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Nat Nanotechnol. 2019 Aug 19. doi: 10.1038/s41565-019-0521-z. [Epub ahead of print]

Remotely controlled chemomagnetic modulation of targeted neural circuits.

Rao S1,2, Chen R2,3, LaRocca AA4, Christiansen MG1,4,5, Senko AW1,4, Shi CH4, Chiang PH1, Varnavides G1,4,6, Xue J7,8, Zhou Y7,8, Park S1,9, Ding R6,10, Moon J1,4, Feng G7,8, Anikeeva P11,12,13,14.

Author information

1
Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA.
2
Simons Center for Social Brain, Massachusetts Institute of Technology, Cambridge, MA, USA.
3
Department of Bioengineering, Stanford University, Stanford, CA, USA.
4
Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
5
Department of Health Sciences and Technology at the Swiss Federal Institute of Technology in Zürich (ETHZ), Zürich, Switzerland.
6
John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.
7
McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
8
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
9
Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
10
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
11
Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA. anikeeva@mit.edu.
12
Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. anikeeva@mit.edu.
13
McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA. anikeeva@mit.edu.
14
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA. anikeeva@mit.edu.

Abstract

Connecting neural circuit output to behaviour can be facilitated by the precise chemical manipulation of specific cell populations1,2. Engineered receptors exclusively activated by designer small molecules enable manipulation of specific neural pathways3,4. 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 pumps2. 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.

PMID:
31427746
DOI:
10.1038/s41565-019-0521-z

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