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Related Experiment Video

Updated: Nov 4, 2025

Ex Vivo Optogenetic Interrogation of Long-Range Synaptic Transmission and Plasticity from Medial Prefrontal Cortex to Lateral Entorhinal Cortex

Ex Vivo Optogenetic Interrogation of Long-Range Synaptic Transmission and Plasticity from Medial Prefrontal Cortex to Lateral Entorhinal Cortex

Published on: February 25, 2022

Optogenetic strategies for high-efficiency all-optical interrogation using blue-light-sensitive opsins.

Angelo Forli¹, Matteo Pisoni^1,2, Yoav Printz³

¹Optical Approaches to Brain Function Laboratory, Istituto Italiano di Tecnologia, Genova, Italy.

|May 25, 2021

Summary

Researchers developed a new opsin, stCoChR, for precise, low-power, all-optical control of neuronal ensembles. This advancement enables better study of neural networks driving behavior without damaging brain tissue.

Keywords:

CoChR jRCaMP1a mouse mouse cortex neuroscience red-shifted functional indicators soma targeting two-photon optogenetics

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Area of Science:

Neuroscience
Optogenetics
Molecular Biology

Background:

High-resolution all-optical methods are crucial for understanding how neuronal networks control behavior.
Two-photon holographic stimulation requires sensitive actuators to prevent photodamage and heating.
Opsins used for stimulation must not interfere with imaging wavelengths.

Purpose of the Study:

To develop a novel opsin actuator for efficient and safe two-photon holographic stimulation.
To create a soma-targeted opsin variant with improved sensitivity and spectral properties.
To enable precise manipulation of neuronal ensembles in vivo.

Main Methods:

Development of a novel soma-targeted CoChR variant (stCoChR).
In vivo two-photon holographic stimulation of stCoChR in mouse cortex.
Combination with amplified laser stimulation tuned to the opsin absorption peak.
Simultaneous two-photon imaging using a red-shifted indicator (jRCaMP1a).

Main Results:

stCoChR enabled neuronal stimulation with over 10-fold lower average power compared to previous opsins.
Demonstrated no spectral crosstalk between stimulation and imaging.
Achieved high-sensitivity and precise control of neuronal ensembles.
Validated in vivo performance in the mouse cortex.

Conclusions:

stCoChR is a highly sensitive and spectrally compatible opsin for two-photon holographic stimulation.
The combination of stCoChR, amplified laser, and red-shifted indicators is a powerful tool for neural network interrogation.
This technology advances the study of neural circuits and their role in behavior.
Offers a safer and more efficient method for large-scale neural network manipulation.