Our memories, our thoughts and our actions can eventually be traced down to the combination of elementary electric and chemical signals. But monitoring the connections among 100 billion neuron cells is at the very least a daunting endeavour. The first step to solving the brain puzzle consists of the monitoring of electric signals emitted in micron or submicron regions and that vary in time on the scale of milliseconds. A number of nanostructures could be suited for this purpose and, especially encouraged by the launch of the BRAIN Initiative by the Obama administration, nanotechnology researchers have demonstrated various ways in which electrical signals can be recorded.

Perhaps the most successful approach so far has been that of using nanowires, isolated but also in arrays, as electrodes1, with the aim of obtaining direct measurements of neuron electrical activity. While a range of promising results has been achieved, a number of challenges are still present, the most notable being the invasiveness of the nanoprobes, a property that makes them likely to modify the tissue they are supposed to sense2.

In a Perspective published in this issue, Alexander Efros and co-authors examine potentially less invasive approaches based on colloidal quantum dots (QDs)3. These semiconductor nanoparticles are only a few nanometres across, which is comparable to the thickness of the neuron membrane. Both the intensity and wavelength of the fluorescence of a QD are affected by a time-dependent electric field. Experiments have shown that QD luminescence can trace a voltage spike similar to that associated with a firing neuron4. However, QDs should be placed directly inside the neuron membrane, which is challenging for a variety of fundamental reasons. A different strategy is to place the QD outside the membrane and link it to a small donor centre located inside. In this case, the electric field variation affects the donor centre and hence indirectly affects the luminescence of the linked QD. Importantly, this approach has been demonstrated in vivo5.

Though highlighting the first successes, the Perspective has the merit of avoiding hyping their implications. Rather, it provides estimates of the optical requirements necessary for realistic experiments and highlights the numerous challenges, leading to the conclusion that in vivo electrical sensing with QDs is a long-term goal. However, rather than taking this as a negative outcome, we should simply concentrate on the important insight that these nanoparticles can provide through in vitro experiment.