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Circuits for deviance detection in V1

Award Number: R01EY033950
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 10/03/2024
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Circuits for deviance detection in V1 - PROJECT SUMMARY Brain responses to stimuli are not static over time but are dynamically modulated by the context of concurrent and preceding stimuli. This supports the rapid detection of behaviorally relevant information which may be key for survival in complex environments. In the visual system, neural activity as early as primary visual cortex (V1) is increased to stimuli that deviate from contextual patterns, a phenomenon termed “deviance detection.” In human EEG recordings, this deviance detection is reflected in the “mismatch negativity”, an early scalp potential elicited by rare stimuli in, for example, an “oddball” sequence. Visual mismatch negativity, and likely deviance detection, is altered in many neurological and psychiatric disorders, indexing fundamental visual processing deficits that may undermine how affected individuals relate to their world. Despite this basic and clinical significance, the neural circuitry for generating deviance detection is unknown. Our past work has utilized mice to address this question at a basic level, given the powerful set of genetic and optical tools available in this animal. We identified robust deviance detection in mouse V1, particularly in pyramidal neurons (PYRs) in superficial cortical layers (layer 2/3). We then showed that V1 deviance detection is dependent on i) local GABAergic interneurons and ii) top-down inputs from higher cortical areas (anterior cingulate; ACa). Exactly how these circuit elements interact to modulate V1 activity in context, producing deviance detection to novel stimuli, is unclear. The current project will build these preliminary insights to test a detailed circuit hypothesis of how deviance detection responses emerge in V1 in layer 2/3. Specifically, we propose that top-down input to V1 (from ACa) engages a mutually inhibitory interneuron circuit, involving namely vasoactive intestinal peptide- (VIP) and somatostatin- (SST) neurons. This serves to transiently modulate the excitability of subsets of PYRs dependent on their feature selectivity, attenuating responses to redundant stimuli and augmenting responses to deviant stimuli. To test this hypothesis, we will present visual “oddball” and control sequences to awake mice (which allows us to parse true deviance detection from the absence of simple neural adaption). We will employ two- photon calcium imaging and spatiotemporally precise optogenetic interventions (one and two-photon) to record and manipulate cell-type specific activity dynamics in V1. In aim 1, we will optically probe PYR excitability with single cell resolution during specific phases of the oddball paradigm, assessing PYR responses relative to their feature selectivity. Next, we will optically suppress SST and VIPs in V1 (aim 2) and then top-down ACa inputs to V1 (aim 3) at specific phases of the oddball paradigm while recording PYRs, SSTs, and VIPs to precisely test predictions of our circuit hypothesis. This focused, technologically advanced approach, applied during a passive and highly translatable sensory stimulation paradigm, will provide fundamental insights which could transform how basic visual processing and central visual circuitry is studied and understood in health and disease.


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 = $411,533 )
2025	2025	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	140 OLD ORANGEBURG RD BLDG 35	ORANGEBURG	NY	10962	ROCKLAND	USA	Vision Research	004	5	8/25/2025	NON-COMPETING CONTINUATION	$411,533
2025	2024	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	140 OLD ORANGEBURG RD BLDG 35	ORANGEBURG	NY	10962	ROCKLAND	USA	Vision Research	001	4	2/14/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$392,356
2025	2024	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Vision Research	000	3	2/14/2025	NON-COMPETING CONTINUATION	-$392,356
2025	2024	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	140 OLD ORANGEBURG RD BLDG 35	ORANGEBURG	NY	10962	ROCKLAND	USA	Vision Research	003	4	5/13/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$69,175
2025	2023	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Vision Research	002	2	5/13/2025	NON-COMPETING CONTINUATION	-$69,175
														Subtotal = $411,533

Issue Date FY: 2024 ( Subtotal = $392,356 )
2024	2024	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Vision Research	000	3	7/19/2024	NON-COMPETING CONTINUATION	$392,356
														Subtotal = $392,356

Issue Date FY: 2023 ( Subtotal = $381,156 )
2023	2023	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Vision Research	000	2	7/12/2023	NON-COMPETING CONTINUATION	$381,156
														Subtotal = $381,156

Issue Date FY: 2022 ( Subtotal = $372,235 )
2022	2022	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.	58 EDGEWOOD AVE NE 3RD FL	ATLANTA	GA	30303	FULTON	USA	Vision Research	000	1	9/20/2022	NEW	$372,235
														Subtotal = $372,235

Grand Total All Awards = $1,557,280

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Circuits for deviance detection in V1

Award Number: R01EY033950

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 10/03/2024

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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