Improving imaging resolution of the brain

In synapses, electrical signals get converted into chemical ones through the action of neurotransmitters and their receptors. Recent evidence indicates that neurotransmitter receptors diffuse inside and out of synapses, drastically changing the way we understand synaptic transmission and adaptation.

The primary objective of the EU-funded DEEPNMDAR (Deep brain tissue imaging of glutamate NMDAR) project was to study the surface diffusion of the glutamate receptor N-methyl-D-aspartate (NMDAR). Researchers wished to study NMDAR in intact hippocampal slices in their native environment.

For this purpose, they expressed engineered NMDAR in rat hippocampus. To overcome the high background noise associated with single-molecule imaging, they utilised nanoparticles as imaging probes.

Several different types of nanoparticles were synthesised as quantum dots and nanotubes. These were subjected to chemical modifications so that they would react with single molecules in brain cells. Importantly, scientists took extra care to avoid cellular toxicity.

In the end, they selected nanoparticles with good optical properties and optimised the conditions required for single receptor tracking in brain slices.

The next phase of the project entailed the in vivo testing of these nanoprobes in experimental animals. In particular, scientists were able to track individual carbon nanotubes in acute brain slices, which led to the extensive characterisation of the brain extracellular space.

Collectively, the work by DEEPNMDAR successfully demonstrated the potential of nanoprobes for imaging the brain at an unprecedented resolution. The information generated from this sensitive technique will help delineate many previously unknown processes.