Abstract
Optogenetics, a widely used technique in neuroscience research, is often limited by its invasive nature of application. Here, we present a noninvasive, ultrasound-based technique to introduce optogenetic channels into the brain by temporarily opening the blood-brain barrier (BBB). We demonstrate the efficiency of the method developed and evaluate the bioactivity of the non-invasively introduced channelrhodopsin channels by performing stimulation in freely behaving mice.
Highlights
With recent advancement in transcranial focused ultrasound (FUS) technology, non-invasive and targeted blood-brain barrier (BBB) opening became possible in several animal models[5,6]
We have introduced and implemented a FUS-based, non-invasive viral delivery technique for optogenetic stimulation
We report comparable volumes of transduction and bioactivity between the FUS method and the commonly used direct infusion technique
Summary
With recent advancement in transcranial focused ultrasound (FUS) technology, non-invasive and targeted BBB opening became possible in several animal models[5,6]. This technique involves a systemic injection of a mixture composed of ultrasound contrast agents (lipid-based microbubbles) and molecules to be delivered. The BBB is temporarily opened and the molecules of interest diffuse into the brain parenchyma according to their concentration gradient[10]. By taking the advantage of the non-invasive nature of the FUS technique, we report here the design and implementation of a FUS-facilitated gene delivery for optogenetic applications. Viral vectors encoding various light-activated protein channels delivered via this approach allow for an entirely non-invasive neural stimulation procedure in vivo
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