# Neural circuit mechanisms for goal-oriented behavior in novel environments

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $393,541

## Abstract

Project Summary
Humans, like other animals, regularly modify behavior based on environmental context. This relies on the
ability to discriminate between environments and develop strategies for maximizing rewards (or minimizing
punishment) in a context-specific manner. A breakdown in this ability to change behavior depending on
environment is prominent in dementia and Alzheimer's disease. Our central objective is to identify the specific
neuronal circuits and activity dynamics required for acquiring goal-oriented behaviors in novel environments.
We focus on the hippocampus, a region critical for discriminating between environments and necessary for
encoding certain types of behavior. Our central hypothesis is that cell-type specific inhibitory circuits regulate
the pyramidal network dynamics that encode goal-oriented behavior. Specifically, we use in vivo two-photon
calcium imaging to visualize the activity of genetically-defined subsets of hippocampal CA1 neurons as mice
complete goal-oriented tasks in virtual reality (VR) environments, using water rewards for motivation (Arriaga
and Han, J. Neurosci., 2017). With this system, we recently found that both parvalbumin (PV)- and
somatostatin (SOM)-expressing inhibitory interneurons are strongly suppressed in novel environments, with
gradual recovery of activity over days as task performance increases (Arriaga and Han, eLife, 2019). In Aim 1,
we will use a combination of imaging, behavior, and correlative functional and immunolabeling microscopy to
define putative disinhibitory VIP+ neurons activated in novel environments. In Aim 2, we will define the kinetics
of excitatory network reorganization in novel environments during goal-oriented behavior. If inhibitory activity
plays a major role in controlling the encoding of information in excitatory networks, we should see similar
kinetics in activity dynamics across the two networks, i.e. slow stabilization over days. We will track individual
pyramidal neurons during task-engaged behavior in novel environments to define activity dynamics of the
excitatory network. To facilitate this goal, we have developed a neural network-based decoder that tracks the
contribution of individual neurons to population position coding across days. In Aim 3, we will determine the
necessity of inhibition suppression and disinhibition activation for goal-oriented behavior and pyramidal
network reconfiguration. We will test this by chemogenetically restoring inhibitory SOM+ and PV+ interneuron
activity (separately), or silencing PV+ neurons, in novel environments and compare task performance with
control mice. To illuminate possible circuit mechanisms downstream of inhibitory activity manipulation, we will
image excitatory neuron activity to evaluate alterations in network reorganization as defined in Aim 2. This
contribution is significant because it promises to link cell type-specific inhibitory activity with novelty-induced,
pyramidal network reorganization and goal-orient...

## Key facts

- **NIH application ID:** 10034846
- **Project number:** 1R01MH123517-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Edward Bing Han
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $393,541
- **Award type:** 1
- **Project period:** 2020-05-04 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10034846

## Citation

> US National Institutes of Health, RePORTER application 10034846, Neural circuit mechanisms for goal-oriented behavior in novel environments (1R01MH123517-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10034846. Licensed CC0.

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