By using light to target genetically modified neurons, scientists are demonstrating new and exciting ways to control very specific regions of the brain. Known as optogenetics, this technique has the potential to treat many debilitating health conditions ranging from paralysis to blindness. Scientists at Northwestern University have broken new ground in this area, using a novel implant to program social interactions between mice for the first time, which they say lays the groundwork for understanding the way hierarchies and relationships are formed in complex groups of individuals.
Optogenetics is based on the idea that some cells contain proteins that make them more sensitive to light than others, and by inserting genes that confer these characteristics into new cells, their behavior can be altered when exposed to light. The Northwestern University scientists were able to do this in genetically modified mice by equipping them with altered neurons that expressed a gene from light-sensitive algae, with help from a newly developed brain implant.
This implant is described as the first of its kind. The tiny wireless device is half a millimeter thick, and sits beneath the skin but on the outer surface of the skull. A fine and flexible filamentary probe fitted with LEDs protrudes downward into the brain, with researchers able to operate the light in real-time via wireless near-field communication from a nearby computer.
“With previous technologies, we were unable to observe multiple animals socially interacting in complex environments because they were tethered,” said Northwestern neurobiologist Yevgenia Kozorovitskiy, who designed the experiment. “The fibers would break or the animals would become entangled. In order to ask more complex questions about animal behavior in realistic environments, we needed this innovative wireless technology. It’s tremendous to get away from the tethers.”
The scientists put this new technology to work in experiments where the mice were able to look and behave like normal, enabling them to conduct the first optogenetics study of social interactions between groups of animals.
The implanted rodents were in close proximity to one another inside an enclosure, with the scientists using their technology to activate neurons in the brain region associated with higher order executive function. This led to an increase in the frequency and duration of social interactions between the mice, which was able to be reversed by switching off the stimulation. The scientists could also arbitrarily select a pair of mice for heightened interaction.
“We didn’t actually think this would work,” Kozorovitskiy said. “To our knowledge, this is the first direct evaluation of a major long-standing hypothesis about neural synchrony in social behavior.”
Because optogenetics involves genetically modifying neurons, it is not currently approved for use in humans. What it does do, at least in this context, is offer researchers a way of studying connectivity between neurons in mouse models and the release of neurotransmitters in response to different stimuli.
“Brain activity in an isolated animal is interesting, but going beyond research on individuals to studies of complex, socially interacting groups is one of the most important and exciting frontiers in neuroscience," says John A. Rogers, who led the technology development. "We now have the technology to investigate how bonds form and break between individuals in these groups and to examine how social hierarchies arise from these interactions.”
The research was published in the journal Nature Neuroscience.
Source: Northwestern University