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Neural circuits regulating flight and panic behavior.

Award Number: R01MH122561
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2020
PERIOD OF PERFORMANCE END DATE: 12/31/2024

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Neural circuits regulating flight and panic behavior. - PROJECT SUMMARY Emotional behaviors, such as defensive responses to threat, are often dysregulated in mental illness. Currently, there is a poor understanding of the neural mechanisms that control transitions between modes and magnitudes of defensive responding. Obtaining such knowledge will provide significant progress toward the long-term goal of providing foundational knowledge used for the development of better therapeutics for mental illness. The overall objective of this application is to identify how distributed neuronal circuits control transitions to active forms of defensive behav- ior. The central hypothesis is that a widespread brain network that includes the central amygdala (CEA), ventromedial hypothalamus (VMH), periaqueductal grey (PAG), insular cortex (IC), and ventral hippocampus (vHIPP) controls defensive response transitions. The rationale that under- lies this proposal is that an enhanced understanding of these complex behavioral states and cir- cuits will provide foundational data for understanding multiple psychiatric disorders and their comorbidity. The proposed research tests the central hypothesis with three specific aims: 1) Iden- tify the functional role of specific projection pathways in defensive action selection; 2) Determine the impact of structures afferent to the CEA on flight behavior; and 3) Define the neuronal activity patterns that encode shifts in defensive states from freezing to flight to panic. The first aim will use viral vector delivery strategies and optogenetics to target and manipulate specific output path- ways of the CEA. The second aim will use retrograde targeting strategies to manipulate afferents to the CEA. Finally, the third aim will use deep-brain calcium imaging to monitor neural activity patterns in specific populations of projection neurons while mice transition through escalating lev- els of defensive responding. Successful completion of the proposed research will define mecha- nisms by which widespread brain networks mediate switching to active modes of defensive be- havior. The proposed research is innovative because it substantially departs from the status quo by investigating how the brain coordinates transitions between defensive behaviors. This will be significant because it will lay a foundation that facilitates understanding of the neuronal circuit basis of the maladaptive responses associated with mental illness. Indeed, this novel systems neuroscience approach to understanding how fear states are encoded will open new avenues of research into the neurobiological underpinnings of anxiety- and trauma-related mental health dis- orders, such as posttraumatic stress and panic disorder.


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 = $520,820 )
2024	2024	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Mental Health Research Grants	001	5	2/26/2024	SUPPLEMENT FOR EXPANSION	$76,068
2024	2024	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Mental Health Research Grants	000	5	1/8/2024	NON-COMPETING CONTINUATION	$400,278
2024	2024	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Mental Health Research Grants	002	5	7/5/2024	NON-COMPETING CONTINUATION	$44,474
														Subtotal = $520,820

Issue Date FY: 2023 ( Subtotal = $520,820 )
2023	2023	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Mental Health Research Grants	001	4	2/23/2023	NON-COMPETING CONTINUATION	$44,474
2023	2023	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Mental Health Research Grants	000	4	12/16/2022	NON-COMPETING CONTINUATION	$400,278
2023	2023	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Mental Health Research Grants	002	4	2/23/2023	SUPPLEMENT FOR EXPANSION	$76,068
														Subtotal = $520,820

Issue Date FY: 2022 ( Subtotal = $444,752 )
2022	2022	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Mental Health Research Grants	000	3	12/11/2021	NON-COMPETING CONTINUATION	$400,278
2022	2022	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Mental Health Research Grants	001	3	6/7/2022	NON-COMPETING CONTINUATION	$44,474
														Subtotal = $444,752

Issue Date FY: 2021 ( Subtotal = $444,752 )
2021	2021	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Mental Health Research Grants	000	2	12/17/2020	NON-COMPETING CONTINUATION	$400,277
2021	2021	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Mental Health Research Grants	001	2	4/21/2021	NON-COMPETING CONTINUATION	$44,475
														Subtotal = $444,752

Issue Date FY: 2020 ( Subtotal = $462,894 )
2020	2020	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Mental Health Research Grants	000	1	2/25/2020	NEW	$462,894
														Subtotal = $462,894

Grand Total All Awards = $2,394,038

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Neural circuits regulating flight and panic behavior.

Award Number: R01MH122561

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/01/2020

PERIOD OF PERFORMANCE END DATE: 12/31/2024

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