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Related Experiment Video

Updated: Jan 25, 2026

Ultrastructural Localization of Endogenous LC3 by On-Section Correlative Light-Electron Microscopy

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Published on: March 31, 2023

Ultrastructural localization of DREADDs in monkeys.

Adriana Galvan^1,2, Jessica Raper¹, Xing Hu¹

¹Yerkes National Primate Research Center, Emory University, Atlanta, Georgia.

The European Journal of Neuroscience

|May 8, 2019

Summary

Designer receptors exclusively activated by designer drugs (DREADDs) expression varies in primate neurons. Tag choice is crucial for effective DREADD membrane localization and function in non-human primates.

Keywords:

HA-tag hM3Dq hM4Di immunogold mCherry

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Non-invasive Strategies for Chronic Manipulation of DREADD-controlled Neuronal Activity

Non-invasive Strategies for Chronic Manipulation of DREADD-controlled Neuronal Activity

Published on: August 25, 2019

Area of Science:

Neuroscience
Molecular Biology
Primate Research

Background:

Designer receptors exclusively activated by designer drugs (DREADDs) are vital tools for neuronal activity modulation in rodents.
Their application in primate research is limited due to insufficient data on membrane expression.
Efficient plasma membrane expression is critical for DREADD functionality.

Purpose of the Study:

To investigate the subcellular localization of AAV-induced DREADDs (hM4Di, hM3Dq) fused to different tags in primate and mouse neurons.
To determine the impact of DREADD/tag combinations on plasma membrane expression in non-human primates.
To provide guidance for optimizing chemogenetic strategies in primate research.

Main Methods:

Electron microscopy immunogold labeling was employed to assess DREADD subcellular localization.
AAV vectors were used to induce DREADD expression in rhesus monkeys and mice.
Specific DREADD constructs (hM4Di-mCherry, hM4Di-HA, hM3Dq-mCherry) were analyzed.

Main Results:

hM4Di-mCherry showed poor plasma membrane expression in monkey neurons but good expression in mice, indicating species-specific differences.
hM4Di fused with a hemagglutinin (HA) tag exhibited strong plasma membrane localization in both monkey and mouse neurons.
hM3Dq-mCherry demonstrated robust plasma membrane expression in monkey neurons.

Conclusions:

The ultrastructural expression of DREADDs in primate neurons is dependent on the specific DREADD/tag combination.
The mCherry tag may hinder hM4Di plasma membrane incorporation in monkeys.
Preliminary characterization of DREADD/tag constructs is recommended for effective chemogenetics in primates.