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The Receptor Basis for Serotonergic Modulation of Olfaction Across Multiple BrainAreas

Award Number: R01DC016293
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary. Sensory networks continuously fine-tune how they process information to meet ongoing physiological demands. The nervous system achieves this flexibility via the release of “neuromodulators” which alter the biophysical and synaptic properties of individual neuron classes within a network. This adjusts the influence of each class to optimize network dynamics for the appropriate context. Neuromodulation is ubiquitous and many neurological disorders result from, or are associated with, dysfunctional neuromodulatory systems. Despite the importance of neuromodulation for healthy sensory processing, our ability to predict the consequences of neuromodulation is limited by the diversity of modulatory receptors expressed by different classes of neurons. Each receptor has different effects and each class of neuron supports different features of sensory coding, so the effects of neuromodulation can be complex. We propose to address this issue in a genetically tractable model with fewer neurons and modulatory receptors; the olfactory system of Drosophila. The objective of this application is to determine how serotonin (5-HT) receptor subtypes affect key neuronal classes and the consequences for olfactory processing and odor-guided behavior. The long-term goal of this research is to determine the mechanistic basis for neuromodulation of sensory network dynamics. In vertebrate and invertebrate olfactory systems, the effects of 5-HT on odor-evoked responses vary across different neuron classes. However, it is difficult to determine how 5-HT alters olfactory processing without knowing the consequences of activating the 5-HT receptors expressed by each class. We recently completed a comprehensive atlas of 5-HT receptor expression within the olfactory system, so we now propose to manipulate the expression of individual 5-HT receptors in specific classes of neurons to determine how 5-HT affects individual neuron classes, the consequences for odor coding across olfactory brain regions and odor- guided behavior. In addition, we will use one of the first whole brain, nanometer resolution EM connectomes to establish single cell resolution connectivity rules of 5-HT neurons with each olfactory neuron class examined in this proposal. In Specific Aim 1 we will determine the receptor basis for the effects of 5-HT on local inhibitory networks within the first olfactory neuropil (the antennal lobe or “AL”). In Aim 2 we will determine the contribution of direct modulation of cholinergic AL output neurons to the overall effects of 5-HT on olfactory information sent to downstream processing stages. Finally, in Aim 3 we will determine how 5-HT receptors modulate GABAergic AL output neurons that promote olfactory attraction. These experiments will establish how the overall effects of 5-HT emerge from neuron class-specific expression of 5-HT receptors, thus addressing a critical gap in our knowledge of healthy sensory processing.


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: 2022 ( Subtotal = $382,762 )
2022	2022	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE	MORGANTOWN	WV	26506	MONONGALIA	USA	Research Related to Deafness and Communication Disorders	001	5	6/2/2022	SUPPLEMENT FOR EXPANSION	$69,737
2022	2022	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE	MORGANTOWN	WV	26506	MONONGALIA	USA	Research Related to Deafness and Communication Disorders	000	5	5/24/2022	NON-COMPETING CONTINUATION	$382,762
2022	2022	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE	MORGANTOWN	WV	26506	MONONGALIA	USA	Research Related to Deafness and Communication Disorders	002	5	8/29/2022	SUPPLEMENT FOR EXPANSION	-$69,737
														Subtotal = $382,762

Issue Date FY: 2021 ( Subtotal = $460,537 )
2021	2021	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE	MORGANTOWN	WV	26506	MONONGALIA	USA	Research Related to Deafness and Communication Disorders	000	4	5/10/2021	NON-COMPETING CONTINUATION	$390,514
2021	2021	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE	MORGANTOWN	WV	26506	MONONGALIA	USA	Research Related to Deafness and Communication Disorders	001	4	7/21/2021	SUPPLEMENT FOR EXPANSION	$70,023
														Subtotal = $460,537

Issue Date FY: 2020 ( Subtotal = $390,514 )
2020	2020	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE	MORGANTOWN	WV	26506	MONONGALIA	USA	Research Related to Deafness and Communication Disorders	000	3	5/20/2020	NON-COMPETING CONTINUATION	$390,514
														Subtotal = $390,514

Issue Date FY: 2019 ( Subtotal = $391,300 )
2019	2019	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE	MORGANTOWN	WV	26506	MONONGALIA	USA	Research Related to Deafness and Communication Disorders	000	2	5/10/2019	NON-COMPETING CONTINUATION	$391,300
														Subtotal = $391,300

Issue Date FY: 2018 ( Subtotal = $449,278 )
2018	2018	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE	MORGANTOWN	WV	26506	MONONGALIA	USA	Research Related to Deafness and Communication Disorders	000	1	5/29/2018	NEW	$449,278
														Subtotal = $449,278

Grand Total All Awards = $2,074,391

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The Receptor Basis for Serotonergic Modulation of Olfaction Across Multiple BrainAreas

Award Number: R01DC016293

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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