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Understanding functional connectivity of sensory and motor pathways to specific regions of the lower urinary tract.

Award Number: OT2OD023872
ORGANIZATION: OFFICE OF THE DIRECTOR, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: OTHER
PERIOD OF PERFORMANCE START DATE: 09/28/2016
PERIOD OF PERFORMANCE END DATE: 07/31/2024

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Understanding functional connectivity of sensory and motor pathways to specific regions of the lower urinary tract. - ABSTRACT This foundational project will produce mesoscopic and microscopic functional anatomical maps of the sensory and autonomic (motor) neurons that regulate the lower urinary tract (LUT). Neural dysfunction is a major contributor to diverse, largely intractable urological problems, including overactive or underactive bladder, incontinence due to ageing or pelvic surgery, and painful bladder syndrome/interstitial cystitis. We will fill knowledge gaps and overcome diverse technical roadblocks to develop maps that provide a critical foundation for modeling different LUT behaviors, understanding neuromodulatory mechanisms, and determining off-target effects of neuromodulation. We will conduct this study in adult rats, the species where the peripheral and spinal circuitry of the LUT is defined in the most detail and, compared with mice, their larger size facilitates development of devices. Together, this will facilitate development of new methods for normalizing over- or underactivity in these circuits. The aims to be addressed in males and females are: (1) To map functionally distinct classes of sensory and autonomic neurons that innervate the bladder body, trigone and proximal urethra. We will also map neurons that project to more than one of these regions (`cross-talk'). In addition to known functional markers of sensory and autonomic neural subtypes, we will use the latest outcomes of our RNA-seq analyses of retrogradely labeled bladder-projecting neurons to define and map new markers of functional subclasses. (2) To map the spinal targets of sensory neurons innervating the bladder body, trigone and proximal urethra. Using viral tracing we will map and characterize second order sensory neurons in autonomic reflex and nociceptive pathways; we will also identify sites of convergence from two peripheral targets. (3) To map the spinal neurons activated by physiologically- or electrically-induced voiding in conscious rats. Our recent advance of activating pelvic nerves in chronically- catheterized conscious animals will be combined with markers of neural activation, detailed phenotyping of activated neurons and viral tracing.


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 = $0 )
2025	2021	UNIVERSITY OF MELBOURNE	RAYMOND PRIESTLEY BLDG UNIV OF MELB	MELBOURNE	VICTORIA			AUS	Trans-NIH Research Support	000	1	10/8/2024	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC			AUS	Trans-NIH Research Support	001	1	6/6/2023	SUPPLEMENT FOR EXPANSION	$0
2023	2021	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC			AUS	Trans-NIH Research Support	000	1	1/31/2023	SUPPLEMENT FOR EXPANSION	$0
2023	2021	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC			AUS	Trans-NIH Research Support	002	1	7/31/2023	SUPPLEMENT FOR EXPANSION	$0
2023	2016	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC			AUS	Trans-NIH Research Support	003	1	9/27/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC			AUS	Trans-NIH Research Support	001	1	6/23/2022	SUPPLEMENT FOR EXPANSION	$0
2022	2016	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC			AUS	Trans-NIH Research Support	000	1	6/22/2022	NEW	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $1,474,654 )
2021	2021	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC			AUS	Trans-NIH Research Support	003	1	7/27/2021	SUPPLEMENT FOR EXPANSION	$0
2021	2021	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC			AUS	Trans-NIH Research Support	002	1	7/12/2021	SUPPLEMENT FOR EXPANSION	$1,474,654
2021	2020	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC			AUS	Trans-NIH Research Support	001	1	7/12/2021	SUPPLEMENT FOR EXPANSION	$0
2021	2016	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC			AUS	Trans-NIH Research Support	000	1	7/12/2021	NEW	$0
														Subtotal = $1,474,654

Issue Date FY: 2018 ( Subtotal = $707,588 )
2018	2018	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC	3052		AUS	Trans-NIH Research Support	001	1	8/8/2018	SUPPLEMENT FOR EXPANSION	$707,588
2018	2016	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC	3052		AUS	Trans-NIH Research Support	000	1	8/8/2018	NEW	$0
														Subtotal = $707,588

Issue Date FY: 2017 ( Subtotal = $452,854 )
2017	2017	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC	3052		AUS	Trans-NIH Research Support	000	1	7/31/2017	SUPPLEMENT FOR EXPANSION	$452,854
														Subtotal = $452,854

Issue Date FY: 2016 ( Subtotal = $524,589 )
2016	2016	UNIVERSITY OF MELBOURNE	**	MELBOURNE				AUS	Trans-NIH Research Support	000	1	9/28/2016	NEW	$524,589
														Subtotal = $524,589

Grand Total All Awards = $3,159,685

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Understanding functional connectivity of sensory and motor pathways to specific regions of the lower urinary tract.

Award Number: OT2OD023872

ORGANIZATION: OFFICE OF THE DIRECTOR, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: OTHER

PERIOD OF PERFORMANCE START DATE: 09/28/2016

PERIOD OF PERFORMANCE END DATE: 07/31/2024

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