There is tremendous interest in mapping all the neuron connections in the human brain with the ultimate goal to better understand how the billions of neurons in the brain communicate with one another during normal brain function, or dysfunction, as result of injury or disease. To do so the global community needs new tools or materials that allow the imaging of large groups of neurons communicating with one another while, at the same time, being able to focus in on a single neuron’s activity. The basis of neuron communication is the time-dependent modulation of the strength of the electric field that is maintained across the cell’s plasma membrane. This is called an action potential.
Among the nanomaterials under consideration for application in neuronal action potential imaging are quantum dots (QDs), crystalline semiconductor nanomaterials possessing a number of advantageous photophysical attributes. Now, a study from researchers at the U.S. Naval Research Laboratory (NRL) have used QDs to track the action potential profile of a firing neuron with millisecond time resolution for the first time. The team state that they are currently on pace to develop the next generation of functional materials using QDs that could enable the mapping of the complex neural connections in the brain. The study is published in the journal Nano Letters.
Previous studies show that QDs are small, bright, photo-stable materials that possess nanosecond fluorescence lifetimes. They can be localized within or on cellular plasma membranes and have low cytotoxicity when interfaced with experimental brain systems. Additionally, QDs possess two-photon action cross-section orders of magnitude larger than organic dyes or fluorescent proteins. Two-photon imaging is the preferred imaging modality for imaging deep into the brain and other tissues of the body. The current study shows the integration of voltage-sensitive nanomaterials into live cells and tissues in a variety of configurations to achieve real-time imaging capabilities not currently possible.
The current study shows that QD brightness tracks, with very high fidelity, the time-resolved electric field strength changes that occur when a neuron undergoes an action potential. Results show that an electric field typical of those found in neuronal membranes results in suppression of the QD photoluminescence (PL) and, for the first time, that QD PL is able to track the action potential profile of a firing neuron with millisecond time resolution.
Data findings show that this effect is connected with electric-field-driven QD ionization and consequent QD PL quenching, in contradiction with conventional wisdom that suppression of the QD PL is attributable to the quantum confined Stark effect, the shifting and splitting of spectral lines of atoms and molecules due to presence of an external electric field. The lab explain that QDs are very bright and photostable and they allow for tissue imaging configurations that are not compatible with current materials, for example, organic dyes. They go on to conclude that their nanoscale size make them ideal nanoscale voltage sensing materials for interfacing with neurons and other electrically active cells for voltage sensing.
The team surmise that the inherent superior photostability properties of QDs coupled with their voltage sensitivity could prove advantageous to long-term imaging capabilities that are not currently attainable using traditional organic voltage sensitive dyes. For the future, the researchers anticipate that continued research will facilitate the rational design and synthesis of voltage-sensitive QD probes that can be integrated in a variety of imaging configurations for the robust functional imaging and sensing of electrically active cells.