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Defining functional circuits between CN molecular subpopulations and the cerebral cortex

Award Number: R37MH085726
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/21/2019
PERIOD OF PERFORMANCE END DATE: 11/30/2024

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Defining functional circuits between CN molecular subpopulations and the cerebral cortex - Recent work has provided evidence for functional connections between the cerebellum and cerebral cortex, with the hemispheres and central zone of the vermis housing the main cerebro-cerebellar circuits. Cerebellar neuropathologies have been detected in cognitive disorders including autism spectrum disorder (ASD), schizophrenia and dementias, and modulation of Purkinje neurons in one lobule in the right lateral cerebellum results in altered social and cognitive behaviors. The excitatory neurons of the cerebellar nuclei (eCN) are the output neurons of the cerebellum that interconnect with the cerebral cortex via the pons and thalamus, but their development, electrophysiology and molecular genetics are poorly understood. In particular, functional relationships between the cerebellar nuclei and cerebral cortex have not been demonstrated. In order to understand how the cerebellum functions and modulates the activity of the cerebral cortex, it is necessary to define the molecular diversity of the eCN, understand how eCN subpopulations (subP) develop, map their circuitry and relate cerebro-cerebellar functions to specific eCN subP. A major problem for such studies is a lack of genetic tools for specifically marking and modulating eCN. This project will define molecular subP of the eCN and determine how and when the subP form during normal development and in developmental mutants in which a subset of eCN are lost (En1/2 mutants) using single cell RNA sequencing (scRNA-seq). Mouse lines will then be developed to manipulate eCN subP and applied to mapping the synaptic partners of subP of eCN and to optogenetics to inhibit/activate specific eCN. Electrophysiology and cognitive/social behavior assays will be used to determine the functional interactions between specific subP of the eCN and regions of the cerebral cortex. This project represents the first definition of the molecular subP of the cerebellar nuclei and determination of their functional impact on cerebral cortex functions. RELEVANCE (See instructions): The cerebellum, in addition to the cerebral cortex, is involved in cognitive and social disorders including autism and schizophrenia, however little is know of the neural circuits that connect the two brain structures. We will map how distinct subpopulations of neurons in the cerebellum project to the cerebral cortex during development and determine how they influence cerebro-cerebellar functions. Our results will provide insights into how cerebro-cerebellar circuits function and might be therapeutically modified in diseases.


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	2023	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Mental Health Research Grants	000	15	3/31/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $684,560 )
2023	2023	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Mental Health Research Grants	001	15	3/6/2023	NON-COMPETING CONTINUATION	$68,456
2023	2023	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Mental Health Research Grants	000	15	12/20/2022	NON-COMPETING CONTINUATION	$616,104
														Subtotal = $684,560

Issue Date FY: 2022 ( Subtotal = $684,560 )
2022	2022	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Mental Health Research Grants	001	14	6/26/2022	NON-COMPETING CONTINUATION	$68,456
2022	2022	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Mental Health Research Grants	000	14	11/18/2021	NON-COMPETING CONTINUATION	$616,104
														Subtotal = $684,560

Issue Date FY: 2021 ( Subtotal = $684,560 )
2021	2021	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Mental Health Research Grants	001	13	4/21/2021	NON-COMPETING CONTINUATION	$68,456
2021	2021	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Mental Health Research Grants	000	13	11/27/2020	NON-COMPETING CONTINUATION	$616,104
														Subtotal = $684,560

Issue Date FY: 2020 ( Subtotal = $684,560 )
2020	2020	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Mental Health Research Grants	000	12	11/27/2019	NON-COMPETING CONTINUATION	$616,104
2020	2020	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Mental Health Research Grants	001	12	3/11/2020	NON-COMPETING CONTINUATION	$68,456
														Subtotal = $684,560

Issue Date FY: 2019 ( Subtotal = $704,460 )
2019	2019	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Mental Health Research Grants	001	11	2/5/2019	EXTENSION WITH OR WITHOUT FUNDS	$0
2019	2019	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Mental Health Research Grants	000	11	1/21/2019	EXTENSION WITH OR WITHOUT FUNDS	$704,460
2019	2018	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Mental Health Research Grants	002	10	4/25/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $704,460

Issue Date FY: 2018 ( Subtotal = $639,375 )
2018	2018	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Mental Health Research Grants	000	10	12/5/2017	NON-COMPETING CONTINUATION	$575,439
2018	2018	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Mental Health Research Grants	001	10	6/15/2018	NON-COMPETING CONTINUATION	$63,936
														Subtotal = $639,375

Issue Date FY: 2017 ( Subtotal = $639,375 )
2017	2017	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Mental Health Research Grants	000	9	12/20/2016	NON-COMPETING CONTINUATION	$575,439
2017	2017	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Mental Health Research Grants	001	9	6/6/2017	NON-COMPETING CONTINUATION	$63,936
														Subtotal = $639,375

Issue Date FY: 2016 ( Subtotal = $639,375 )
2016	2016	SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Mental Health Research Grants	000	8	12/30/2015	NON-COMPETING CONTINUATION	$575,439
2016	2016	SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Mental Health Research Grants	001	8	3/15/2016	NON-COMPETING CONTINUATION	$63,936
														Subtotal = $639,375

Issue Date FY: 2015 ( Subtotal = $639,375 )
2015	2015	SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Mental Health Research Grants	000	7	12/17/2014	NON-COMPETING CONTINUATION	$575,439
2015	2015	SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Mental Health Research Grants	001	7	2/20/2015	NON-COMPETING CONTINUATION	$63,936
														Subtotal = $639,375

Issue Date FY: 2014 ( Subtotal = $657,501 )
2014	2014	SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Mental Health Research Grants	000	6	12/1/2013	COMPETING CONTINUATION	$657,501
														Subtotal = $657,501

Grand Total All Awards = $6,657,701

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Defining functional circuits between CN molecular subpopulations and the cerebral cortex

Award Number: R37MH085726

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/21/2019

PERIOD OF PERFORMANCE END DATE: 11/30/2024

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