Remotely controlled chemomagnetic modulation of targeted neural circuits

• Published in: Nature nanotechnology Vol. 14; no. 10; pp. 967 - 973
• Main Authors: Rao, Siyuan, Chen, Ritchie, LaRocca, Ava A., Christiansen, Michael G., Senko, Alexander W., Shi, Cindy H., Chiang, Po-Han, Varnavides, Georgios, Xue, Jian, Zhou, Yang, Park, Seongjun, Ding, Ruihua, Moon, Junsang, Feng, Guoping, Anikeeva, Polina
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2019; Nature Publishing Group
• Subjects: 631/61/350; 631/61/54/152; 639/301; 639/301/357; 639/925; Animals; Behavior, Animal - drug effects; Cannulae; Cells, Cultured; Chemistry and Materials Science; Circuits; Delayed-Action Preparations - chemistry; Dopamine; Dopamine D1 receptors; Drug Delivery Systems; Interrogation; Latency; Letter; Ligands; Lipids; Liposomes - chemistry; Magnetic Fields; Magnetite Nanoparticles - chemistry; Male; Materials Science; Mice; Mice, Inbred C57BL; Modulation; Nanomaterials; Nanoparticles; Nanotechnology; Nanotechnology and Microengineering; Nerve Net - drug effects; Nerve Net - physiology; Nervous system; Neural networks; Neurons; Neurotransmitter Agents - administration & dosage; Neurotransmitter Agents - pharmacology; Nucleus accumbens; Organic chemistry; Rats; Receptors; Remote control; Social factors; Social interactions; Temperature; Temporal resolution; Ventral Tegmental Area - drug effects; Ventral Tegmental Area - physiology; Ventral tegmentum
• ISSN: 1748-3387; 1748-3395; 1748-3395
• DOI: 10.1038/s41565-019-0521-z

Connecting neural circuit output to behaviour can be facilitated by the precise chemical manipulation of specific cell populations 1 , 2 . Engineered receptors exclusively activated by designer small molecules enable manipulation of specific neural pathways 3 , 4 . 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 2 . 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. Controlled delivery of neuromodulators in the brain might improve the understanding of the molecular basis of behaviour. In this letter, magnetic liposomes injected in deep brain regions release small molecules under remote magnetic stimulation, activating specific neuronal circuits in freely moving mice.