Remotely controlled chemomagnetic modulation of targeted neural circuits

Abstract

Connecting neural circuit output to behaviour can be facilitated by the precise chemical manipulation of specific cell populations. Engineered receptors exclusively activated by designer small molecules enable manipulation of specific neural pathways. However, their application to studies of behaviour has thus far been hampered by a trade-off between the low temporal resolution of systemic injection versus the invasiveness of implanted cannulae or infusion pumps. Here, we developed a remotely controlled chemomagnetic modulation—a nanomaterials-based technique that permits the pharmacological interrogation of targeted neural populations in freely moving subjects. The heat dissipated by magnetic nanoparticles (MNPs) in the presence of alternating magnetic fields (AMFs) triggers small-molecule release from thermally sensitive lipid vesicles with a 20 s latency. Coupled with the chemogenetic activation of engineered receptors, this technique permits the control of specific neurons with temporal and spatial precision. The delivery of chemomagnetic particles to the ventral tegmental area (VTA) allows the remote modulation of motivated behaviour in mice. Furthermore, this chemomagnetic approach activates endogenous circuits by enabling the regulated release of receptor ligands. Applied to an endogenous dopamine receptor D1 (DRD1) agonist in the nucleus accumbens (NAc), a brain area involved in mediating social interactions, chemomagnetic modulation increases sociability in mice. By offering a temporally precise control of specified ligand–receptor interactions in neurons, this approach may facilitate molecular neuroscience studies in behaving organisms.

Publication
Nature nanotechnology
Siyuan Rao
Siyuan Rao
Postdoctoral Fellow

Dr. Rao is a material engineer using her expertise in chemistry and biophysics to invent engineering tools for the study in neuroscience.

Ritchie Chen
Postodoc at Stanford (w/ Karl Deisseroth)
Michael G Christiansen
Postdoc at ETH Zurich (w/ Simone Schuerle)
Alexander W Senko
Data scientist at Livongo
Cindy H Shi
PhD student at Stanford MSE
Pohan Chiang
Assistant Professor at National Chiao Tung University
Georgios Varnavides
Georgios Varnavides
Graduate Student

Full-time graduate student | Part-time design enthusiast | Aspiring cat herder.

Seongjun Park
Assistant Professor at KAIST
Junsang Moon
Junsang Moon
Graduate Student

Graduate Student

Polina Anikeeva
Polina Anikeeva
Associate Professor in Materials Science and Engineering
Associate Professor in Brain and Cognitive Sciences
Associate Director, Research Laboratory of Electronics

My goal is to combine the current knowledge of biology and nanoelectronics to develop materials and devices for minimally invasive treatments for neurological and neuromuscular diseases.

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