhythms (Figures 7-9 and Innovation section below). Both of these required components are critically dependent on the activity of inhibitory neurons, and specific inhibitory neurons in hippocampal area CA1 and the dentate gyrus (DG) are significantly altered after TBI7,8. Based on these results we hypothesize that altered synaptic transmission in specific hippocampal inhibitory neuron populations alters the balance between excitation and inhibition (E/I balance), leading to local circuit dysfunction and significant weakening of the coordinated hippocampal oscillations and neuronal firing required for normal spatial memory. To test this hypothesis, in vivo and in vitro recordings together with chemogenetic manipulation of specific subpopulations of inhibitory neurons in area CA1 and DG will be used to determine whether restoring normal inhibitory neuron function will reinstate normal rhythms, time-locked action potential firing, and normal spatial memory.


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 = $396,000 )
2025	2025	THE CHILDREN'S HOSPITAL OF PHILADELPHIA	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	11/29/2024	NON-COMPETING CONTINUATION	$396,000
														Subtotal = $396,000

Issue Date FY: 2024 ( Subtotal = $426,800 )
2024	2024	THE CHILDREN'S HOSPITAL OF PHILADELPHIA	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	4/24/2024	NON-COMPETING CONTINUATION	$30,800
2024	2024	THE CHILDREN'S HOSPITAL OF PHILADELPHIA	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	1/16/2024	NON-COMPETING CONTINUATION	$396,000
														Subtotal = $426,800

Issue Date FY: 2023 ( Subtotal = $432,400 )
2023	2023	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	12/2/2022	NON-COMPETING CONTINUATION	$389,160
2023	2023	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	1/31/2023	NON-COMPETING CONTINUATION	$43,240
														Subtotal = $432,400

Issue Date FY: 2022 ( Subtotal = $427,080 )
2022	2022	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	1/6/2022	NEW	$427,080
														Subtotal = $427,080

Grand Total All Awards = $1,682,280

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INJURY-INDUCED SPATIAL MEMORY IMPAIRMENTS ARE LINKED TO UNCOORDINATED HIPPOCAMPAL NEURONAL FIRING

Award Number: R01NS120099

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: 01/15/2022

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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