Sonothermogenetics for noninvasive and cell-type specific deep brain neuromodulation.

Area of Science:

• Neuroscience
• Biotechnology
• Medical Imaging

Background:

• Investigating brain functions and treating disorders is limited by the inability to noninvasively target deep brain neurons.
• Selective neuronal targeting is crucial for advancing neuroscience and neurology.

Purpose of the Study:

• To develop sonothermogenetics, a noninvasive, deep-penetrating, and cell-type-specific neuromodulation technique.
• To combine the thermosensitive ion channel TRPV1 with focused ultrasound (FUS)-induced thermal effects for neuronal activation.

Main Methods:

• In vitro evaluation of TRPV1 sensitivity to FUS sonication.
• In vivo assessment of sonothermogenetics in genetically defined mouse neurons using two-photon calcium imaging.
• Recording behavioral responses to deep brain sonothermogenetic stimulation in freely moving mice and evaluating FUS safety via immunohistochemistry.

Main Results:

• TRPV1 demonstrated ultrasound sensitivity, enabling selective activation of TRPV1-expressing neurons in the mouse brain.
• Precise neuronal activation correlated with FUS-induced temperature, measured by in vivo magnetic resonance thermometry.
• Sonothermogenetic stimulation evoked locomotor behavior, and FUS sonication proved safe for brain tissue.

Conclusions:

• Sonothermogenetics offers a noninvasive, cell-type-specific neuromodulation approach for deep brain stimulation.
• This technique has the potential to advance the study of the intact nervous system.
• It may uncover novel therapeutic strategies for neurological disorders.