# Project 2

> **NIH NIH P50** · STANFORD UNIVERSITY · 2021 · $274,916

## Abstract

Psychoactive and dissociative drugs, such as ketamine, MDMA and methamphetamine, exert powerful
psychological effects by inducing profoundly altered brain states. The popularity of these drugs, their
psychologically and physiologically addictive nature and their rising prevalence as potential therapeutic agents
indicate an urgent need to understand the acute and long-term effects of psychoactive and dissociative 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 the well-defined parahippocampal microcircuit. The neural
basis for the representation of space depends, in part, on neural circuits in the parahippocampal cortex, which
translate the external environment into an internal map of space that supports spatial navigation and memory.
Our preliminary data points to significant effects of ketamine and methamphetamine administration on
parahippocampal circuit codes, which are characterized by cells with highly tractable response properties and a
clear behavioral relevance. Here, we use a highly interdisciplinary approach that combines in vivo
electrophysiology with computational modeling, imaging and behavioral techniques to examine the link between
drug-induced neurocognitive effects and the microcircuits of spatial and memory coding. First, we combine in
vivo physiological, computational and imaging approaches to elucidate whether the microcircuit effects of
ketamine reflect an altered sensory experience or a change in the internal computations that generate spatial
maps. Next, we use high-density in vivo electrophysiology and behavioral paradigms to determine the circuit
and network mechanisms for encoding psychoactive drug associated goals, spatial cues and relapse triggers.
Finally, in vivo electrophysiology is combined with frame-projected independent-fiber photometry to parse out
the circuit basis of MDMA’s pro-social effects. Combined, these studies will provide important insights into the
circuit underpinnings of drug-induced states by leveraging our understanding of the neural codes in a high-order
cortical region crucial to the cognitive processes of memory and self-localization.

## Key facts

- **NIH application ID:** 10149274
- **Project number:** 5P50DA042012-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Lisa Giocomo
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $274,916
- **Award type:** 5
- **Project period:** 2017-08-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10149274

## Citation

> US National Institutes of Health, RePORTER application 10149274, Project 2 (5P50DA042012-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10149274. Licensed CC0.

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