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Cell Type-Specific Mechanisms of History-Dependent Perceptual Biases in Sensory Cortex

Award Number: R00NS129753
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: 08/15/2023
PERIOD OF PERFORMANCE END DATE: 07/31/2028

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Cell Type-Specific Mechanisms of History-Dependent Perceptual Biases in Sensory Cortex - PROJECT SUMMARY Sensory representations are influenced by an animal’s external context, internal state, past experiences, expectations, and future goals. Prior information – including the history of recent stimuli, actions and rewards – plays an important role in guiding ongoing behavior, and can modulate the neural code even at the level of primary sensory cortex. The involvement of sensory cortex in mediating history- dependent shifts in behavior, and the contributions of specific cell types to these effects are not well understood. Using a novel whisker-based behavioral paradigm, I have demonstrated that mice can flexibly and selectively enhance sensory processing of recently rewarded whisker stimuli based on history cues. Here, I propose experiments to uncover the cell type-specific mechanisms in for history-based modulation in primary somatosensory cortex (S1), and test for their causal role in behavior. In Aim 1 (K99), I will use behavioral modeling approaches to systematically quantify history-based perceptual biases during goal-directed behavior in mice. I will examine modulation of pyramidal (PYR) cell activity in S1 of behaving mice while tracking trial-by-trial behavioral shifts in sensory detection performance guided by recent history. I will then empirically test the necessity of S1 in mediating history effects on behavior using reversible inactivation techniques. Two cortical interneuron classes, namely VIP cells and NDNF cells, are widely theorized to play a role in selective enhancement of sensory processing in cortex, since they receive a wide range of glutamatergic and neuromodulatory inputs and boost sensory responses in PYR cells through local disinhibition. Both these cell types are activated in different active behavioral states and learning contexts. In Aim 2 (K99/R00), I will test the role of VIP and NDNF interneurons in gating history-related signals using 2p imaging to monitor their neural activity, and through targeted activation or inactivation of these cell types using optogenetic techniques. VIP and NDNF interneurons are both recruited by acetylcholine, a neuromodulator that is necessary for stimulus-specific enhancement of sensory processing in primates, and behavioral state-based modulation of sensory cortex in rodents. In Aim 3 (R00), I will test the role of basal forebrain cholinergic projections in conveying history-related signals to S1. I will perform two-photon imaging of cholinergic terminals in S1 and use selective optogenetic activation to test whether the locus of prioritized processing on the whiskers can be artificially shifted in behaving mice. Together, the proposed studies will provide new insights into the local cortical circuits that facilitate prioritized processing of behaviorally relevant stimuli in sensory maps.


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: 2026 ( Subtotal = $224,100 )
2026	2026	THE REGENTS OF THE UNIVERSITY OF CALIFORNIA	900 UNIVERSITY AVE	RIVERSIDE	CA	92521	RIVERSIDE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	9/15/2026	NON-COMPETING CONTINUATION	$224,100
2026	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	1/28/2026	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $224,100

Issue Date FY: 2025 ( Subtotal = $224,100 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	8/20/2025	EXTENSION WITH OR WITHOUT FUNDS	$224,100
														Subtotal = $224,100

Grand Total All Awards = $448,200

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Cell Type-Specific Mechanisms of History-Dependent Perceptual Biases in Sensory Cortex

Award Number: R00NS129753

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: 08/15/2023

PERIOD OF PERFORMANCE END DATE: 07/31/2028

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