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Alcohol and Developing Neuronal Circuits

Award Number: R01AA015614
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2005
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Alcohol and Developing Neuronal Circuits - Project Summary / Abstract Cognitive function deficits are among the most devastating consequences of fetal alcohol exposure. Currently available treatments against these deficits have limited efficacy. Our long-term goal is to identify specific functional mechanisms underlying the cognitive deficits associated with FASDs, so that circuit-specific treatments can be developed to prevent and correct them. Our objective is to leverage both in vitro and in vivo electrophysiological approaches to determine the long-term impact of third trimester-equivalent ethanol exposure (TTAE) on the limbic memory system. Our central hypothesis is that TTAE disrupts the balance of excitatory and inhibitory synaptic transmission at hippocampal formation→retrosplenial cortex (RSC) and RSC↔anterior thalamic nucleus (ATN) synapses, leading to deficits in information flow within and between these brain regions. Our rationale for the use of complementary in vitro and in vivo electrophysiological approaches is to provide a multi- scale view of the effects of TTAE on functional hippocampal CA1, subiculum (SUB), RSC and ATN connectivity. In Aim 1, we will determine the effects of TTAE on the function of CA1→RSC and SUB→RSC pathways. We will use slice electrophysiology, retrograde labeling, and optogenetics to test the hypothesis that TTAE persistently reduces glutamatergic transmission at SUB→RSC synapses, and increases direct monosynaptic long-range inhibition (CA1→RSC) and indirect feedforward di-synaptic inhibition (SUB→RSC interneurons→RSC pyramidal neurons). We will also use high-density silicone electrode recordings in freely behaving mice to test the hypothesis that ethanol exposure reduces the number, efficiency, and information content of high frequency oscillatory bursts in the RSC that are important for memory. In Aim 2, we will determine the effects of TTAE on the function of ATN↔RSC pathways. We will test the hypothesis that TTAE persistently reduces glutamatergic transmission at reciprocal monosynaptic connections between the ATN and RSC, without affecting di-synaptic feedforward inhibition at RSC→thalamic reticular nuclei→ATN synapses. We will also test the hypothesis that TTAE disrupts the activity of ATN and RSC neurons specifically modulated by an animal’s head direction that are essential in spatial learning and memory. The research proposed in this application is innovative because it will systematically characterize, for the first time, the developmental effects of ethanol on interactions among key components of the limbic memory network. The proposed research is significant because it will elucidate novel functional neurobiological mechanisms underlying developmental ethanol exposure- induced cognitive deficits, and identify specific biological targets for interventions to ameliorate them.


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 = $521,566 )
2025	2025	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Alcohol Research Programs	000	19	8/11/2025	NON-COMPETING CONTINUATION	$521,566
														Subtotal = $521,566

Issue Date FY: 2024 ( Subtotal = $521,566 )
2024	2024	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Alcohol Research Programs	000	18	7/19/2024	NON-COMPETING CONTINUATION	$521,566
														Subtotal = $521,566

Issue Date FY: 2023 ( Subtotal = $556,002 )
2023	2023	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Alcohol Research Programs	001	17	8/15/2023	NON-COMPETING CONTINUATION	$521,566
2023	2022	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Alcohol Research Programs	000	16	6/1/2023	COMPETING CONTINUATION	$34,436
														Subtotal = $556,002

Issue Date FY: 2022 ( Subtotal = $521,566 )
2022	2022	UNIVERSITY OF NEW MEXICO	2500 MARBLE DR NE	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Alcohol Research Programs	001	16	9/7/2022	COMPETING CONTINUATION	$3,361
2022	2022	UNIVERSITY OF NEW MEXICO	2500 MARBLE DR NE	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Alcohol Research Programs	000	16	8/15/2022	COMPETING CONTINUATION	$518,205
														Subtotal = $521,566

Issue Date FY: 2011 ( Subtotal = $0 )
2011	2009	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Alcohol Research Programs	000	5	2/18/2011	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2009 ( Subtotal = $248,898 )
2009	2009	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Alcohol Research Programs	000	5	4/1/2009	NON-COMPETING CONTINUATION	$248,898
														Subtotal = $248,898

Issue Date FY: 2008 ( Subtotal = $248,898 )
2008	2008	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Alcohol Research Programs	000	4	3/18/2008	NON-COMPETING CONTINUATION	$248,898
														Subtotal = $248,898

Issue Date FY: 2007 ( Subtotal = $248,898 )
2007	2007	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Alcohol Research Programs	000	3	3/19/2007	NON-COMPETING CONTINUATION	$248,898
														Subtotal = $248,898

Issue Date FY: 2006 ( Subtotal = $256,332 )
2006	2006	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Alcohol Research Programs	000	2	3/30/2006	NON-COMPETING CONTINUATION	$256,332
														Subtotal = $256,332

Issue Date FY: 2005 ( Subtotal = $262,500 )
2005	2005	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Alcohol Research Programs	000	1	3/28/2005	NEW	$262,500
														Subtotal = $262,500

Grand Total All Awards = $3,386,226

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Alcohol and Developing Neuronal Circuits

Award Number: R01AA015614

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2005

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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