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Investigating dopamine's role in olfactory navigation

Award Number: F30DC023130
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 04/01/2025
PERIOD OF PERFORMANCE END DATE: 03/31/2029

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Investigating dopamine's role in olfactory navigation - Project Summary Olfaction is the primary sensory modality that many animals use to navigate. However, navigating through the chemical world is inherently challenging due to the complexity of odor plumes, which can vary in both composition and concentration. Tracking a plume to its source therefore requires the integration of complex sensory cues with continuous spatial decision-making, posing a distinct challenge to the flexibility of the nervous system. Dopamine has been extensively studied as a neuromodulator that confers flexibility to nervous systems, yet the anatomical heterogeneity and genetic inaccessibility of mammalian dopaminergic systems have precluded a detailed understanding of dopamine’s role at the molecular and circuit level. In comparison, the simple neural architecture and genetic tractability of Drosophila melanogaster provide an exceptional model to study the role of dopaminergic modulation during flexible, naturalistic behaviors like olfactory navigation, as flies robustly track odor plumes using neural circuits that are both genetically accessible and comprehensively mapped at synaptic resolution. In preliminary data, I demonstrated that dopamine neurons in the Drosophila mushroom body, an associative brain center essential for olfactory learning and memory, are continuously engaged during olfactory navigation and can rapidly and bidirectionally bias a fly’s navigational strategy. I also showed that Kenyon cells, the post-synaptic targets of dopaminergic modulation whose activity is required for associative plasticity in the mushroom body, are also required for sustained olfactory pursuit. Using in vivo two-photon imaging, I showed that the strength of signaling from mushroom body output neurons can be rapidly modulated as flies navigate within a virtual olfactory landscape. These results support the hypothesis that the same dopaminergic plasticity mechanisms underlying associative learning are also continuously engaged to regulate and dynamically shape ongoing olfactory navigation. In Aim 1, I will leverage in vivo two-photon imaging and optogenetic perturbations of neural activity to define both correlational and causal relationships between the activity of dopamine neurons and their downstream mushroom body output neurons. In Aim 2, I will use a targeted genetic knockdown strategy in combination with optogenetics to identify the dopamine receptor signaling pathways mediating dopaminergic modulation during olfactory navigation. Together, these studies will provide an updated framework for understanding how dopamine dynamics can flexibly guide naturalistic behaviors like navigation, in circuits with fully characterized cell types and synaptic connections.


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 = $55,114 )
2026	2026	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Research Related to Deafness and Communication Disorders	000	2	3/24/2026	NON-COMPETING CONTINUATION	$54,538
2026	2026	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Research Related to Deafness and Communication Disorders	001	2	3/26/2026	NON-COMPETING CONTINUATION	$576
														Subtotal = $55,114

Issue Date FY: 2025 ( Subtotal = $54,538 )
2025	2025	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Research Related to Deafness and Communication Disorders	001	1	3/25/2025	NEW	$0
2025	2025	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Research Related to Deafness and Communication Disorders	002	1	6/13/2025	NEW	$564
2025	2025	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Research Related to Deafness and Communication Disorders	000	1	3/25/2025	NEW	$53,974
														Subtotal = $54,538

Grand Total All Awards = $109,652

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Investigating dopamine's role in olfactory navigation

Award Number: F30DC023130

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 04/01/2025

PERIOD OF PERFORMANCE END DATE: 03/31/2029

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