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Determinants of sparse activity in neocortex

Award Number: R01NS123711
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: 02/15/2022
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Determinants of sparse activity in neocortex - ABSTRACT Synaptic plasticity in neocortical neurons is intimately tied to learning and memory. Decades of research in acute brain slices have characterized the patterns of spike timing required to evoke synaptic change in minute detail, but it remains unknown whether these conditions occur and are sufficient to drive synaptic plasticity in the living brain. Indeed, in vivo recordings indicate that neocortical neurons live in an environment of profound inhibition that lowers overall firing rates and prevents plasticity. How then do cortical neurons escape this inhibition to encounter appropriate conditions for plasticity during learning? New evidence suggests that parvalbumin (PV) GABAergic neurons may play a dominant role in regulating cortical activity and controlling network rewiring, particularly at the early stages of learning. Using a multiwhisker stimulus coupled to a water reward, we have developed a paradigm for sensory association learning that drives rapid changes in excitatory synaptic strength in mouse barrel cortex. Importantly, our new data indicate that PV output to neocortical pyramidal neurons is markedly suppressed at the earliest stages of sensory training. Our experiments will integrate in vivo and acute brain slice recordings to test the hypothesis that PV neurons are a dominant regulator of sensory- evoked activity in mouse barrel cortex. We propose that reward-related acetylcholine release indirectly suppresses PV neural firing to depress PV output and increase sensory-evoked activity during learning. Our experiments will identify mechanisms for cortical disinhibition that facilitate experience-dependent synaptic plasticity in sensory cortex.


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 = $455,632 )
2025	2025	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	12/14/2024	NON-COMPETING CONTINUATION	$455,632
														Subtotal = $455,632

Issue Date FY: 2024 ( Subtotal = $492,287 )
2024	2024	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	5/10/2024	NON-COMPETING CONTINUATION	$35,524
2024	2024	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	11/10/2023	NON-COMPETING CONTINUATION	$456,763
														Subtotal = $492,287

Issue Date FY: 2023 ( Subtotal = $508,733 )
2023	2023	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	12/5/2022	NON-COMPETING CONTINUATION	$457,861
2023	2023	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	1/31/2023	NON-COMPETING CONTINUATION	$50,872
														Subtotal = $508,733

Issue Date FY: 2022 ( Subtotal = $543,117 )
2022	2022	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	1/31/2022	NEW	$543,117
														Subtotal = $543,117

Grand Total All Awards = $1,999,769

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Determinants of sparse activity in neocortex

Award Number: R01NS123711

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: 02/15/2022

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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