# Supplement to Communication between Networks: Context, Inhibition, and Neuromodulation

> **NIH NIH DP2** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $165,984

## Abstract

Project Summary
The brain is often bombarded by streams of information from multiple sources simultaneously. In real world
situations, rapidly changing contexts can shift the meaning of a sensory stimulus, requiring an animal to
change its response to a given stimulus on the fly. The ability to flexibly and appropriately adjust behavioral
responses in changing contexts is critical not only for survival, but also to thrive in society. Indeed, disruptions
in this ability characterize many brain disorders. The goal of our lab is to understand the mechanisms that
underlie the flexibility of information processing in cortical circuits, focusing on how inhibitory neurons gate the
flow of information between sensory and association regions in a context-dependent manner. Head-fixed mice
voluntarily running on a spherical treadmill will be rapidly shifted between behavioral contexts within single
sessions. These contexts will include spontaneous (no experimenter-controlled sensory stimulation), passive
delivery of visual and auditory stimuli, and active performance of auditory perceptual tasks in virtual reality. In
each of these contexts, two-photon imaging of calcium activity will be used to monitor the responses of
hundreds of genetically labeled inhibitory and excitatory neurons simultaneously. In some experiments,
optogenetics will be used to activate specific incoming projections to the imaged region, or to inactivate specific
cell types. These tools will be combined in three main projects. In the first project, the inhibitory mechanisms
gating the flow of information between cortical regions will be dissected, to determine whether canonical rules
define inhibitory operations across cortex, or if local specializations allow greater flexibility at different
hierarchical levels of the cerebral cortex. In the second project, the roles of inhibitory neurons in setting
network dynamics will be determined, and the consequences of shifting network dynamics on signal
processing will be defined. In the third project, neuromodulatory recruitment of inhibitory circuits across the
cortical hierarchy will be described, to determine how shifts in brain state affect information processing. To
understand the neural underpinnings of perception, attention, and behavioral flexibility, it is critical to study the
interaction between brain areas, rather than to focus on single brain regions in isolation. The experiments
proposed here will use new tools to answer fundamental questions about how local circuits interact to process
information, toward the goal of understanding how the distributed cortical network gives rise to cognitive
processes such as attention and perception.

## Key facts

- **NIH application ID:** 10478350
- **Project number:** 3DP2MH122404-01S1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Caroline Anne Runyan
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $165,984
- **Award type:** 3
- **Project period:** 2022-01-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10478350

## Citation

> US National Institutes of Health, RePORTER application 10478350, Supplement to Communication between Networks: Context, Inhibition, and Neuromodulation (3DP2MH122404-01S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10478350. Licensed CC0.

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