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Dissecting isoflurane-activated ventral subiculum circuitry

Award Number: F32GM167225
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 03/15/2027
PERIOD OF PERFORMANCE END DATE: 03/14/2028

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Dissecting isoflurane-activated ventral subiculum circuitry - PROJECT SUMMARY Approximately 60,000 Americans undergo surgery daily, yet emergence from general anesthesia remains unpredictable and can lead to complications like delayed consciousness recovery and delirium. Postoperative delirium affects up to 50-70% of young and elderly patients undergoing complex procedures, highlighting a need for interventions facilitating smooth emergence with fewer cognitive side effects. Isoflurane anesthesia, even in the absence of surgery, impairs cellular integrity of the hippocampus leading to functional deficits in hippocampal-dependent behaviors including spatial memory and contextual fear learning. While ageing increases vulnerability to cognitive impairments following general anesthesia, most preclinical studies have focused only on the effects of isoflurane exposure on hippocampal function in neonates. The hippocampus plays a key role in cognitive tasks including memory consolidation, spatial navigation, and emotional regulation. Notably, neuronal activity in the ventral subiculum (vSub), which processes key hippocampal outputs for memory consolidation, was recently identified to contribute to arousal. vSub inputs from the hippocampus, thalamus, entorhinal cortex, medial septum, and amygdala regulate motivation, arousal, and memory processing, domains critically affected by anesthesia and delirium. Preliminary data shows vSub activation by isoflurane, yet the direct relationship of vSub circuitry with anesthetic action is unknown. I aim to test the hypothesis that modulating vSub neural circuitry may accelerate emergence and improve post-anesthetic cognitive function by employing two complementary approaches that utilize cutting-edge neuroscience approaches. In Aim 1, I will characterize the functional role of vSub circuit modulation on GA sensitivity and post- anesthetic behavior across the lifespan using chemogenetics. Stereotaxic viral delivery of Cre-dependent activating/inhibiting DREADDs in vSub will enable selective modulation of vSub circuitry activated by isoflurane anesthesia to assess effects on cognitive behaviors. In Aim 2, I will characterize brain-wide vSub circuitry using viral tracing, intact brain clearing and immunolabeling to identify isoflurane-activated neural pathways with cellular resolution. These studies will elucidate how vSub circuitry influences anesthetic action and identify targets for improving post-anesthetic cognitive recovery across the lifespan.


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 = $76,780 )
2026	2026	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	000	1	9/15/2026	NEW	$76,780
														Subtotal = $76,780

Grand Total All Awards = $76,780

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Dissecting isoflurane-activated ventral subiculum circuitry

Award Number: F32GM167225

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 03/15/2027

PERIOD OF PERFORMANCE END DATE: 03/14/2028

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