SEATTLE — Light from electrons confined by quantum dots has been used to activate and control targeted brain neurons. The method demonstrates a noninvasive way to study how cells communicate and how specific cells may contribute to brain disorders.
It also offers an alternative to electrodes on the scalp or implanted within the brain that deliver zaps of electricity for cell stimulation. Unfortunately, these electrodes activate large areas of neural territory made up of thousands or even millions of cell types.
This makes it impossible to target the behavior of particular cells or cell types to understand cellular communication and how it contributes to brain disorders such as Parkinson's disease, Alzheimer's and severe depression.
For years, researchers have sought methods that can activate nerve cells in a noninvasive and yet highly targeted way. Recently, a team of Stanford University researchers altered mammalian nerve cells to carry light-sensitive proteins from single-celled algae, allowing the scientists to rapidly flip the cells on and off with just flashes of light. The problem with this process, known as photostimulation, however, is that the light-controlled cells must first be genetically altered to flip the switch.
Now a team of scientists at the University of Washington, led by electrical engineer Lih Y. Lin and biophysicist Fred Rieke, has developed an alternative technique that uses quantum dots to confine electrons within three spatial dimensions. When these otherwise trapped electrons are excited by electricity, they emit light, but at very precise wavelengths, determined by both the quantum dot's size and the material from which it is made. Because of this specificity, quantum dots are being explored for a variety of applications, including lasers, optical displays, solar cells, LEDs and even medical imaging devices.
The scientists cultured cells on quantum-dot films so that the cell membranes were in proximity to the quantum-dot-coated surfaces. The electrical behavior of individual cells then was measured as the cells were exposed to flashes of light of various wavelengths; the light excited electrons within the quantum dots, generating electrical fields that triggered spiking in the cells.
Optically excited quantum dots in proximity to a cell control the opening of ion channels. Image adapted from Jiang et al, Chem. Mater., 2006, 18 (20), pp. 4845-4854.
“It is possible to excite neurons and other cells and control their activities remotely using light,” Lin said. “This noninvasive method can provide flexibility in probing and controlling cells at different locations while minimizing undesirable effects.”
“Many brain disorders are caused by imbalanced neural activity,” Rieke said. “Techniques that allow manipulation of the activity of specific types of neurons could permit restoration of normal — balanced — activity levels.” This includes the restoration of function in retinas that have been compromised by various diseases.
“The technique we describe provides an alternative tool for exciting neurons in a spatially and temporally controllable manner,” Rieke said. “This could aid both in understanding the normal activity patterns in neural circuits — by introducing perturbations and monitoring their effect — and how such manipulations could restore normal circuit activity.”
So far, the technique has been applied only to cells cultured outside the body. For the method to be clinically useful and allow insight into disease processes, it must be performed within living tissue.
For this to happen, Lin said the surface of the quantum dots must be modified so that they can target specific cells upon injection into live animals. Additionally, the quantum dots would have to be nontoxic, unlike those used in the experiments, which often had a detrimental effect on the cells to which they were attached.
“One solution would be developing nontoxic quantum dots using silicon,” Lin said.
The work appeared in Biomedical Optics Express
(doi: 10.1364/BOE.3.000 447