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Flexible normalization in ferret V1: computational modeling and 2-photon imaging

Award Number: R01NS123842
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: 08/01/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Flexible normalization in ferret V1: computational modeling and 2-photon imaging - ABSTRACT The remarkable efficiency of human perception derives from the fact that we do not process each stimulus as a novel event. Instead, past experiences and scene context inform internal, working models of the world that allow us to generate predictions for our physical environment. A leading theory suggests that perceptual predictions are accomplished via flexible normalization: local inhibitory neuronal populations are regulated by long-range connections so that responses are suppressed when they do not provide helpful information about object boundaries. However, the precise neural mechanisms by which the healthy human brain accomplishes this flexible normalization are not known. In order to understand exactly how neural population responses are suppressed or enhanced in response to different scene contexts, we will perform 2-photon imaging in ferret primary visual cortex (V1) to quantify the responses of excitatory and inhibitory neural populations in superficial layers of cortex during several different visual stimulus paradigms. The ferret model is chosen because the imaging techniques necessary to quantify inhibitory neuronal responses are not yet well established in primate models, and while our current knowledge about neural morphology and connections has been derived from mouse models, mouse visual cortex lacks the “columnar organization” (spatial grouping of neurons with similar response properties) that is a hallmark of primate visual cortex and is present in ferrets. Thus, the ferret model is well-positioned to bridge the gap between mouse models and primate models. First, in order to understand neuronal behaviors in the absence of contextual modulation, we will characterize interactions within a single hypercolumn to small, simple stimuli (sinusoidally modulated luminance gratings) at a range of orientations and contrasts. We hypothesize that parvalbumin-containing (PV+) inhibitory interneurons will demonstrate the sharpest orientation tuning, followed by somatostatin-containing (SOM+) and serotonin-positive (5HTR+) populations. Next. using a Cross Orientation Suppression paradigm, we will test the hypothesis that that SOM+ responses track the overall contrast energy in the stimulus, while PV+ populations reflect suppression of individual grating component representations. Additional experiments with naturalistic textures will test whether these behaviors generalize to stimuli with a broad range of contrasts, orientations, and spatial frequencies. Finally, we will use classical Orientation-Dependent Surround Suppression and Collinear Facilitation paradigms to study how the local inhibitory pool responds to scene context. We hypothesize that the responses of local 5HTR+ neurons will reflect the surrounding stimuli rather than the center stimuli. Together, these experiments will constrain an open-source computational model articulated at the level of the single neuron that will constrain hypotheses about how human perceptual behaviors are linked to specific neuronal populations; this model will be valuable for understanding how perceptual aberrations associated with psychosis might be mapped to the function of specific neuronal subpopulations.


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 = $389,631 )
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	6/30/2025	NON-COMPETING CONTINUATION	$389,631
2025	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	3/18/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $389,631

Issue Date FY: 2024 ( Subtotal = $412,091 )
2024	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	7/26/2024	NON-COMPETING CONTINUATION	$412,091
														Subtotal = $412,091

Issue Date FY: 2023 ( Subtotal = $457,879 )
2023	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	7/3/2023	NON-COMPETING CONTINUATION	$457,879
														Subtotal = $457,879

Issue Date FY: 2022 ( Subtotal = $457,879 )
2022	2022	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	7/7/2022	NON-COMPETING CONTINUATION	$457,879
														Subtotal = $457,879

Issue Date FY: 2021 ( Subtotal = $477,754 )
2021	2021	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	7/28/2021	NEW	$477,754
														Subtotal = $477,754

Grand Total All Awards = $2,195,234

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Flexible normalization in ferret V1: computational modeling and 2-photon imaging

Award Number: R01NS123842

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: 08/01/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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