To run our circadian clocks, regulate sleep and control hormone levels, we rely on light-sensing neurons known as M1 ganglion cell photoreceptors. Separate from the retina’s rods and cones, M1 cells specialize in “non-image” vision and function even in people who are blind.
Reporting in today’s Cell, neuroscientists at Boston Children’s Hospital describe an unexpected system that M1 cells use to sense changing amounts of environmental illumination. They found that the cells divvy up the job, with particular neurons tuned to different ranges of light intensity.
“As the earth turns, the level of illumination ranges across many orders of magnitude, from starlight to full daylight,” says Michael Do, PhD, of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital, senior author on the paper. “How do you build a sensory system that covers such a broad range? It seems like a straightforward problem, but the solution we found was a lot more complex than expected.” …
The blood-brain barrier was designed by nature to protect the brain and central nervous system (CNS) from toxins and other would-be invaders in the body’s circulating blood. Made up of tightly-packed cells, the barrier allows nutrients to pass into the CNS and waste products from the brain to be flushed out, while blocking entry of harmful substances.
A dysfunctional blood-brain barrier can contribute to CNS diseases including Alzheimer’s and multiple sclerosis (MS). But, ironically, the same blood-brain barrier can keep out drugs intended to treat CNS disease. Scientists have long been seeking ways to overcome this obstacle.
Now, Timothy Hla, PhD, and members of his laboratory in the Boston Children’s Hospital Vascular Biology Program have found a way to selectively control openings in the blood brain barrier to allow passage of small drug molecules. …
But at best, these methods get only about 1 percent of the injured nerve fibers to regenerate and reconnect the retina to the brain. That’s because most of the damaged cells, known as retinal ganglion cells (RGCs), eventually die, says Larry Benowitz, PhD, of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital.
Benowitz and colleagues now show a surprising new approach that gets RGCs to live longer and regenerate robustly: using chelating agents to bind up zinc that’s released as a result of the injury.
These studies, too, were done in mice. If the findings hold up in human studies, they could spell hope for people with optic nerve injury due to trauma, glaucoma or other causes, and possibly even spinal cord injury. …
To the eye, nervous systems look like a tangled mess of neurons and their tree-like branches known as dendrites, but it’s really organized chaos. How the system finds order has intrigued but eluded scientists. In the worm C. elegans, Max Heiman, PhD and graduate student Candice Yip found an elegant system to help explain how neurons each maintain their own space.
Normally, worms have just one neuron of a certain type on either side of their bodies. Yip did a “forward genetic screen” — mutating genes at random to find factors important for neuron wiring. One mutation caused the worm to grow not one set of neurons but five. By engineering the neurons to make a color-changing signal — as shown above — Yip showed that these extra neurons didn’t overlap with each other, but instead carved out discrete territories — a phenomenon known as tiling. How?
Acting on a hunch, Yip and Heiman, of Harvard Medical School and Boston Children’s Hospital’s Division of Genetics and Genomics, showed that C. elegans, faced with an increase in neurons, pressed a molecule called netrin into service to enforce boundaries between them. Netrin is better known for helping nerve fibers navigate to their destinations. When Yip took netrin out of action, the dendrites from the five neurons crossed the invisible borders and grew entangled.
The findings, published today in Cell Reports, could provide insight into neuropsychiatric diseases, believes Heiman, also part of Boston Children’s F.M. Kirby Neurobiology Center. “It’s fundamental to neuropsychiatric disease to make sure brain wiring goes right,” he says. “This is also story about how new features evolve, and how you can form something as complicated as a nervous system. There are pathways that bring everything into order.”
Neurons are more like snowflakes–no two alike–than anyone realized.
Walt Whitman’s famous line, “I am large, I contain multitudes,” has gained a new level of biological relevance in neuroscience.
As we grow, our brain cells develop different genomes from one another, according to new research from Harvard Medical School and Boston Children’s Hospital. The study, published last week in Science, provides the most definitive evidence yet that somatic (post-conception) mutations exist in significant numbers in the brains of healthy people—about 1,500 in each of the neurons they sampled.
The finding confirms previous suspicions and lays the foundation for exploring the role of these non-inherited mutations in human development and disease. Already, the researchers have found evidence that the mutations occur more often in the genes a neuron uses most. And they been able to trace brain-cell lineages based on mutation patterns.
“This work is a proof of principle that if we had unlimited resources, we could actually decode the whole pattern of development of the human brain,” says co-senior investigator Christopher Walsh, MD, PhD, the HMS Bullard Professor of Pediatrics and Neurology and chief of the Division of Genetics and Genomics at Boston Children’s. “These mutations are durable memory for where a cell came from and what it has been up to. I believe this method will also tell us a lot about healthy and unhealthy aging as well as what makes our brains different from those of other animals.” …
When 2015 MacArthur “genius” grant winner Beth Stevens, PhD, began studying the role of glia in the brain in the 1990s, these cells—“glue” from the Greek—weren’t given much thought. Traditionally, glia were thought to merely protect and support neurons, the brain’s real players.
But Stevens, from the Department of Neurology and the F.M. Kirby Neurobiology Center at Boston Children’s Hospital, has made the case that glia are key actors in the brain, not just caretakers. Her work—at the interface between the nervous and immune systems—is helping transform how neurologic disorders like autism, amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and schizophrenia are viewed. …
Dhaka, Bangladesh, is a megacity, one of the world’s fastest growing. By 2025, the U.N. predicts, Dhaka will be home to more than 20 million people as rural migrants swell its population. Many residents live in extreme poverty, crowded into dense, hot, chaotic slums with open sewers and corrugated housing.
While traditional global health programs have focused on curbing infectious disease, low-resource settings like Dhaka are also coming to be seen as “living laboratories” for investigating how adversity affects children’s brain development. Last year, the Bill & Melinda Gates Foundation awarded a two-year, $2.5 million grant to Charles Nelson, PhD, to bring the first fully equipped neuroimaging facility to Bangladesh. …
If you have children present, you might want to click out of this post. But if you want to understand motivation, you’ll want to know about the sexual behavior of fruit flies.
In the brain, motivational states are nature’s way of matching our behaviors to our needs and priorities. But motivation can go awry, and dysfunction of the brain’s motivation machinery may well underlie addiction and mood disorders, says Michael Crickmore, PhD, a researcher in the F.M. Kirby Neurobiology Center. “Basically, every behavior or mood disorder is a disorder of motivation,” he says.
It’s already known that brain cells that communicate via the chemical dopamine are important in motivation—and are also implicated in ADHD, depression, schizophrenia and addiction. But what exactly are these cells up to, and who are they talking to? That’s where fruit flies come in.
“We study motivation in a simple system that we can bash very hard,” says Crickmore. …
Back in the day, the 1980s to be specific, there was a brief fad around amber-on-black computer screens (as opposed to green-on-black or white-on-black) for supposed ergonomic reasons. My computer had one, along with its 5 ¼” floppy drives (remember those?).
More recently, with kids texting at night and people logging late hours on computers and devices, there’s been a recognition that artificial light at night is bad for sleep and disruptive to physiology overall, with blue light increasingly recognized as the culprit.
That’s given birth to some new fads. You can now download programs to eliminate blue light from your computer screen at night or buy amber-tinted glasses for computing and gaming to “filter the harsh spectra” of light. Airlines are using “mood” lighting to mimic sunrises and sunsets, which supposedly reduces jetlag.
DNA sequences were once thought to be the same in every cell, but the story is now known to be more complicated than that. The brain is a case in point: Mutations can arise at different times in brain development and affect only a percentage of neurons, forming a mosaic pattern.
Now, thanks to new technology described last week in Neuron, these subtle “somatic” brain mutations can be mapped spatially across the brain and even have their ancestry traced.
Like my family, who lived in Eastern Europe, migrated to lower Manhattan and branched off to Boston, California and elsewhere, brain mutations can be followed from the original mutant cells as they divide and migrate to their various brain destinations, carrying their altered DNA with them.
“Some mutations may occur on one side of the brain and not the other,” says Christopher Walsh, MD, PhD, chief of Genetics and Genomics at Boston Children’s Hospital and co-senior author on the paper. “Some may be ‘clumped,’ affecting just one gyrus [fold] of the brain, disrupting just a little part of the cortex at a time.” …