# Neural circuit mechanisms underlying cognitive control of sensory-guided behavior

> **NIH NIH R01** · RUTGERS, THE STATE UNIV OF N.J. · 2020 · $339,063

## Abstract

SUMMARY
Response inhibition, the ability to inhibit actions in the appropriate contexts, is important for the cognitive
control of behavior and its dysfunction has been implicated in numerous neurological disorders. This proposal
aims to understand corticostriatal signaling underlying response inhibition in mice during performance and
learning of a whisker-based tactile discrimination task. A major goal is to address the gap in knowledge that
exists for the role of primary somatosensory cortex (S1) in response inhibition. Based on its prominent
projections to striatum and increasingly appreciated sensorimotor functionality, S1 is an overlooked candidate
for brain stimulation in behavioral control that could have therapeutic advantages compared to frontal brain
areas. The proposed experiments first aim to establish a causal relationship between cortical input from S1
and behavioral task performance. The hypothesis is that signaling from S1 to dorsal striatum (DStr), via its
massive axonal projection, is necessary and sufficient to drive behavioral responses and response inhibition in
the appropriate behavioral context. We will test this hypothesis by expressing optogenetic actuators and
silencers (ChR2, ArchT) in S1 and manipulating axonal activity in DStr during task performance. The results
will establish the causal influence of S1 on sensory-guided behavior. The next series of experiments will
investigate the cellular basis of task-related activity in S1 using chronic in vivo two-photon imaging and
electrophysiology. Chronic imaging of genetically encoded calcium indicators will allow for imaging of deep
layer striatal projection neurons in S1 to determine the behavioral selectivity of S1-DStr populations. The
hypothesis is that subpopulations of S1-DStr neurons encode response activation and inhibition, respectively.
The timing of behavior-related neuronal activity will be resolved using targeted electrophysiological recordings.
The final series of experiments will determine the emergence of cellular behavioral selectivity by tracking
activity changes in S1 using chronic two-photon imaging. Experiments will be performed both through initial
learning and stimulus reversal to dissociate stimulus and response. Our experimental approach will provide
critical information about the capacity of S1-DStr projections for eliciting response inhibition, which will have
implications for improved treatment of neurological disorders involving deficits in cognitive/behavioral control.

## Key facts

- **NIH application ID:** 9914354
- **Project number:** 5R01NS094450-05
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** David J Margolis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $339,063
- **Award type:** 5
- **Project period:** 2016-05-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9914354

## Citation

> US National Institutes of Health, RePORTER application 9914354, Neural circuit mechanisms underlying cognitive control of sensory-guided behavior (5R01NS094450-05). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9914354. Licensed CC0.

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