by Li Yang Ku (Gooly)
It might feel like there aren’t that much progress in brain theories recently, we still know very little about how signals are processed in our brain. However, scientists have moved away from sticking electrical probes into cat brains and became quite creative on monitoring brain activities.
Optogenetics techniques, which was first tested in early 2000, allow researchers to activate a neuron in a live brain by light. By controlling the light that activates motor neurons in a mouse, scientists can control its movement remotely, therefore creating a “remote controlled mouse” which you might heard of in some not that popular sci-fi novels. This is achieved by taking the DNA segment of an algae that produces light sensitive proteins and insert it into a specific brain neuron of the mouse using viral vectors. When light is shed on this protein, it opens its ion channel and activates the neuron. The result is pretty cool, but not as precise as your remote control car, yet. (see video below)
Besides the Optogenetics techniques that are used to understand the function of a neuron by actively triggering it, methods for monitoring neuron activities directly have also become quite exciting, such as using genetically modified mice with brain neurons that glow when activated. These approaches that use fluorescent markers to monitor the level of calcium in the cell can be traced back to the green fluorescent proteins introduced by Chalfie etc in 1994. With fluorescent indicators that binds with calcium, researcher can actually see brain activities the first time. A lot of progress have been made on improving these markers since; in 2007 a group in Harvard introduced the “Brainbow” that can generate up to 90 different fluorescent colors. This allowed scientists to identify neuron connection a lot easier and also helped them won a few photo contests.
To better observe these fluorescent protein sensors (calcium imaging), a recent publication in 2016 further introduced the “crystal skull”, an approach that replaces the top skull of a genetically modified mouse with a curved glass. This quite fancy approach allows researchers to monitor half a million brain neuron activities of a live mouse through mounting a fluorescence macroscope on top of the crystal skull.
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Madisen, Linda, et al. “Transgenic mice for intersectional targeting of neural sensors and effectors with high specificity and performance.” Neuron 85.5 (2015): 942-958.
Josh Huang, Z., and Hongkui Zeng. “Genetic approaches to neural circuits in the mouse.” Annual review of neuroscience 36 (2013): 183-215.
Kim, Tony Hyun, et al. “Long-Term Optical Access to an Estimated One Million Neurons in the Live Mouse Cortex.” Cell Reports 17.12 (2016): 3385-3394.