Monday, June 30, 2025 6/30/2025

Role of TLR4 in Neuronal Excitability and Memory Function

Award Number: F31NS120620
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/01/2021
PERIOD OF PERFORMANCE END DATE: 03/22/2024

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Role of TLR4 in Neuronal Excitability and Memory Function - Project Summary/Abstract Toll-Like Receptor 4 (TLR4) is an innate immune receptor that is enhanced after brain injury and is implicated in modulating excitability in the hippocampal dentate gyrus. We find that suppressing TLR4 after brain injury reduces seizure susceptibility and memory deficits however has opposite effects in controls. In pilot studies, TLR4 signaling increases synaptic inhibition to dentate granule cells in controls while reducing it after TBI, indicating that inhibition may be central to the differential TLR4 effects in control and injured brain. TLR4 is localized in dentate hilar neurons and co-localizes with somatostatin, not parvalbumin interneurons. Since TLR4 effects on inhibition correlate with dentate excitability and memory outcomes, I propose that cell type specific and injury-state dependent TLR4 modulation of GABAergic synapses regulate dentate excitability and memory processing. Using single/dual patch clamp recordings, cell-specific patterned optogenetic neuronal activation and pharmacology in a rodent model of brain injury, I will resolve TLR4 regulation of synaptic inputs from SOM+ and PV+ neurons to granule cells in control and injured animals. Mice with cell-specific deletion of TLR4 will be subject to brain injury and probed for TLR4 regulation of network function using a novel in-vitro temporal pattern separation assay and behavioral pattern separation tasks. The study will advance basic knowledge on immune regulation of excitability and memory processing and identify potential targets to limit post-traumatic changes in neuronal activity.


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 = -$5,649 )
2025	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	1/23/2025	NON-COMPETING CONTINUATION	-$5,649
														Subtotal = -$5,649

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	6/3/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $25,061 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	9/21/2023	NON-COMPETING CONTINUATION	$0
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	8/17/2023	NON-COMPETING CONTINUATION	$25,061
														Subtotal = $25,061

Issue Date FY: 2022 ( Subtotal = $46,752 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	900 UNIVERSITY AVE	RIVERSIDE	CA	92521	RIVERSIDE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	8/9/2022	NON-COMPETING CONTINUATION	$46,752
														Subtotal = $46,752

Issue Date FY: 2021 ( Subtotal = $46,036 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	7/8/2021	NEW	$0
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	7/8/2021	NEW	$46,036
														Subtotal = $46,036

Grand Total All Awards = $112,200

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Role of TLR4 in Neuronal Excitability and Memory Function

Award Number: F31NS120620

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/01/2021

PERIOD OF PERFORMANCE END DATE: 03/22/2024

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