Tuesday, November 4, 2025 11/4/2025

Mossy Cells in Temporal Lobe Epilepsy

Award Number: R37NS126529
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: 01/01/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2025

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Mossy Cells in Temporal Lobe Epilepsy - PROJECT ABSTRACT Temporal lobe epilepsy (TLE) is a disorder with recurrent, debilitating seizures as well as comorbidities. A focus of research has been the dentate gyrus (DG), which is composed primarily of glutamatergic granule cells (GCs) that provide the output of the DG to hippocampal area CA3. One reason for the attention to the DG is that the GCs can inhibit seizures and also initiate them. GCs also contribute to the hallmark TLE neuropathology called mesial temporal sclerosis (MTS) which contributes to epileptogenesis. Mossy cells (MCs) are another glutamatergic DG cell and innervate GCs, so they are in a position to regulate GCs and seizures. MCs also innervate DG GABAergic neurons, and this action is considered to be strong normally, and leads to inhibition of GCs. We propose a different view, that both the excitatory and inhibitory actions of MCs on GCs have important roles and these roles are especially important in TLE. Our central hypothesis is that MC excitation of GCs strengthens during the initial insult that leads to TLE and this effect promotes epileptogenesis. In contrast, in chronic epilepsy, we hypothesize a very different MC role. We suggest that MCs resume their normal role to primarily activate GABAergic neurons which reduce chronic seizures. Therefore, during the initial insult, MCs should be inhibited for the best outcomes and during chronic epilepsy MCs should be activated. If supported, this hypothesis would be a paradigm shift. In addition, the proposed experiments will fill major gaps in knowledge about MCs and epilepsy. To address the hypothesis, we will use optogenetics and chemogenetics in mouse models of TLE with selective expression of Cre recombinase in MCs. Seizures will be examined as well as comorbidities. Together these experiments will test novel hypotheses and fill several knowledge gaps about epilepsy. Furthermore, the experiments will potentially give rise to new approaches for therapeutics.


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 = $550,861 )
2025	2025	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	140 OLD ORANGEBURG RD BLDG 35	ORANGEBURG	NY	10962	ROCKLAND	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	12/16/2024	NON-COMPETING CONTINUATION	$417,080
2025	2025	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	140 OLD ORANGEBURG RD BLDG 35	ORANGEBURG	NY	10962	ROCKLAND	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	7/25/2025	NON-COMPETING CONTINUATION	$46,342
2025	2025	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	140 OLD ORANGEBURG RD BLDG 35	ORANGEBURG	NY	10962	ROCKLAND	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	8/28/2025	SUPPLEMENT FOR EXPANSION	$87,439
														Subtotal = $550,861

Issue Date FY: 2024 ( Subtotal = $447,137 )
2024	2024	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	140 OLD ORANGEBURG RD BLDG 35	ORANGEBURG	NY	10962	ROCKLAND	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	4/9/2024	NON-COMPETING CONTINUATION	$32,270
2024	2024	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	140 OLD ORANGEBURG RD BLDG 35	ORANGEBURG	NY	10962	ROCKLAND	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	12/28/2023	NON-COMPETING CONTINUATION	$414,867
														Subtotal = $447,137

Issue Date FY: 2023 ( Subtotal = $460,964 )
2023	2023	RESEARCH FOUNDATION FOR MENTAL HYGIENE INC	140 OLD ORANGEBURG RD	ORANGEBURG	NY	10962	ROCKLAND	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	12/15/2022	NEW	$460,964
														Subtotal = $460,964

Grand Total All Awards = $1,458,962

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Mossy Cells in Temporal Lobe Epilepsy

Award Number: R37NS126529

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: 01/01/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2025

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