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Interrogating Synaptic Mechanisms Underlying Contextual Fear Conditioning Amnesia in Rodent Model of Highly Repetitive Mild Traumatic Brain Injury

Award Number: F30NS122281
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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Abstract Traumatic brain injury is the most common neurological disorder and 80% consist of mild traumatic brain injury (mTBI). The severity and persistence of cognitive symptoms is increased with additional repeat mTBIs (rmTBI). A high frequency head impact (HF-HI) mouse model of rmTBI developed by the Burns lab displays decreased learning and changes in transcriptomic profiles related to synaptic signaling accompanied by decreased plasticity and synaptic changes in CA1 pyramidal neurons. This would suggest that synaptic modifications underly the anterograde cognitive symptoms following rmTBI. It is still unknown how rmTBI directly effects an already established memory. Engrams, defined as lasting physical or chemical changes in neurons, are the neural substrate underlying episodic memory. Studies in transgenic rodents use immediate early genes and pharmacological labeling, can tag engram cells in contextual fear conditioning (CFC) paradigms. Subsequent optogenetic reactivation of engrams in the hippocampal formation is sufficient to elicit memory recall outside the conditioned context and reanimate fear memories in models of amnesia. Preliminary data has shown that the HF-HI model reduces freezing time in CFC probe trials and engram cells expressing Chr2-YFP can be tagged in transgenic engram mice. I propose to interrogate immunohistological and electrophysiological properties of engram cells to explore architectural or synaptic modifications in the repeat head impact brain. I will also use optogenetics in vivo to reanimate amnestic memories. This research will explore how synaptic modification relates to retrograde cognitive deficits following rmTBI and probe memory recall, not memory substrate loss, as a mechanism for retrograde amnesia.


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 = $43,646 )
2024	2024	GEORGETOWN UNIVERSITY	MAIN CAMPUS	WASHINGTON	DC	20057	DISTRICT OF COLUMBIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	2/8/2024	NON-COMPETING CONTINUATION	$43,646
														Subtotal = $43,646

Issue Date FY: 2023 ( Subtotal = $52,694 )
2023	2023	GEORGETOWN UNIVERSITY	MAIN CAMPUS	WASHINGTON	DC	20057	DISTRICT OF COLUMBIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	1/5/2023	NON-COMPETING CONTINUATION	$34,052
2023	2023	GEORGETOWN UNIVERSITY	MAIN CAMPUS	WASHINGTON	DC	20057	DISTRICT OF COLUMBIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	2/13/2023	NON-COMPETING CONTINUATION	$942
2023	2023	GEORGETOWN UNIVERSITY	MAIN CAMPUS	WASHINGTON	DC	20057	DISTRICT OF COLUMBIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	2	4/21/2023	NON-COMPETING CONTINUATION	$17,700
														Subtotal = $52,694

Issue Date FY: 2022 ( Subtotal = $34,052 )
2022	2022	GEORGETOWN UNIVERSITY (THE)	37TH AND O ST NW	WASHINGTON	DC	20057	DISTRICT OF COLUMBIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	1/6/2022	NEW	$33,336
2022	2022	GEORGETOWN UNIVERSITY	MAIN CAMPUS	WASHINGTON	DC	20057	DISTRICT OF COLUMBIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	6/23/2022	NEW	$716
														Subtotal = $34,052

Grand Total All Awards = $130,392

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Interrogating Synaptic Mechanisms Underlying Contextual Fear Conditioning Amnesia in Rodent Model of Highly Repetitive Mild Traumatic Brain Injury

Award Number: F30NS122281

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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