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Peptidergic modulation of thermoregulation and energy expenditure

Award Number: R01NS094800
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2015
PERIOD OF PERFORMANCE END DATE: 02/28/2022

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Peptidergic modulation of thermoregulation and energy expenditure - ¿ DESCRIPTION (provided by applicant): Zona incerta (ZI) of the diencephalon has extensive connections with other brain regions and has been involved in several functions such as controlling visceral activity, thermoregulation, arousal and locomotor activity. In spite of its important functions it is one of the most understudied regions of the brain and no studies of the cellular and synaptic electrophysiological properties of ZI neurons have been reported so far. Maintenance of body temperature is central to energy homeostasis in mammals because it represents a major part of the energy expenditure of the organism. It is controlled by neurons of the preoptic area/ anterior hypothalamus (PO/AH) that project directly or indirectly to the rostral raphe pallidus. Anatomical and functional evidence clearly indicate a projection from the preoptic area, the thermoregulatory center, to ZI neurons. Combined retrograde labeling/immunostaining experiments have revealed that preoptic neurons projecting to ZI are peptidergic. ZI neurons project to the raphe pallidus and thus they can represent a relay of the preoptic thermogenic output to the brainstem neurons controlling thermoeffector processes. Our overarching hypothesis is that ZI GABAergic neurons mediate the peptidergic modulation of thermoregulation by PO/AH neurons. Preliminary data indicate that ZI neurons express receptors for these neuropeptides. We have also found that thermoregulatory neuropeptides excite ZI GABAergic neurons by activating inward currents and that they increase intracellular Ca concentrations. Our preliminary data also show that preoptic neurons projecting to ZI GABAergic neurons are peptidergic. Using transgenic models and telemetry we plan to study the role of ZI neurons in mediating the modulation of thermoregulation by neuropeptides (Sp Aim 1). We plan to identify thermoregulatory ZI neurons in slices and study their firing and synaptic characteristics as well as their modulation by neuropeptides involved in thermoregulation, followed by single cell RT/PCR analysis to determine the expression patterns for these receptors (Sp. Aim 2). By employing pharmacological tools, Ca imaging, electrophysiology and transgenic models we will then study the signaling pathways and the ion conductances involved in the neuropeptides' actions on ZI neurons (Sp. Aim 3). In summary in this study we will address fundamental and unexplored aspects of neural control of thermoregulation.


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 = $0 )
2022	2019	SCINTILLON INSTITUTE	6868 NANCY RIDGE DR	SAN DIEGO	CA	92121	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	8/15/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	SCINTILLON INSTITUTE,THE	6868 NANCY RIDGE DR	SAN DIEGO	CA	92121	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	9/8/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $532,691 )
2019	2019	SCINTILLON INSTITUTE,THE	6868 NANCY RIDGE DR	SAN DIEGO	CA	92121	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	7/24/2019	NON-COMPETING CONTINUATION	$418,031
2019	2019	SCINTILLON INSTITUTE,THE	6868 NANCY RIDGE DR	SAN DIEGO	CA	92121	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	8/29/2019	SUPPLEMENT FOR EXPANSION	$114,660
														Subtotal = $532,691

Issue Date FY: 2018 ( Subtotal = $418,031 )
2018	2018	SCINTILLON INSTITUTE,THE	6868 NANCY RIDGE DR	SAN DIEGO	CA	92121	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	6/28/2018	NON-COMPETING CONTINUATION	$418,031
														Subtotal = $418,031

Issue Date FY: 2017 ( Subtotal = $418,029 )
2017	2017	SCINTILLON INSTITUTE,THE	6868 NANCY RIDGE DR	SAN DIEGO	CA	92121	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	4	7/24/2017	NON-COMPETING CONTINUATION	$418,031
2017	2016	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	2	4/17/2017	NON-COMPETING CONTINUATION	-$73,598
2017	2016	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	3/8/2017	NON-COMPETING CONTINUATION	-$344,562
2017	2016	SCINTILLON INSTITUTE,THE	6868 NANCY RIDGE DR	SAN DIEGO	CA	92121	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	3	4/17/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$73,598
2017	2016	SCINTILLON INSTITUTE,THE	6404 NANCY RIDGE DR	SAN DIEGO	CA	92121	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	3/9/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$344,560
														Subtotal = $418,029

Issue Date FY: 2016 ( Subtotal = $421,094 )
2016	2016	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	7/19/2016	NON-COMPETING CONTINUATION	$421,094
														Subtotal = $421,094

Issue Date FY: 2015 ( Subtotal = $414,531 )
2015	2015	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/18/2015	NEW	$414,531
														Subtotal = $414,531

Grand Total All Awards = $2,204,376

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Peptidergic modulation of thermoregulation and energy expenditure

Award Number: R01NS094800

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/30/2015

PERIOD OF PERFORMANCE END DATE: 02/28/2022

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