# Multi-Scale Imaging Core (MSIC)

> **NIH NIH P30** · TRUSTEES OF INDIANA UNIVERSITY · 2024 · $451,319

## Abstract

SPECIFIC AIMS-Multiscale Imaging Core (MSIC)
Addictive substances trigger plasticity at the molecular, cellular and circuit levels that manifest as persistent
behavioral changes that may cause substance use disorders. Targeting these changes may lead to novel
strategies for preventing or treating substance use disorders. However, our knowledge of the molecular changes,
the cellular processes and the abnormal circuit activity patterns that underlie various aspects of substance use
disorders including compulsion, loss of intake control, withdrawal, and relapse is rather limited. To facilitate a
better understanding of the molecular to circuit level plasticity accompanying drug abuse, the C3A multi-
scale imaging core will support center investigators, affiliates from the Midwest and beyond, and trainees at
different career stages to acquire the conceptual and technical know-how, and to access state-of-the-art
equipment for nanoscale molecular measurements, for microscale anatomical analysis of subcellular and
cellular profiles and for mesoscale physiological imaging of brain circuits. The C3A multi-scale imaging core
will provide unprecedented imaging opportunities to examine models of substance use disorders at multiple
levels, including: (1) molecular and cellular level imaging with internationally unique cell-type- and subcellular
compartment-specific correlated STORM super-resolution imaging, and its recently developed
PharmacoSTORM extension for nanoscale pharmacology; (2) circuit level 2P imaging to examine selective
neural circuits and cell-type-specific dynamic physiological changes among large cell populations.
Aim 1. Determine the cell- and subcellular compartment-specific nanoscale molecular and microscale
cellular alterations triggered by chronic exposure to drugs of abuse. By employing fluorescent small
molecule-based PharmacoSTORM single-molecule nanoscale pharmacology and antibody-based
ImmunoSTORM super-resolution imaging, we and C3A-affiliated researchers will determine if chronic drug
exposure and/or withdrawal elicit persistently altered nanoscale distribution and abundance of important
signaling proteins in the cell types and brain circuits that are most relevant for substance use disorders. By
correlating the nanoscale molecular measurements with microscale confocal microscopy data, we will also
establish the associated morphological changes in identified subcellular compartments. Particular attention will
be devoted to CB1 cannabinoid and D3 dopamine receptors that have essential roles in all phases of the addiction
cycle and whose antagonists/negative allosteric modulators are among NIDA’s ten highest medication
development priorities.
Aim 2. Characterize the mesoscale circuit rewiring of long-range glutamatergic, dopaminergic and
serotonergic axons induced by developmental or chronic exposure to drugs of abuse. Axon tracts
connecting distant brain regions follow irregular trajectories, thus white matter morphology is difficu...

## Key facts

- **NIH application ID:** 10898847
- **Project number:** 5P30DA056410-02
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** HUI-CHEN LU
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $451,319
- **Award type:** 5
- **Project period:** 2023-08-15 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898847

## Citation

> US National Institutes of Health, RePORTER application 10898847, Multi-Scale Imaging Core (MSIC) (5P30DA056410-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10898847. Licensed CC0.

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