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Synaptic Coding in the Cerebellar Corticonuclear Circuit

Award Number: R35NS116854
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: 05/01/2020
PERIOD OF PERFORMANCE END DATE: 04/30/2028

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Synaptic Coding in the Cerebellar Corticonuclear Circuit - Project Summary/Abstract (unchanged from parent proposal) Premotor neurons of the cerebellar nuclei (CbN) are spontaneously active neurons that integrate excitatory and inhibitory input, largely from mossy fibers and Purkinje neurons, to generate the output of the cerebellum. The cerebellum facilitates coordinated movement and corrects errors in real time, and also changes to learn new motor patterns over time. These observations raise the question of how synaptic input modulates intrinsic firing in a manner that permits premotor CbN neurons to identify deviations from predicted sensory input and encode appropriate corrective outputs. We are studying the biophysical and synaptic mechanisms that constrain and define patterns of CbN cell firing in response to physiological patterns of synaptic input in vitro and expected or unexpected sensory input during motor behaviors in vivo. Recent work suggests that the degree of inhibitory synchrony from convergent Purkinje cells may dictate cerebellar output in mice in a condition-dependent manner. We will therefore study cerebellar physiology and behavior in mice and in larval zebrafish, to provide a comparative approach, both in vitro and in vivo. Purkinje and CbN cell firing patterns will be monitored both during well-learned, predictable motor behaviors, during unpredicted sensory inputs, and during motor learning such as habituation and associative conditioning. The observations will be related to synaptic studies of the interaction of excitatory with inhibitory inputs, convergence and connectivity, and short- term and long-term plasticity. Such linking of the biophysical and behavioral levels will help explain the mechanisms by which the cerebellar circuit produces adaptive responses to deviations from predictions, thereby facilitating well-executed movement.


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 = $838,019 )
2025	2025	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	4/9/2025	NON-COMPETING CONTINUATION	$640,827
2025	2025	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	8/14/2025	SUPPLEMENT FOR EXPANSION	$197,192
														Subtotal = $838,019

Issue Date FY: 2024 ( Subtotal = $630,961 )
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	5	8/26/2024	NON-COMPETING CONTINUATION	$0
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	3/8/2024	NON-COMPETING CONTINUATION	$585,426
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	4/25/2024	NON-COMPETING CONTINUATION	$45,535
														Subtotal = $630,961

Issue Date FY: 2023 ( Subtotal = $819,812 )
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	5/1/2023	NON-COMPETING CONTINUATION	$659,812
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	8/14/2023	SUPPLEMENT FOR EXPANSION	$160,000
														Subtotal = $819,812

Issue Date FY: 2022 ( Subtotal = $662,117 )
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	4/21/2022	NON-COMPETING CONTINUATION	$662,117
														Subtotal = $662,117

Issue Date FY: 2021 ( Subtotal = $670,262 )
2021	2021	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	4/1/2021	NON-COMPETING CONTINUATION	$670,262
														Subtotal = $670,262

Issue Date FY: 2020 ( Subtotal = $628,591 )
2020	2020	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	4/21/2020	NEW	$628,591
														Subtotal = $628,591

Grand Total All Awards = $4,249,762

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Synaptic Coding in the Cerebellar Corticonuclear Circuit

Award Number: R35NS116854

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: 05/01/2020

PERIOD OF PERFORMANCE END DATE: 04/30/2028

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