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The Impact of Third Trimester Alcohol Exposure on Memories Encoded by Sharp-Wave Ripples of the Hippocampal-Retrosplenial Cortex Circuit

Award Number: F31AA031916
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/01/2024
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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The Impact of Third Trimester Alcohol Exposure on Memories Encoded by Sharp-Wave Ripples of the Hippocampal-Retrosplenial Cortex Circuit - Project Summary Fetal alcohol spectrum disorder (FASD), which occurs when a fetus is exposed to alcohol, is a neurodevelopmental disorder affecting up to 5% of the US population. One of the most devastating outcomes for children with FASD are learning and memory deficits, the mechanisms of which are little understood. Essential for learning and memory, sharp wave ripples (SWRs) are high frequency neural oscillatory events observed in the CA1 region of the hippocampus that travel to the retrosplenial cortex (RSC). Third trimester alcohol exposure (TTAE) in particular leads to severe neuronal death in the RSC and dysfunction in neuronal populations necessary for SWR formation. Despite this clear damage, little is known about how TTAE affects SWRs in the RSC. To fill this gap in knowledge, I propose the use of a mouse model of TTAE together with in vivo electrophysiology and optogenetics to investigate the effects on SWR characteristics across learning. Electrodes will be implanted in the CA1 and RSC, allowing for data collection while navigating a Barnes maze (BM) spatial navigation learning and memory task. Recordings will continue for 24 hours following the end of the task each day to gather SWRs that occur during Non-Rapid Eye Movement (NREM) sleep when memories are consolidated. Multiple analytical tools will be used to investigate the impact of TTAE on two key SWR features - amplitude and duration. Additional tools will be used to assess the firing rates and waveforms of individual neurons, to determine the impact of TTAE on the recruitment of excitatory versus inhibitory neurons by SWRs and the “replay” of these neurons during NREM. A separate and smaller subset of subjects will undergo optogenetic induction of SWRs, principally to evaluate if TTAE leads to alterations in SWR CA1 induction thresholds and/or propagation rates from CA1 to RSC. Collectively, this proposal will determine the functional mechanisms of key phases of learning and the role of SWRs to these phases: Acquisition, consolidation, retrieval and plasticity. The successful completion of this proposal will provide critical information on the lasting neurological impacts of TTAE on SWRs in the RSC, and how this may affect learning and memory. Additionally, this work will provide intensive training in awake/behaving electrophysiology, optogenetics, and a wide variety of analytical tools.


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: 2026 ( Subtotal = $40,703 )
2026	2026	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Alcohol Research Programs	000	3	7/27/2026	NON-COMPETING CONTINUATION	$40,703
														Subtotal = $40,703

Issue Date FY: 2025 ( Subtotal = $40,127 )
2025	2025	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Alcohol Research Programs	000	2	7/9/2025	NON-COMPETING CONTINUATION	$40,127
														Subtotal = $40,127

Issue Date FY: 2024 ( Subtotal = $39,563 )
2024	2024	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Alcohol Research Programs	000	1	7/26/2024	NEW	$39,563
2024	2024	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Alcohol Research Programs	001	1	7/26/2024	NEW	$0
														Subtotal = $39,563

Grand Total All Awards = $120,393

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The Impact of Third Trimester Alcohol Exposure on Memories Encoded by Sharp-Wave Ripples of the Hippocampal-Retrosplenial Cortex Circuit

Award Number: F31AA031916

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/01/2024

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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