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A Method for Remotely Silencing Neural Activity in Rodents During Discrete Phases of Learning
Published on: June 22, 2015
Cre-dependent ACR2-expressing reporter mouse strain for efficient long-lasting inhibition of neuronal activity
Yasutaka Mukai1,2, Yan Li1,2, Akiyo Nakamura1
1Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya, 464-8601, Japan.
Abstract:
Optogenetics is a powerful tool for manipulating neuronal activity by light illumination with high temporal and spatial resolution. Anion-channelrhodopsins (ACRs) are light-gated anion channels that allow researchers to efficiently inhibit neuronal activity. A blue light-sensitive ACR2 has recently been used in several in vivo studies; however, the reporter mouse strain expressing ACR2 has not yet been reported. Here, we generated a new reporter mouse strain, LSL-ACR2, in which ACR2 is expressed under the control of Cre recombinase. We crossed this strain with a noradrenergic neuron-specific driver mouse (NAT-Cre) to generate NAT-ACR2 mice. We confirmed Cre-dependent expression and function of ACR2 in the targeted neurons by immunohistochemistry and electrophysiological recordings in vitro, and confirmed physiological function using an in vivo behavioral experiment. Our results show that the LSL-ACR2 mouse strain can be applied for optogenetic inhibition of targeted neurons, particularly for long-lasting continuous inhibition, upon crossing with Cre-driver mouse strains. The LSL-ACR2 strain can be used to prepare transgenic mice with homogenous expression of ACR2 in targeted neurons with a high penetration ratio, good reproducibility, and no tissue invasion.
Insights
Researchers developed a new reporter mouse strain, LSL-ACR2, for optogenetic inhibition. This tool enables precise control of neuronal activity, particularly for long-lasting inhibition, offering high reproducibility and no tissue invasion.
Area of Science:
- Neuroscience
- Genetics
- Optogenetics
Background:
- Optogenetics enables precise control of neuronal activity using light.
- Anion-channelrhodopsins (ACRs) are effective for neuronal inhibition.
- A reporter mouse strain for blue light-sensitive ACR2 was previously unavailable.
Purpose of the Study:
- To generate a novel reporter mouse strain for Cre-dependent expression of ACR2.
- To validate the functionality of ACR2 in targeted neurons.
- To establish a tool for optogenetic inhibition of specific neuronal populations.
Main Methods:
- Generation of the LSL-ACR2 reporter mouse strain.
- Crossing LSL-ACR2 with a noradrenergic neuron-specific Cre driver (NAT-Cre) to create NAT-ACR2 mice.
- Immunohistochemistry, in vitro electrophysiology, and in vivo behavioral experiments to confirm ACR2 expression and function.
Main Results:
- Cre-dependent expression and functional inhibition of ACR2 in targeted neurons were confirmed.
- The NAT-ACR2 mice demonstrated physiological function in vivo.
- The LSL-ACR2 strain allows for homogenous ACR2 expression with high penetration and reproducibility.
Conclusions:
- The LSL-ACR2 mouse strain is a valuable tool for optogenetic inhibition of targeted neurons.
- This strain facilitates long-lasting, continuous neuronal inhibition with minimal invasiveness.
- The LSL-ACR2 strain provides a robust platform for optogenetic research across various Cre-driver lines.
