Neurotech: Imaging Neurons Deep in A Living Brain

Note: This post first appeared in Scientific American as a part of the Neurotech series.

It’s a Saturday and you’re on vacation, looking out over a beautiful blue Pacific Ocean from the windy cliffs of Big Sur. You breathe in cool, fresh salty air. A thunderous pummel of great waves stirs neural networks in your brain and suddenly you find yourself wondering what lies submerged beneath the foaming sea. Seals playing among beds of kelp? Sharks prowling for a kill? Creatures yet to be discovered?

Exploring beyond what meets the eye has fueled human inventiveness for thousands of years. In recent decades, technology has provided us with unique tools that inspire questions our forefathers could not even begin to imagine.

Consider the brain. A mere 200 years ago, we did not know that it was made of neurons. Without this knowledge, it would be impossible to realize that these cells connect through synapses to form networks and communicate by electrical and chemical signals. The neural doctrine, as it’s called, lead to avalanches of discoveries. One such is plasticity, a neuron’s ability to modify its connections over time. A few decades ago it was widely thought plasticity was exhibited by developing brains and not in adults. But advances in neurotech that allow us to see beyond the surface and venture deep within a living brain disrupted this conception. Researchers now realize that adult brains are highly adaptive to experience and regularly grow new synapses over time.

One integral tool facilitating our ability to track these changes is multiphoton microscopy. It works by shining infrared radiation through tissue, where it is absorbed by fluorescent proteins that have been genetically added to cells. Sensors pick up the emitted fluorescent light and plot the location of fluorescing cells. By directing radiation to focal points at different depths, scientists can chart 3D structure. Repeating this technique over days and weeks allows the identification and monitoring of wiring remodeling dynamics in a living brain.

Seeing subtle neuron rewiring exposes synaptic motility in the brain that was previously unknown. Neurons are not static; spine-like projections in the cortex grow and recede throughout an animal’s life. We can use this technology to detect a wide variety of brain dynamics, such as how synapse growth changes in Alzheimer’s or how cocaine use impacts brain vasculature. Other researchers recently used two-photon microscopy to discover that brain cells shrink by 60% during sleep and are washed in cerebrospinal fluid to remove toxic metabolic byproducts from the day.

We cannot truly understand what we cannot measure. Scientists are beginning to see how external experience is reflected by changes in neural arborization thanks to our ability to map these connections in vivo. This is but the tip of the iceberg. Combining multiphoton microscopy with other neurotechnologies such as optogenetics and electron microscopy stands to reveal ever more details of the brain’s enterprising neural networks. Ralph Waldo Emerson might well have been an observing neuroscientist when he wrote that “what lies behind you and what lies in front of you pales in comparison to what lies inside of you.”

Tune in next week when we explore how high density electrophysiology allows researchers to track the firing of hundreds of cells to understand how coordinated cellular activity can result in behavior and environmental awareness.

Editor’s note: This is the second installment in a series about emerging neurotechnologies. Join a pilot class of 12 PhD students at MIT as we explore how neuroscience is revolutionizing our understanding of the brain. Each post coincides with a lecture and lab tour at MIT created by the Center for Neurobiological Engineering. This experiment is supported by MITx and created by EyeWire.