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Real-Time Measurements of Neurotransmission in Drosphilia melanogaster

Award Number: R01MH085159
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/15/2009
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Real-Time Measurements of Neurotransmission in Drosphilia melanogaster - PROJECT SUMMARY How does neuronal signaling control behavior? Neuroscientists answer this question by mapping neuronal circuits, studying action potential firing, or monitoring the resultant neurochemicals released. Drosophila is a model system used to map neural circuits and study cell firing during innate behaviors, such as feeding. Direct measurements of neuromodulators are required to understand behavioral regulation because release is highly heterogeneous and plastic; i.e. the same firing patterns elicit different neuromodulator release in different circumstances due to complex regulation. To understand how neuromodulation regulates behavior or encodes memories, we need tools to examine multiple neuromodulators throughout a circuit. The goal of this project is to develop new multiplexed tools to study neuromodulator interactions in Drosophila during sugar feeding. The central hypothesis is that dopamine, octopamine, and glutamate neuromodulation will occur only in discrete neuropil, vary with frequency of sugar feeding, and be enhanced when sugar is paired with odors. This research is significant because it will develop tools to map real-time signaling of multiple neuromodulators throughout a circuit and use these tools to show how neuromodulator interactions in a circuit control appetitive memory formation during sugar feeding. In Aim 1, we will develop new nanoelectrodes to co-detect octopamine and dopamine using fast-scan cyclic voltammetry (FSCV) and measure them in the mushroom body (MB) g5 compartment during sugar feeding. Octopamine modulation of dopamine will be tested by selectively activating or suppressing a specific octopaminergic neuron. In Aim 2, the goal is to understand dopamine neuromodulation during sugar feeding across compartments of the MB. A genetically-encoded dopamine sensor (GRABDA) will be selectively expressed in either MB dopamine neurons or the protocerebral anterior medial (PAM) projection neurons and dopamine recorded during sugar feeding and olfactory conditioning. In Aim 3, neuromodulation will be mapped throughout a circuit that regulates sugar reward by measuring dopamine and octopamine in the g5 compartment of the mushroom body and glutamate signaling (iGluSnFR) from a mushroom body output neuron in the superior medial protocerebrum. These experiments will be the first to multiplex FSCV and genetically encoded sensors to understand how dopamine/octopamine regulation in the mushroom body controls output signaling downstream in a circuit. The expected outcomes of this work are mapping of neuromodulator interactions throughout a circuit in adult Drosophila during feeding and olfactory conditioning. The positive impact will be advanced methods and foundational knowledge necessary to perform future studies of how genetics, behavior, or disease alter neuromodulator release. The neuromodulators studied here are implicated in mental health disorders, such as schizophrenia, compulsive eating, or addiction, and this work facilitates using Drosophila as a model organism for studying neuromodulation in neurological diseases.


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 = $365,388 )
2025	2025	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Mental Health Research Grants	000	14	4/8/2025	NON-COMPETING CONTINUATION	$365,388
														Subtotal = $365,388

Issue Date FY: 2024 ( Subtotal = $429,867 )
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Mental Health Research Grants	001	13	8/15/2024	NON-COMPETING CONTINUATION	$42,987
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Mental Health Research Grants	000	13	3/19/2024	NON-COMPETING CONTINUATION	$386,880
														Subtotal = $429,867

Issue Date FY: 2023 ( Subtotal = $429,867 )
2023	2023	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Mental Health Research Grants	000	12	3/22/2023	NON-COMPETING CONTINUATION	$429,867
														Subtotal = $429,867

Issue Date FY: 2022 ( Subtotal = $465,287 )
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Mental Health Research Grants	000	11	4/25/2022	COMPETING CONTINUATION	$465,287
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Mental Health Research Grants	002	11	9/7/2022	COMPETING CONTINUATION	$0
2022	2020	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Mental Health Research Grants	001	10	9/7/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $465,287

Issue Date FY: 2020 ( Subtotal = $376,225 )
2020	2020	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Mental Health Research Grants	000	10	2/4/2020	NON-COMPETING CONTINUATION	$376,225
														Subtotal = $376,225

Issue Date FY: 2019 ( Subtotal = $377,287 )
2019	2019	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Mental Health Research Grants	000	9	3/4/2019	NON-COMPETING CONTINUATION	$377,287
														Subtotal = $377,287

Issue Date FY: 2018 ( Subtotal = $378,290 )
2018	2018	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Mental Health Research Grants	000	8	3/9/2018	NON-COMPETING CONTINUATION	$340,461
2018	2018	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Mental Health Research Grants	001	8	6/4/2018	NON-COMPETING CONTINUATION	$37,829
														Subtotal = $378,290

Issue Date FY: 2017 ( Subtotal = $379,236 )
2017	2017	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Mental Health Research Grants	000	7	3/1/2017	NON-COMPETING CONTINUATION	$341,312
2017	2017	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Mental Health Research Grants	001	7	7/18/2017	NON-COMPETING CONTINUATION	$37,924
														Subtotal = $379,236

Issue Date FY: 2016 ( Subtotal = $338,685 )
2016	2016	UNIVERSITY OF VIRGINIA	P.O. BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Mental Health Research Grants	000	6	5/13/2016	COMPETING CONTINUATION	$338,685
														Subtotal = $338,685

Issue Date FY: 2013 ( Subtotal = $357,897 )
2013	2013	UNIVERSITY OF VIRGINIA	P.O. BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Mental Health Research Grants	001	5	9/4/2013	NON-COMPETING CONTINUATION	$22,368
2013	2013	UNIVERSITY OF VIRGINIA	P.O. BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Mental Health Research Grants	000	5	5/5/2013	NON-COMPETING CONTINUATION	$335,529
														Subtotal = $357,897

Issue Date FY: 2012 ( Subtotal = $373,568 )
2012	2012	UNIVERSITY OF VIRGINIA	P.O. BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Mental Health Research Grants	000	4	3/16/2012	NON-COMPETING CONTINUATION	$373,568
														Subtotal = $373,568

Issue Date FY: 2011 ( Subtotal = $371,287 )
2011	2011	UNIVERSITY OF VIRGINIA	P.O. BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Mental Health Research Grants	000	3	7/8/2011	NON-COMPETING CONTINUATION	$371,287
														Subtotal = $371,287

Issue Date FY: 2010 ( Subtotal = $372,139 )
2010	2010	UNIVERSITY OF VIRGINIA	P.O. BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Mental Health Research Grants	001	2	5/26/2010	NON-COMPETING CONTINUATION	$367,535
2010	2009	UNIVERSITY OF VIRGINIA	P.O. BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Mental Health Research Grants	000	1	12/14/2009	NEW	$4,604
														Subtotal = $372,139

Issue Date FY: 2009 ( Subtotal = $344,843 )
2009	2009	UNIVERSITY OF VIRGINIA	P.O. BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Mental Health Research Grants	000	1	7/2/2009	NEW	$344,843
														Subtotal = $344,843

Grand Total All Awards = $5,359,866

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Real-Time Measurements of Neurotransmission in Drosphilia melanogaster

Award Number: R01MH085159

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/15/2009

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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