Lights, Camera, Action

A guide for doing in vivo microscopy on neurons in the mammalian brain

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EYES ON NEURONS: Researchers used a cranial window to look at pyramidal neurons in a mouse cortex, which had been labelled with green fluorescent protein (GFP) using a viral vector. The image is a consolidation of several scanning planes taken up to a few hundred microns deep.COURTESY OF DANIEL LEBRECHT AND ANTHONY HOLTMAATAnimal models have long offered scientists glimpses into the brain. To look at the shapes of neurons, researchers can slice the brains of mice or other animals into thin sections, photographing each one. To monitor the neurons’ activity, they can stick electrodes straight into the brains of anesthetized animals, recording the electrical signals emitted as neurons fire.

But recent advances in neuroscience now allow an unprecedented look at the working brains of living animals. With new lenses and probes, researchers can peer deeper into the brain than ever before. And clever setups are providing a glimpse into the brain activity of rodents as they explore both real and virtual worlds, revealing the neural activity that underlies natural behavior.

“We are now doing experiments on mammals that used to only be possible in insects,” says David Kleinfeld, a neurophysicist at the University of California, San Diego. “It’s a fun time.”

With living models come new challenges. Researchers also need to be surgeons, exposing the brains of mice with dexterity and choosing the approach that is the least likely to damage neurons. And the ...

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