Neuromodulation — the process by which neurons regulate and control other neurons — has long been a topic of interest for researchers developing a means to control neurons artificially, for example, through brain implants.

Whilst for most people this sounds like something from science fiction, brain implants and devices have long been researched for medical applications from monitoring for potential brain aneurysms to treatments for Parkinson’s disease.

Such devices normally come in the form of microchips, or flexible equivalents, but these are limited by the fact that deep-brain monitoring — the probing of the neurons deep below the surface — is largely out of reach for such devices.

Researchers at the City University of Hong Kong have sought to overcome this limitation by using nanoparticles in a novel way.

Publishing in Advanced Healthcare Materials, the team — in collaboration with Sun Yat-Sen University and the Hong Kong Centre for Cerebro-Cardiovascular Health Engineering — used upconversion nanoparticles (UCNPs) to stimulate deep-brain neurons in mice and to control their behavior.

A light touch for neuromodulation

UCNPs are nanoparticles which, when light is shone on them, emit light themselves at a shorter wavelength. These emitted photons can then stimulate neurons — and therefore control them — using a technique called optogenetics.

The team used a “barcode” assembly method for three different UCNPs in a microneedle device that could emit light at 477, 540, and 654 nm, therefore producing a spectra-programmable, spatially selective means of studying and controlling brain circuits.

The UCNPs are biocompatible and their effectiveness was demonstrated in a mouse model. The regions of the mouse brain targeted were those which controlled fear, anxiety, and other defensive behaviors. In a proof-of-concept study, the team were able to selectively stimulate these regions of the brain to make the mice either exhibit freezing behavior or escaping behavior.

The future of optogenetics

As with all new technologies, making sure there is practical use and preventing abuse of the system has been discussed with regards to neuromodulation. Neuromodulation and optogenetics hold great potential for a variety of chronic neurological illnesses, but this same technology also has the potential to control neurological behavior beyond the control of the subject. This is a cause for concern for scientists and policymakers.

It is difficult to hold back the tide of rising technologies, so as machine-brain interfaces and similar neurological technologies become ever-more sophisticated and more research is done in this area, expect more debate about not what is possible with this technology, but how should this technology be used and regulated.

Reference: Peng Shi et al. ‘3D Upconversion Barcodes for Combinatory Wireless Neuromodulation in Behaving Animals‘ Advanced Healthcare Materials (2022) DOI: 10.1002/adhm.202200304