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Chronic nicotine and synaptic transmission in brainstem respiratory neurons

Award Number: R01HD071302
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/10/2012
PERIOD OF PERFORMANCE END DATE: 04/30/2024

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Chronic nicotine and synaptic transmission in brainstem respiratory neurons - Despite a growing body of evidence showing that in utero nicotine exposure leads to aberrant development of brainstem neurons involved in the maintenance of key homeostatic functions such as breathing, the consumption of nicotine via smokeless nicotine delivery devices (e.g., e-cigarettes, water pipes, nicotine patches or gum) more than doubled between 2008-2012. A particular concern is raised by recent studies showing that 30% of pregnant smokers were advised to use nicotine patches or gum by their physician. To date, the majority of the data on nicotine exposure and development of brainstem neurons has focused on how in utero exposure alters the brains of very young neonatal animals. As a result, we do not know if the changes observed with in utero exposure resolve or persist with maturation, or worsen if exposure continues after birth. The specific objective of this application is to test the hypothesis that prenatal and/or postnatal exposure to nicotine alters the structure and function of brainstem neurons that control the muscles of the tongue (hypoglossal motor neurons, XIIMNs), using an in vitro approach, as well as the breathing-related control of the tongue muscles, using an in vivo approach. The tongue muscles participate in breathing, swallowing, suckling and mastication, and therefore are critical for organismal homeostasis. A key focus is whether abnormal development of the tongue muscle motor system is worsened if nicotine exposure continues after birth, or if the alterations persist or are attenuated if exposure ends at weaning. Animals (rats) will be studied at key developmental time points, including the early neonatal period (postnatal day 1 (P1) - P5); the putative critical period for development of brainstem neurons (P10 - P12); the end of adolescence when brain maturation is largely complete (P50 – P60); and after sexual and social maturity (4 – 6 months). Specific Aims: We will use neuroanatomy, immunohistochemistry, patch clamp electrophysiology and in vivo plethysmography and EMG recordings to examine how prenatal and/or postnatal nicotine exposure alters: 1) the dendrite branching pattern and the expression of inhibitory (GABA, glycine) and excitatory (glutamate) neurotransmitter receptors on XIIMNs; 2) development of important neuron membrane properties (resting potential, voltage threshold for spike initiation, etc.), the cell's response to excitatory and inhibitory neurotransmitters; 3) development of the breathing pattern and the function of tongue muscles during normal, quiet breathing and when breathing is increased in response to an acute nicotine challenge or by increasing inspired carbon dioxide. The proposed experiments will result in a comprehensive understanding of how in utero and life-long nicotine exposure alters development of brainstem motoneurons that are critical for survival.


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: 2024 ( Subtotal = $0 )
2024	2022	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Child Health and Human Development Extramural Research	000	10	7/23/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $374,040 )
2022	2022	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Child Health and Human Development Extramural Research	000	10	5/25/2022	NON-COMPETING CONTINUATION	$374,040
														Subtotal = $374,040

Issue Date FY: 2021 ( Subtotal = $374,040 )
2021	2021	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Child Health and Human Development Extramural Research	000	9	5/5/2021	NON-COMPETING CONTINUATION	$374,040
														Subtotal = $374,040

Issue Date FY: 2020 ( Subtotal = $381,673 )
2020	2020	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Child Health and Human Development Extramural Research	000	8	4/17/2020	NON-COMPETING CONTINUATION	$381,673
														Subtotal = $381,673

Issue Date FY: 2019 ( Subtotal = $381,673 )
2019	2019	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Child Health and Human Development Extramural Research	000	7	4/22/2019	NON-COMPETING CONTINUATION	$381,673
														Subtotal = $381,673

Issue Date FY: 2018 ( Subtotal = $462,350 )
2018	2018	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Child Health and Human Development Extramural Research	001	6	7/12/2018	COMPETING CONTINUATION	$462,350
2018	2016	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Child Health and Human Development Extramural Research	000	5	6/19/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $462,350

Issue Date FY: 2016 ( Subtotal = $308,825 )
2016	2016	UNIVERSITY OF ARIZONA	POST OFFICE BOX 3308	TUCSON	AZ	85722		USA	Child Health and Human Development Extramural Research	000	5	5/4/2016	EXTENSION WITH OR WITHOUT FUNDS	$308,825
														Subtotal = $308,825

Issue Date FY: 2015 ( Subtotal = $304,145 )
2015	2015	UNIVERSITY OF ARIZONA	POST OFFICE BOX 3308	TUCSON	AZ	85722		USA	Child Health and Human Development Extramural Research	000	4	4/23/2015	NON-COMPETING CONTINUATION	$304,145
														Subtotal = $304,145

Issue Date FY: 2014 ( Subtotal = $303,210 )
2014	2014	UNIVERSITY OF ARIZONA	POST OFFICE BOX 3308	TUCSON	AZ	85722		USA	Child Health and Human Development Extramural Research	000	3	5/29/2014	NON-COMPETING CONTINUATION	$303,210
														Subtotal = $303,210

Issue Date FY: 2013 ( Subtotal = $296,036 )
2013	2013	UNIVERSITY OF ARIZONA	POST OFFICE BOX 3308	TUCSON	AZ	85722		USA	Child Health and Human Development Extramural Research	001	2	5/20/2013	NON-COMPETING CONTINUATION	$15,286
2013	2013	UNIVERSITY OF ARIZONA	POST OFFICE BOX 3308	TUCSON	AZ	85722		USA	Child Health and Human Development Extramural Research	000	2	5/10/2013	NON-COMPETING CONTINUATION	$280,750
														Subtotal = $296,036

Issue Date FY: 2012 ( Subtotal = $311,945 )
2012	2012	UNIVERSITY OF ARIZONA	POST OFFICE BOX 3308	TUCSON	AZ	85722		USA	Child Health and Human Development Extramural Research	000	1	7/10/2012	NEW	$311,945
														Subtotal = $311,945

Grand Total All Awards = $3,497,937

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Chronic nicotine and synaptic transmission in brainstem respiratory neurons

Award Number: R01HD071302

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/10/2012

PERIOD OF PERFORMANCE END DATE: 04/30/2024

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