Huntington’s Disease: Gene Editing Shows Promise in Mouse Studies

Cas9 clipping the Huntington's repeatsMy father was a folk song collector, and I grew up listening to the music of Woody Guthrie. On July 14th, folk music enthusiasts will be celebrating the 105th anniversary of Guthrie’s birth in his hometown of Okemah, OK. Besides being renowned for writing “This Land is Your Land” and other folk classics, Guthrie has another more tragic claim to fame: he provided the world with a glimpse at the devastation caused by a rare, inherited neurological disorder called Huntington’s disease.

When Guthrie died from complications of Huntington’s a half-century ago, the disease was untreatable. Sadly, it still is. But years of basic science advances, combined with the promise of innovative gene editing systems such as CRISPR/Cas9, are providing renewed hope that we will someday be able to treat or even cure Huntington’s disease, along with many other inherited disorders.

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Snapshots of Life: A Colorful Look Inside the Retina

Mapping neurons in the retina

Credit: Amy Robinson, Alex Norton, William Silversmith, Jinseop Kim, Kisuk Lee, Aleks Zlasteski, Matt Green, Matthew Balkam, Rachel Prentki, Marissa Sorek, Celia David, Devon Jones, and Doug Bland, Massachusetts Institute of Technology, Cambridge, MA; Sebastian Seung, Princeton University, Princeton, NJ

This eerie scene might bring back memories of the computer-generated alien war machines from Steven Spielberg’s War of the Worlds thriller. But what you’re seeing is a computer-generated depiction of a quite different world—the world inside the retina, the light-sensitive tissue that lines the back of the eye. The stilt-legged “creatures” are actually ganglion nerve cells, and what appears to be their long “noses” are fibers that will eventually converge to form the optic nerve that relays visual signals to the brain. The dense, multi-colored mat near the bottom of the image is a region where the ganglia and other types of retinal cells interact to convey visual information.

What I find particularly interesting about this image is that it was produced through the joint efforts of people who played EyeWire, an internet crowdsourcing game developed in the lab of computational neuroscientist Sebastian Seung, now at Princeton University in New Jersey.  Seung and his colleagues created EyeWire using a series of high-resolution microscopic images of the mouse retina, which were digitized into 3D cubes containing dense skeins of branching nerve fibers. It’s at this point where the crowdsourcing came in. Online gamers—most of whom aren’t scientists— volunteered for a challenge that involved mapping the 3D structure of individual nerve cells within these 3D cubes. Players literally colored-in the interiors of the cells and progressively traced their long extensions across the image to distinguish them from their neighbors. Sounds easy, but the branches are exceedingly thin and difficult to follow.

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Watching Neuron Attachments in Real Time

Bright neon yellow and green blob with many light green fingers dotted with green and red radiating from it.

Caption: A living cortical neuron in a culture dish. Red and green dots reveal synapses—potential communication junctions between neurons.
Credit: Don Arnold, University of Southern California

This glittering web is actually a live nerve cell, or neuron, in which its branches are labeled with glowing probes. Each dot reveals a potential junction between neurons—called a synapse—where chemicals are released allowing the cells to talk to each other. The red dots reveal inhibitory synapses—which silence electrical signals—whereas the green dots show the excitatory synapses that promote electrical signals. Continue reading

The Symphony Inside Your Brain

Ever wonder what is it that makes you, you? Depending on whom you ask, there are a lot of different answers, but these days some of the world’s top neuroscientists might say: “You are your connectome.”

Grid of major pathways in human brain’s left hemisphere. Using diffusion spectrum imaging, which tracks movement of water through nerve fibers, researchers can trace groups of neurons as they cross from one region of the brain to another in living individuals. Credit: Van Wedeen, Massachusetts General/Harvard Medical School

The connectome refers to the exquisitely interconnected network of neurons (nerve cells) in your brain. Like the genome, the microbiome, and other exciting “ome” fields, the effort to map the connectome and decipher the electrical signals that zap through it to generate your thoughts, feelings, and behaviors has become possible through development of powerful new tools and technologies.

For some time, neuroscientists have been able to infer loosely the main functions of certain brain regions by studying patients with head injuries, brain tumors, and neurological diseases—or by measuring levels of oxygen or glucose consumption in healthy people’s brains during particular activities. But all along it’s been rather clear that these inferences were overly simplistic.  Now, new advances in computer science, math, and imaging and data visualization are empowering us to study the human brain as an entire organ, and at a level of detail not previously imagined possible in a living person.

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