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Neural Circuits Underlying Adaptive Behavior and Addiction

Award Number: R01DA030601
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/15/2011
PERIOD OF PERFORMANCE END DATE: 06/30/2016

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Neural Circuits Underlying Adaptive Behavior and Addiction - DESCRIPTION (provided by applicant): Learning requires the updating of predictions based on experience, a process thought to be driven by error signals carried by dopaminergic neurons. The short-circuiting of this process by many drugs of abuse is an important factor in addiction. Despite this, the neural circuits that calculate changes in expectation and act upon conditioning dopamine signals remain largely unknown. As in mammals, dopamine plays an instructive role in the adaptive behavior of the fly, Drosophila melanogaster. We have previously identified a subset of dopaminergic neurons sufficient to provide conditioning error signals during olfactory learning, and have anatomically mapped the source of reinforcement to a single cluster of 12 cells, the PPL1 neurons. This project will take advantage of the numerical simplicity and genetic tractability of the fly brain and use the PPL1 cluster as the point of entry into the conserved mechanisms underlying adaptive behavior. Using a combination of genetic, neuroanatomical and optogenetic approaches along with functional optical imaging, electrophysiology and behavioral analysis, we will address four Specific Aims: 1) We will target optogenetic tools to restricted subsets of PPL1 neurons and establish which cells are necessary, and which sufficient, to drive learning. 2) We will use optical and electrophysiological recordings to monitor the activity of PPL1 neurons before, during, and after learning, allowing us to test the hypothesis that PPL1 output represents a prediction error signal. The effect of cocaine, methylphenidate, and amphetamine on this learning process will be determined, revealing the effects of these drugs of abuse on an identified learning circuit. 3) We will trace PPL1 projections to the storage sites of associative memories, analyze the biophysical changes underlying memory formation, and identify the circuit components that relay the contents of memory to downstream decision-making centers. 4) We will identify and manipulate synaptic inputs to PPL1 neurons in an effort to dissect the biological algorithm that regulates dopamine release. The project thus addresses fundamental questions about the neural principles underpinning adaptive behavior and addiction, using powerful new technologies in an eminently tractable experimental system.


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: 2021 ( Subtotal = -$85,505 )
2021	2015	UNIVERSITY OF OXFORD	UNIVERSITY OFFICES	OXFORD	OXFORDSHIRE			GBR	Drug Use and Addiction Research Programs	002	5	10/3/2020	NON-COMPETING CONTINUATION	-$85,505
2021	2015	UNIVERSITY OF OXFORD	UNIVERSITY OFFICES	OXFORD	OXFORDSHIRE			GBR	Drug Use and Addiction Research Programs	000	5	10/1/2020	NON-COMPETING CONTINUATION	-$85,505
2021	2015	UNIVERSITY OF OXFORD	UNIVERSITY OFFICES	OXFORD	OXFORDSHIRE			GBR	Drug Use and Addiction Research Programs	001	5	10/3/2020	NON-COMPETING CONTINUATION	$85,505
														Subtotal = -$85,505

Issue Date FY: 2017 ( Subtotal = -$4,345 )
2017	2015	UNIVERSITY OF OXFORD	UNIVERSITY OFFICES	OXFORD	OXFORDSHIRE	OX1 2JD		GBR	Drug Use and Addiction Research Programs	000	5	12/1/2016	NON-COMPETING CONTINUATION	-$4,345
														Subtotal = -$4,345

Issue Date FY: 2015 ( Subtotal = $237,546 )
2015	2015	OXFORD UNIVERSITY, DEPT OF BIOCHEMISTRY & GENETICS LAB	UNIVERSITY OFFICES	OXFORD				GBR	Drug Use and Addiction Research Programs	000	5	6/9/2015	NON-COMPETING CONTINUATION	$237,546
														Subtotal = $237,546

Issue Date FY: 2014 ( Subtotal = $241,371 )
2014	2014	OXFORD UNIVERSITY, DEPT OF BIOCHEMISTRY & GENETICS LAB	UNIVERSITY OFFICES	OXFORD				GBR	Drug Use and Addiction Research Programs	000	4	6/19/2014	NON-COMPETING CONTINUATION	$241,371
														Subtotal = $241,371

Issue Date FY: 2013 ( Subtotal = $231,922 )
2013	2013	OXFORD UNIVERSITY, DEPT OF BIOCHEMISTRY & GENETICS LAB	SOUTH PARK ROAD	OXFORD				GBR	Drug Use and Addiction Research Programs	002	3	6/18/2013	EXTENSION WITH OR WITHOUT FUNDS	$231,922
2013	2012	OXFORD UNIVERSITY, DEPT OF BIOCHEMISTRY & GENETICS LAB	UNIVERSITY OFFICES	OXFORD		00000		GBR	Drug Use and Addiction Research Programs	001	2	11/16/2012	NON-COMPETING CONTINUATION	$0
2013	2011	OXFORD UNIVERSITY, DEPT OF BIOCHEMISTRY & GENETICS LAB	UNIVERSITY OFFICES	OXFORD		00000		GBR	Drug Use and Addiction Research Programs	000	1	11/16/2012	NEW	$0
														Subtotal = $231,922

Issue Date FY: 2012 ( Subtotal = $241,788 )
2012	2012	OXFORD UNIVERSITY, DEPT OF BIOCHEMISTRY & GENETICS LAB	SOUTH PARK ROAD	OXFORD				GBR	Drug Use and Addiction Research Programs	001	2	6/19/2012	NON-COMPETING CONTINUATION	$241,788
2012	2011	OXFORD UNIVERSITY, DEPT OF BIOCHEMISTRY & GENETICS LAB	SOUTH PARK ROAD	OXFORD		00000		GBR	Drug Use and Addiction Research Programs	000	1	6/13/2012	NEW	$0
														Subtotal = $241,788

Issue Date FY: 2011 ( Subtotal = $238,821 )
2011	2011	OXFORD UNIVERSITY, DEPT OF BIOCHEMISTRY & GENETICS LAB	SOUTH PARK ROAD	OXFORD				GBR	Drug Use and Addiction Research Programs	000	1	7/5/2011	NEW	$238,821
														Subtotal = $238,821

Grand Total All Awards = $1,101,598

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Neural Circuits Underlying Adaptive Behavior and Addiction

Award Number: R01DA030601

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/15/2011

PERIOD OF PERFORMANCE END DATE: 06/30/2016

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