Wireless Optogenetics for Manipulating Behavior of Mice

Despite decades of intense research since the discovery that new neurons are continuously generated in the adult mammalian brain, their function remains a mystery. Determining the role of neurogenesis in the healthy and diseased brain has broad implications for our understanding of learning, memory, behavior, and regenerative medicine. We are taking advantage of recent advances in optogenetic technology to design tools for studying new neurons in vivo. By combining optogenetics (which uses light to control genetically modified cells) with our lab’s expertise in behavior, we are making progress towards solving one of the biggest mysteries in neuroscience.

 

The ability to label specific populations of neurons with excitatory and inhibitory opsins and then use light to control activation of these selected neurons has tremendous potential for helping us understand how neural circuits control behavior.  However, a major limitation has been the bulky headgear or fiber optic cables that must be mounted into the head to provide light to the neural tissue, and which can severely limit the movement of the animal.  To overcome this obstacle I developed an intensive collaboration with the John Rogers’ group (Professor, Material Sciences) on campus to develop wireless, μLEDs that could be implanted into various different brain regions and illuminated remotely as the animal freely moves through behavioral apparatuses.  After more than 2 years of iterative research between our laboratories, beta testing devices, and developing various transgenic lines of mice for optogenetic manipulations, we now have a few different working applications.  These include transgenic lines of mice that enable the labeling of cohorts of new neurons born during a period of exercise with green fluourescent protein and archeorhodopsin.   These new neurons can then be instantaneously inactivated while the animals are performing a specific behavior through wireless illumination of the implanted μLEDs from the Rogers’ group.  Using this technology we have collected preliminary data that when mice are trained to associate a context with a mild electric shock, their memory of the association is partially dependent on the function of the new neurons labeled during the exercise period.  The result has also provided a validation of the optoelectronic device for inactivating neurons and thereby affecting behavior.  John now has a company, Neurolux, which sells the devices.