# Brain-wide circuits for drug-induced changes to cognition

> **NIH NIH P50** · STANFORD UNIVERSITY · 2024 · $296,313

## Abstract

PROJECT SUMMARY (Project 2)
Dissociative and non-dissociative drugs, such as ketamine, PCP, methamphetamine and morphine, exert
powerful psychological effects by inducing profoundly altered brain states. The popularity of these drugs, their
psychologically and physiologically addictive nature and the rising prevalence of a subclass of dissociative drugs
as potential therapeutic agents indicate an urgent need to understand the acute and long-term effects of these
drugs on brain-states. A large gap exists however, in our understanding of the circuit mechanisms underlying
drug-altered states themselves. To bridge this gap, we seek to elucidate the molecular, circuit and network
mechanisms of drug induced cognitive states by taking advantage of a set of highly tractable response properties
of neurons across the multiple brain regions that support spatial cognition. Our focus on spatial cognition is
motivated by the shared capability of dissociative and non-dissociative drugs to alter neural representations of
space. Dissociative drugs are well documented to induce out-of-body experiences and can impair spatial
memory. Non-dissociative drugs of abuse can leverage the spatial memory system to encode drug-context
associations, leading to drug-associated contexts serving as a potent trigger for relapse to drug use. However,
the brain-wide circuit mechanisms underlying these alterations in spatial cognition, as well as how this impacts
behavior, remain incompletely understood. Here, we use cutting-edge large scale in vivo electrophysiology
combine with behavioral techniques to examine the link between drug-induced spatial cognitive effects and the
microcircuits of spatial and memory coding. First, we perform wide-scale electrophysiology to measure the
neural correlates of spatial estimates in multiple cortical and sub-cortical brain regions during navigation to
investigate how dissociative and non-dissociative drugs induce changes in spatial cognition. Next, we hone in
on particular brain regions of interest in freely moving animals to examine how dissociative and non-dissociative
drugs drive changes in the neural correlates of behavior in spatial tasks. Finally, in vivo electrophysiology is
combined with genetic and behavioral approaches to parse out the molecular basis of ketamine’s potentially
therapeutic versus negative effects on spatial cognition. Together, this work will provide new insight regarding
the brain wide-circuit mechanisms for cognitive states associated with drugs of addiction and the behavioral
impacts of these drug-induced cognitive states on spatial memory and navigational behavior.
.

## Key facts

- **NIH application ID:** 10917023
- **Project number:** 5P50DA042012-07
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Lisa Giocomo
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $296,313
- **Award type:** 5
- **Project period:** 2017-09-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10917023

## Citation

> US National Institutes of Health, RePORTER application 10917023, Brain-wide circuits for drug-induced changes to cognition (5P50DA042012-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10917023. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*