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Updated: Jun 27, 2025
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A Method for High Fidelity Optogenetic Control of Individual Pyramidal Neurons In vivo
Published on: September 2, 2013
19.1K
Nanoactuator for Neuronal Optoporation.
Marlene E Pfeffer1,2, Mattia Lorenzo DiFrancesco3, Arin Marchesi4,5
1Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Largo Rosanna Benzi 10, 16132 Genova, Italy.
ACS Nano
|April 30, 2024
Summary
Researchers developed a novel nanomachine, BV-1, that uses light to control neuronal activity by forming pores in cell membranes. This allows for precise control over neuronal firing or cell death, offering new tools for neuroscience research.
Area of Science:
- Neuroscience
- Biophysics
- Materials Science
Background:
- High spatial-temporal resolution control of neuronal activity is crucial in neuroscience.
- Optogenetics offers precise control but requires genetic modification; there's a need for non-genetic tools.
- Nongenetic membrane-targeted nanomachines are sought to modulate neuronal electrical states.
Purpose of the Study:
- To engineer and characterize a photoswitchable conjugated compound (BV-1) for light-driven neuronal modulation.
- To investigate the mechanism of BV-1's effect on neuronal membranes.
- To explore BV-1's potential applications in neuroscience, including photostimulation and cell ablation.
Main Methods:
- Engineering and characterization of the photoswitchable compound BV-1.
- Electrophysiological recordings on primary neurons and nonexcitable cells.
- Time-resolved atomic force microscopy and molecular dynamics simulations on lipid bilayers.
- In vivo and ex vivo experiments on retinal explants and primary visual cortex.
Main Results:
- BV-1 spontaneously partitions into neuronal membranes and forms light-induced pores upon cyan light stimulation.
- Light-induced pore formation decreases membrane resistance, increases cation permeability, and causes neuronal depolarization and firing.
- Mechanism involves light-driven oxidation of phospholipids, reduced membrane tension, and increased fluidity.
- BV-1 enables rapid switching to perforated whole-cell patch-clamp configuration and can induce neuronal death with sustained light.
Conclusions:
- BV-1 acts as a versatile molecular nanomachine for light-controlled membrane poration.
- It allows for tunable modulation of neuronal activity, from stimulation to cell death, based on light patterns.
- BV-1 offers a promising non-genetic tool for advanced neuroscience research and potential therapeutic applications.
