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Synaptic and dendritic physiology in the prefrontal cortex

Award Number: R01MH085974
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/06/2010
PERIOD OF PERFORMANCE END DATE: 11/30/2024

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Synaptic and dendritic physiology in the prefrontal cortex - PROJECT SUMMARY Interactions between the thalamus and prefrontal cortex (PFC) are important for cognitive function in animals ranging from rodents to primates. The importance of these long-range networks is highlighted by multiple neuropsychiatric diseases, including schizophrenia and ADHD. However, most of what we know about thalamo-cortical circuits comes from sensory systems, where primary thalamic inputs arrive in layer 4 (L4). In contrast, the mouse PFC is an agranular area that lacks L4, and instead receives higher-order thalamic inputs directly to superficial layers. We recently discovered that the PFC makes reciprocal connections with both the mediodorsal (MD) and ventromedial (VM) thalamus. These thalamic nuclei support distinct behaviors, but the cellular, synaptic and circuit mechanisms for their interactions with PFC are poorly understood. We found MD strongly drives layer 2/3 (L2/3) pyramidal cells, whereas VM inputs contact the dendrites of a subset of L5 pyramidal cells. Interestingly, both inputs also robustly engage inhibitory networks to drive local inhibition mediated by GABAergic interneurons. The goal of this proposal is to assess how thalamic inputs engage different populations of superficial interneurons to mediate inhibition in the PFC. In Specific Aim 1, we use optogenetics and electrophysiology to study how thalamic inputs drive multiple classes of interneurons in superficial layers. Our preliminary data suggests that MD and VM engage complementary populations of interneurons located in different sub-layers. In Specific Aim 2, we then use conditional optogenetics to study how these interneurons contact excitatory and inhibitory cells within and across layers. Our preliminary data indicate that the interneurons contacted by MD and VM participate in distinct inhibitory and disinhibitory circuits across multiple layers. Lastly, in Specific Aim 3, we combine 1-photon optogenetics with 2-photon microscopy to study how specific populations of interneurons mediate the suppression of dendritic Ca2+ spikes. Our preliminary data reveal that a sub-population of superficial interneurons mediates robust feed-forward inhibition in the dendrites. Together, the results from our experiments will answer fundamental questions about the organization of thalamo-cortical circuits and interneurons in the PFC. They will also help identify potential therapeutic targets for the many neuropsychiatric disorders that arise from disrupted circuitry within the PFC.


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 = $506,300 )
2024	2024	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	000	15	12/6/2023	NON-COMPETING CONTINUATION	$455,670
2024	2024	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	001	15	8/19/2024	NON-COMPETING CONTINUATION	$50,630
														Subtotal = $506,300

Issue Date FY: 2023 ( Subtotal = $506,300 )
2023	2023	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	000	14	3/10/2023	NON-COMPETING CONTINUATION	$506,300
														Subtotal = $506,300

Issue Date FY: 2022 ( Subtotal = $506,300 )
2022	2022	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	001	13	5/11/2022	NON-COMPETING CONTINUATION	$50,630
2022	2022	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	000	13	11/26/2021	NON-COMPETING CONTINUATION	$455,670
														Subtotal = $506,300

Issue Date FY: 2021 ( Subtotal = $506,300 )
2021	2021	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	001	12	4/7/2021	NON-COMPETING CONTINUATION	$50,630
2021	2021	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	000	12	12/11/2020	NON-COMPETING CONTINUATION	$455,670
														Subtotal = $506,300

Issue Date FY: 2020 ( Subtotal = $532,947 )
2020	2020	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	003	11	8/3/2020	COMPETING CONTINUATION	$1,466
2020	2020	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	001	11	3/11/2020	COMPETING CONTINUATION	$53,295
2020	2020	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	000	11	11/28/2019	COMPETING CONTINUATION	$479,652
2020	2019	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	002	10	8/3/2020	NON-COMPETING CONTINUATION	-$1,466
														Subtotal = $532,947

Issue Date FY: 2019 ( Subtotal = $387,723 )
2019	2019	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	000	10	12/7/2018	NON-COMPETING CONTINUATION	$387,723
														Subtotal = $387,723

Issue Date FY: 2018 ( Subtotal = $387,971 )
2018	2018	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	001	9	6/20/2018	NON-COMPETING CONTINUATION	$38,798
2018	2018	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	000	9	11/15/2017	NON-COMPETING CONTINUATION	$349,173
														Subtotal = $387,971

Issue Date FY: 2017 ( Subtotal = $388,212 )
2017	2017	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	000	8	2/7/2017	NON-COMPETING CONTINUATION	$349,390
2017	2017	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	001	8	5/23/2017	NON-COMPETING CONTINUATION	$38,822
2017	2015	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	003	6	6/29/2017	COMPETING CONTINUATION	$1,447
2017	2014	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	002	5	6/29/2017	NON-COMPETING CONTINUATION	-$1,447
														Subtotal = $388,212

Issue Date FY: 2016 ( Subtotal = $388,447 )
2016	2016	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Mental Health Research Grants	000	7	11/21/2015	NON-COMPETING CONTINUATION	$349,602
2016	2016	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Mental Health Research Grants	001	7	12/29/2015	NON-COMPETING CONTINUATION	$0
2016	2016	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Mental Health Research Grants	002	7	3/12/2016	NON-COMPETING CONTINUATION	$38,845
														Subtotal = $388,447

Issue Date FY: 2015 ( Subtotal = $388,674 )
2015	2015	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Mental Health Research Grants	000	6	12/25/2014	COMPETING CONTINUATION	$388,674
														Subtotal = $388,674

Issue Date FY: 2014 ( Subtotal = $373,736 )
2014	2014	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Mental Health Research Grants	001	5	5/7/2014	NON-COMPETING CONTINUATION	$37,374
2014	2014	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Mental Health Research Grants	000	5	12/16/2013	NON-COMPETING CONTINUATION	$336,362
														Subtotal = $373,736

Issue Date FY: 2013 ( Subtotal = $359,071 )
2013	2013	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Mental Health Research Grants	001	4	6/10/2013	NON-COMPETING CONTINUATION	$22,442
2013	2013	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Mental Health Research Grants	000	4	12/10/2012	NON-COMPETING CONTINUATION	$336,629
														Subtotal = $359,071

Issue Date FY: 2012 ( Subtotal = $374,329 )
2012	2012	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Mental Health Research Grants	000	3	12/20/2011	NON-COMPETING CONTINUATION	$336,896
2012	2012	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Mental Health Research Grants	001	3	3/8/2012	NON-COMPETING CONTINUATION	$37,433
														Subtotal = $374,329

Issue Date FY: 2011 ( Subtotal = $374,626 )
2011	2011	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Mental Health Research Grants	000	2	12/14/2010	NON-COMPETING CONTINUATION	$340,569
2011	2011	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Mental Health Research Grants	001	2	5/27/2011	NON-COMPETING CONTINUATION	$34,057
														Subtotal = $374,626

Issue Date FY: 2010 ( Subtotal = $378,710 )
2010	2010	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Mental Health Research Grants	000	1	1/5/2010	NEW	$378,710
														Subtotal = $378,710

Grand Total All Awards = $6,359,646

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Synaptic and dendritic physiology in the prefrontal cortex

Award Number: R01MH085974

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/06/2010

PERIOD OF PERFORMANCE END DATE: 11/30/2024

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