Saturday, December 3, 2022 12/3/2022

Dense-Core Vesicle Circulation, Capture and Synaptic Neuropeptide Release

Award Number: R01NS032385
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

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Project Description Neuropeptides and neurotrophins are packaged in dense-core vesicles (DCVs) in the soma and released at synaptic terminals to control development, mood and numerous behaviors. Despite the importance of neuronal DCVs, little was known about how they are delivered to terminals and release their contents at synapses. Our GFP-based imaging studies combined with Drosophila genetics have revealed that control of synaptic peptide stores and exocytotic release do not operate as advertised in text books. First, instead of a one-way trip mediated by anterograde axonal transport, DCVs circulate in and out of synapses with capture occurring during both anterograde and retrograde transport. Moreover, contrary to long-held assumptions, capture limits the size of presynaptic neuropeptide pool. Furthermore, we have recently found that capture efficiency is directionally controlled by activity, neuron subtype and disease-related genes. Second, preliminary studies suggest that DCV transport appears to be adjusted for extensive innervation with many boutons (e.g. ~1000) and injury in the terminal. The latter effect is associated with intraterminal Ca2+ release, which may potentiate synaptic function to compensate for loss of boutons induced by injury. Third, a monoamine neuromodulator and intracellular cAMP evoke robust synaptic peptide release, with the latter displaying mechanistic differences from release evoked by action potentials. These results suggest that, in addition to conventional transmission evoked by electrical activity, synaptic peptide release is evoked by intracellular Ca2+ release and cAMP signaling. Here fluorescent protein imaging in Drosophila neurons addresses three questions posed by our prior work on this project: 1. What molecular mechanisms selectively control presynaptic DCV capture and neuropeptide release? 2. How is vesicle circulation regulated to support extensive, diverse and injured terminals? 3. What is the release mechanism and physiological impact of intracellular Ca2+ and/or cAMP signaling evoked by injury and neuromodulators? These studies will yield fundamental insights into the maintenance of terminals and the regulation of synaptic release of neuropeptides and neurotrophins. Furthermore, the proposal will show how these processes are affected by acute injury and disease-related genes.


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 = $811,125 )
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	26	8/26/2022	COMPETING CONTINUATION	$14,007
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	26	7/14/2022	COMPETING CONTINUATION	$797,118
2022	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	25	7/7/2022	NON-COMPETING CONTINUATION	$0


Issue Date FY: 2021 ( Subtotal = $540,865 )
2021	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	25	5/24/2021	NON-COMPETING CONTINUATION	$540,865


Issue Date FY: 2020 ( Subtotal = $542,813 )
2020	2020	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	24	5/8/2020	NON-COMPETING CONTINUATION	$542,813


Issue Date FY: 2019 ( Subtotal = $540,865 )
2019	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	23	5/6/2019	NON-COMPETING CONTINUATION	$540,865


Issue Date FY: 2018 ( Subtotal = $541,951 )
2018	2018	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	22	5/1/2018	NON-COMPETING CONTINUATION	$541,951


Issue Date FY: 2017 ( Subtotal = $550,825 )
2017	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	21	8/21/2017	COMPETING CONTINUATION	$83,953
2017	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	21	3/27/2017	COMPETING CONTINUATION	$550,825
2017	2016	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	20	8/21/2017	EXTENSION WITH OR WITHOUT FUNDS	-$83,953


Issue Date FY: 2016 ( Subtotal = $389,605 )
2016	2016	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	20	5/13/2016	EXTENSION WITH OR WITHOUT FUNDS	$389,605


Issue Date FY: 2015 ( Subtotal = $389,605 )
2015	2015	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	19	4/21/2015	NON-COMPETING CONTINUATION	$389,605


Issue Date FY: 2014 ( Subtotal = $385,709 )
2014	2014	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	18	4/14/2014	NON-COMPETING CONTINUATION	$385,709


Issue Date FY: 2013 ( Subtotal = $375,968 )
2013	2013	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	17	4/26/2013	NON-COMPETING CONTINUATION	$350,644
2013	2013	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	17	5/22/2013	NON-COMPETING CONTINUATION	$25,324


Issue Date FY: 2012 ( Subtotal = $402,480 )
2012	2012	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	16	5/18/2012	COMPETING CONTINUATION	$402,480


Issue Date FY: 2011 ( Subtotal = $417,421 )
2011	2011	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	15	7/11/2011	NON-COMPETING CONTINUATION	$26,562
2011	2011	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	15	4/15/2011	NON-COMPETING CONTINUATION	$390,859


Issue Date FY: 2010 ( Subtotal = $440,149 )
2010	2010	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	14	4/30/2010	NON-COMPETING CONTINUATION	$417,424
2010	2010	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	14	9/17/2010	SUPPLEMENT FOR EXPANSION	$22,725


Issue Date FY: 2009 ( Subtotal = $409,358 )
2009	2009	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	5/6/2009	NON-COMPETING CONTINUATION	$409,358


Issue Date FY: 2008 ( Subtotal = $421,312 )
2008	2008	UNIVERSITY OF PITTSBURGH	3017 CATHEDRAL OF LEARNING	PITTSBURGH	PA	15260	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	12	4/2/2008	COMPETING CONTINUATION	$421,312


Issue Date FY: 2007 ( Subtotal = $350,387 )
2007	2007	UNIVERSITY OF PITTSBURGH	FIFTH & BIGELOW BOULEVARD	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	5/10/2007	NON-COMPETING CONTINUATION	$350,387


Issue Date FY: 2006 ( Subtotal = $350,344 )
2006	2006	UNIVERSITY OF PITTSBURGH	FIFTH & BIGELOW BOULEVARD	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	5/19/2006	NON-COMPETING CONTINUATION	$350,344


Issue Date FY: 2005 ( Subtotal = $353,397 )
2005	2005	UNIVERSITY OF PITTSBURGH	FIFTH & BIGELOW BOULEVARD	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	5/19/2005	NON-COMPETING CONTINUATION	$353,397


Issue Date FY: 2004 ( Subtotal = $382,356 )
2004	2004	UNIVERSITY OF PITTSBURGH	FIFTH & BIGELOW BOULEVARD	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	8	8/16/2004	SUPPLEMENT FOR EXPANSION	$25,000
2004	2004	UNIVERSITY OF PITTSBURGH	FIFTH & BIGELOW BOULEVARD	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	5/20/2004	COMPETING CONTINUATION	$357,356


Issue Date FY: 2003 ( Subtotal = $321,778 )
2003	2003	UNIVERSITY OF PITTSBURGH	FIFTH & BIGELOW BOULEVARD	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7		NON-COMPETING CONTINUATION	$321,778


Issue Date FY: 2002 ( Subtotal = $312,918 )
2002	2002	UNIVERSITY OF PITTSBURGH	FIFTH & BIGELOW BOULEVARD	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biological Basis Research in the Neurosciences	000	6	12/28/2001	NON-COMPETING CONTINUATION	$312,918


Grand Total All Awards = $9,826,201

Sum of Action Amount is $9,826,201;

Grand Total = $9,826,201

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Dense-Core Vesicle Circulation, Capture and Synaptic Neuropeptide Release

Award Number: R01NS032385

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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