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Disruption in the network communication of safety in epilepsy with comorbid anxiety

Award Number: R01NS105628
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: 04/15/2019
PERIOD OF PERFORMANCE END DATE: 02/28/2023

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Disruption in the network communication of safety in epilepsy with comorbid anxiety - Project Summary Epilepsy is highly comorbid with anxiety (Gaitatzis, 2005), which negatively impacts the quality of life of these patients (Johnson, 2004). To-date, we have little knowledge of the mechanisms underlying this comorbidity. Recent studies provide strong evidence for a role of network communciation between the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) in mediating the expression of fear and anxiety (Stujenske et al., 2014;Felix-Ortiz et al., 2016) (for review see (Tovote et al., 2015)). A recent collaborative effort between the Maguire and Reijmers' labs demonstrates a role for parvalbumin (PV) interneurons in mediating the transition between the network communication of fear and the behavioral expression of fear (Davis, 2017). Specifically, we demonstrate that silencing PV interneurons in the BLA increase the reactivation of fear neurons following extinction and are required to suppress the network communication of fear, findings which are correlated with an increase in the behavioral expression of fear. These studies have largely focused on transitions between states of safety and states of fear and anxiety under physiological conditions. Few studies have investigated how this neural circuit communication may become dysregulation or corrupted under pathological conditions. Here we propose to investigate whether dysregulation in the network communication of anxiety may play a role in comorbid anxiety in epilepsy. Our preliminary data demonstrates a loss of PV interneurons in the BLA of chronically epileptic mice which we hypothesize facilitates the reactivation of anxiety neurons, promoting the network communication and the behavior expression of anxiety.


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 = $0 )
2024	2022	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	12/15/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $392,933 )
2022	2022	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	2/10/2022	NON-COMPETING CONTINUATION	$353,637
2022	2022	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	3/23/2022	NON-COMPETING CONTINUATION	$39,296
														Subtotal = $392,933

Issue Date FY: 2021 ( Subtotal = $392,933 )
2021	2021	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	2/26/2021	NON-COMPETING CONTINUATION	$392,933
														Subtotal = $392,933

Issue Date FY: 2020 ( Subtotal = $392,933 )
2020	2020	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	3/19/2020	NON-COMPETING CONTINUATION	$392,933
														Subtotal = $392,933

Issue Date FY: 2019 ( Subtotal = $392,933 )
2019	2019	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	5/8/2019	NEW	$0
2019	2019	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	4/5/2019	NEW	$392,933
														Subtotal = $392,933

Grand Total All Awards = $1,571,732

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Disruption in the network communication of safety in epilepsy with comorbid anxiety

Award Number: R01NS105628

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: 04/15/2019

PERIOD OF PERFORMANCE END DATE: 02/28/2023

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