# Project 1

> **NIH NIH P50** · STANFORD UNIVERSITY · 2020 · $341,611

## Abstract

Project 1 Summary
Here we implement a technology-driven approach to identify and control circuit dynamics underlying drug-
modulated social and nonsocial behaviors, in contexts carrying reward and risk. We apply technology
representing a major alignment of opportunity for drug abuse research (optoencephalography or OEG, frame-
projected independent-fiber photometry or FIP, and CLARITY-optimized lightsheet microscopy or COLM)
which allow not only observation and control of genetically-defined circuitry, but multiple circuit elements
simultaneously and independently-- before, during and after behaviors in the drug-altered state. In Aim 1, we
begin at the broadest (brainwide) scale in awake rodents, to identify key players and principles in unbiased
fashion, while maintaining circuit element-specificity for observation and control of activity. Technologically,
Aim 1 experiments will include optogenetically-driven precise pulse patterns targeted to specific circuits and
projections, as well as rapid and quantitative COLM- or ofMRI- based assessment of brainwide activity
patterns. These initial unbiased global assessments will powerfully inform and focus more spatially-restricted
investigations in Aims 2 and 3 that resolve essential features of acutely altered states. In Aim 2 we operate at
much higher spatial and temporal resolution, the next step toward detailed elucidation of causal circuit
dynamics in the acutely drug-altered state. For the same drug and behavioral conditions in Aim 1, now
quantitatively guided at the individual-animal level in terms of neuronal activity levels to be targeted using the
population and projection-specific recording capability of FIP, we play-in patterns of population and projection
activity to test causal impact on behavior. And in Aim 3, we leverage the highest-resolution of our new
methods, that nonetheless maintain broad perspective. We are now able to image (with OEG as well as
resonant-scanning two-photon microscopy) large volumes of brain and quantify high-speed dynamical activity
patterns that are cell type-specific, approaching single-cell resolution while maintaining map-like brainwide
perspective, during behavior and during exposure to drugs of abuse. Interventional tests for causality will be
directly guided by these observations. As described below, we have already observed highly specific cortical
activity patterns in response to subanaesthetic ketamine doses, which here will be extended to the same drug
and behavioral conditions pertaining to Aims 1 and 2. This precise observation and control of distinct neural
circuit pathways is tightly intertwined with the research programs described in Projects 2-4, and the
Technology and Training Cores. Together, these experiments in Project 1 will test versatile, powerful new
circuit-dynamics tools for use in the NIDA Center and for the drug abuse community more broadly, and will
also apply these tools to deepen our understanding of acute or chronically-altered d...

## Key facts

- **NIH application ID:** 9962337
- **Project number:** 5P50DA042012-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Karl A. Deisseroth
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $341,611
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962337

## Citation

> US National Institutes of Health, RePORTER application 9962337, Project 1 (5P50DA042012-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9962337. Licensed CC0.

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