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Neurobiological mechanisms for transient forgetting

Award Number: F31MH123022
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 03/01/2020
PERIOD OF PERFORMANCE END DATE: 05/25/2022

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Neurobiological mechanisms for transient forgetting - Project Summary/Abstract Forgetting is a dynamic and intrinsic cognitive process that allows humans and animals to make rapid and flexible behavioral choices. Imbalances in memory stability/retrieval vs forgetting may result in detrimental pathologies common in many neurological and psychiatric disorders. The neuroscience of active forgetting is underexplored; historically, experimental psychology studies have frequently posited forgetting as passive. Yet, recent findings in Drosophila challenge this notion and illustrate that forgetting is also active. One form of active forgetting, termed intrinsic forgetting, engages a small group of protocerebral posterior lateral 1 dopamine neurons (PPL1 DAn). The PPL1 DAn slowly and chronically erase labile olfactory memories after learning, but potently remove them when the neurons are stimulated. Two critical questions that remain unexplored is whether the forgetting signal from these DAns also impair the expression of consolidated protein-synthesis dependent long-term memories (PSD-LTM), and whether the impairment is due to memory erasure or a transient block in retrieval. My preliminary studies indicate that stimulating a single PPL1 DAn transiently inhibits the retrieval of PSD-LTM. Currently, knowledge about the neurobiological mechanisms that lead to transient forgetting does not exist. Thus, my initial observations offer the first entrée, to our knowledge, of potential mechanisms that underly transient forgetting. This proposal is aimed to address these knowledge gaps. The overarching hypothesis is that transient forgetting is intrinsic to the fly’s memory management system and that factors extrinsic to the fly, such as interfering stimuli, can trigger the forgetting network to modulate the retrieval of PSD-LTM. To support my hypothesis, I will incorporate detailed behavioral and in vivo functional imaging assays, combined with multiple sophisticated genetic manipulations and novel paradigm designs. From Aim 1, I will confirm and extend my preliminary data indicating that only a single DAn in each brain hemisphere is responsible for transient forgetting. The data will reveal the minimal DAn components that are required for transient forgetting, which is essential for deeper experiments and to provide complete experimenter control over transient forgetting. From Aim 2, I will obtain data that will uncover the key DA receptor mediating the DAn-forgetting signal. Excitingly, I will identify the widely unchartered LTM cellular traces 3 days after spaced training and assay how these profiles change upon activating the DAn-forgetting pathway. These data may provide the molecular- and cellular-circuit based mechanisms that underscore transient forgetting. Lastly, from Aim 3, I will identify and characterize the extrinsic factors essential to induce top-down memory suppression to trigger transient memory loss. In sum, the outcomes of my proposed experiments will be the first to characterize the underlying extrinsic and intrinsic mechanisms that mobilize the DAn-forgetting pathway to cause transient memory loss.


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: 2023 ( Subtotal = -$24,661 )
2023	2022	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	001	3	5/15/2023	NON-COMPETING CONTINUATION	$0
2023	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	000	4	1/24/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$23,161
2023	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	002	4	5/15/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$1,500
														Subtotal = -$24,661

Issue Date FY: 2022 ( Subtotal = $33,036 )
2022	2022	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	001	3	3/28/2022	NON-COMPETING CONTINUATION	-$30,533
2022	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	002	4	3/28/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$30,533
2022	2022	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	000	3	2/10/2022	NON-COMPETING CONTINUATION	$33,036
														Subtotal = $33,036

Issue Date FY: 2021 ( Subtotal = $33,036 )
2021	2021	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	000	2	2/23/2021	NON-COMPETING CONTINUATION	$33,036
														Subtotal = $33,036

Issue Date FY: 2020 ( Subtotal = $32,520 )
2020	2020	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	001	1	2/18/2020	NEW	$0
2020	2020	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	000	1	2/18/2020	NEW	$32,520
														Subtotal = $32,520

Grand Total All Awards = $73,931

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Neurobiological mechanisms for transient forgetting

Award Number: F31MH123022

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 03/01/2020

PERIOD OF PERFORMANCE END DATE: 05/25/2022

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