Wednesday, August 20, 2025 8/20/2025

Coordination of M1 projection neuron subtypes by oscillations

Award Number: R01NS123396
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: 04/01/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Coordination of M1 projection neuron subtypes by oscillations - PROJECT SUMMARY/ABSTRACT Motor acts such as reaching often rely upon the primary motor cortex (M1) for their execution. Oscillatory activities in M1 accompany motor actions, with the dominant electroencephalographic correlate of those actions being event-related desynchronization (ERD), a loss of low frequency power during movement onsets. Intracerebral recordings in humans, monkeys, and rodents have found that ERD co-occurs with movement associated gamma oscillations in M1. Gamma has received increased attention as a therapeutic target because it is altered in several movement disorders and affected by transcranial stimulation. However, the microcircuitry and function of gamma oscillations in M1 are not well studied. Given the abundance of specialized projection neurons in M1, it is crucial to understand how they are coordinated by gamma in normal subjects. In other cortical circuits, gamma oscillations depend on the interaction between principal cells (PNs) and fast-spiking interneurons (FSIs). In M1, projection-specific PN subtypes differ in their connectivity with FSIs, suggesting that they are differentially regulated by gamma. This project seeks to understand how gamma oscillations during reaching orchestrate three major classes of PNs in M1: pyramidal tract, corticostriatal, and corticothalamic. In Aim 1, local field potentials and single unit activity in M1 are recorded during a skilled reaching task in rats. Extracellular spike waveform characteristics will be used to identify FSIs, while PNs will be classified with antidromic stimulation. Paw kinematics will be tracked to measure reaching. For each PN subtype, we will characterize entrainment to gamma, coordination with FSIs, and reaching correlates. Aim 2 dissects the circuit mechanisms underlying any projection-specific differences in gamma entrainment. For each pair of PN subtypes, one will be made to selectively express the excitatory opsin ChroME, while the other will be labeled with GFP. In M1 brain slices, whole-cell patch clamp recordings will be made from both populations during gamma induced by optogenetic ramp stimuli. This will reveal the ability for the opsin-bearing population to induce local gamma, and how sensitive the GFP population is to it. Voltage clamp recordings will reveal the relative contributions of EPSCs and IPSCs to these rhythms, further illuminating circuit mechanisms. Lastly, Aim 3 assesses the behavioral importance of gamma entrainment. During the reaching task closed-loop optogenetic modulation of each of the PN subtypes will be delivered to bias their spiking either in- or out-of-phase with ongoing M1 gamma. The effect this has on gamma amplitude, behavioral performance, and the unstimulated projection PNs, will be determined. Altogether, these aims offer a comprehensive characterization of how M1 gamma coordinates the output microcircuitry, clarifies its physiology, and tests its behavioral relevance. Those insights are necessary for deepening our understanding of oscillatory activities in M1 and motor disordes, and perfecting future therapies.


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 = $392,500 )
2025	2025	RUTGERS, THE STATE UNIVERSITY	123 WASHINGTON ST	NEWARK	NJ	07102	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	3/20/2025	NON-COMPETING CONTINUATION	$353,250
2025	2025	RUTGERS, THE STATE UNIVERSITY	123 WASHINGTON ST	NEWARK	NJ	07102	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	7/21/2025	NON-COMPETING CONTINUATION	$39,250
														Subtotal = $392,500

Issue Date FY: 2024 ( Subtotal = $380,725 )
2024	2024	RUTGERS, THE STATE UNIVERSITY	123 WASHINGTON ST	NEWARK	NJ	07102	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	006	3	4/12/2024	NON-COMPETING CONTINUATION	$27,475
2024	2024	RUTGERS, THE STATE UNIVERSITY	123 WASHINGTON ST	NEWARK	NJ	07102	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	005	3	3/11/2024	NON-COMPETING CONTINUATION	$353,250
2024	2023	RUTGERS, THE STATE UNIVERSITY	123 WASHINGTON ST	NEWARK	NJ	07102	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	2	2/23/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$50,190
2024	2023	RUTGERS, THE STATE UNIVERSITY	123 WASHINGTON ST	NEWARK	NJ	07102	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	2	2/21/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$392,500
2024	2023	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	2/8/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$392,500
2024	2022	RUTGERS, THE STATE UNIVERSITY	123 WASHINGTON ST	NEWARK	NJ	07102	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	2/5/2024	NEW	$0
2024	2022	RUTGERS, THE STATE UNIVERSITY	123 WASHINGTON ST	NEWARK	NJ	07102	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	1	2/23/2024	NEW	-$50,190
														Subtotal = $380,725

Issue Date FY: 2023 ( Subtotal = $392,500 )
2023	2023	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	4/7/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$392,500
														Subtotal = $392,500

Issue Date FY: 2022 ( Subtotal = $392,500 )
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	123 WASHINGTON ST STE 510	NEWARK	NJ	07102	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	4/29/2022	NEW	$0
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	123 WASHINGTON ST STE 510	NEWARK	NJ	07102	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	3/16/2022	NEW	$392,500
														Subtotal = $392,500

Grand Total All Awards = $1,558,225

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Coordination of M1 projection neuron subtypes by oscillations

Award Number: R01NS123396

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: 04/01/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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