The developing brain is constantly forming new connections, or synapses, between nerve cells. Many connections are eventually lost, while others are strengthened. In 2012, Beth Stevens, PhD and her lab at Boston Children’s Hospital showed that microglia, immune cells that live in the brain, prune back unwanted synapses by engulfing or “eating” them. They also identified a set of “eat me” signals required to promote this process: complement proteins, best known for helping the immune system combat infection.
Neuropathic pain is a hard-to-treat chronic pain condition caused by nervous system damage. For people affected, the lightest touch can be intensely painful. A study in today’s Nature may open up a new angle on treatment — and could help explain why mind-body techniques can sometimes help people manage their pain.
“We know that mental activities of the higher brain — cognition, memory, fear, anxiety — can cause you to feel more or less pain,” notes Clifford Woolf, MB, BCh, PhD, director of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital. “Now we’ve confirmed a physiological pathway that may be responsible for the extent of the pain. We have identified a volume control in the brain for pain — now we need to learn how to switch it off.” …
Strabismus is a common condition in which the eyes do not align properly, turning inward, outward, upward or downward. Two to four percent of children have some form of it. Some cases can be treated with glasses or eye patching; other cases require eye muscle surgery. But the treatments don’t address the root causes of strabismus, which experts believe is neurologic.
For decades, Elizabeth Engle, MD, in Boston Children’s Hospital’s F.M. Kirby Neurobiology Center, has been studying rare forms of strabismus, such as Duane syndrome, in which strabismus is caused by limited eye movements. Her lab has identified a variety of genes that, when mutated, disrupt the development of cranial nerves that innervate the eye muscles. These genetic findings have led to many insights about motor neurons and how they develop and grow.
More recently, with postdoctoral research fellow Sherin Shabaan, MD, PhD, Engle’s lab has been gathering families with common, non-paralytic strabismus, in which both eyes have a full, normal range of motion yet do not line up properly.
Such “garden variety” forms of strabismus have been much harder to pin down genetically. …
Electroencephalography (EEG), which records electrical discharges in the brain, is a well-established technique for measuring brain activity. But current EEG electrode arrays, even placed directly on the brain, cannot distinguish the activity of different types of brain cells, instead averaging signals from a general area. Nor is it possible to easily compare EEG data with brain imaging data.
A collaboration between neuroscientist Michela Fagiolini, PhD at Boston Children’s Hospital and engineer Hui Fang, PhD at Northeastern University has led to a highly miniaturized, see-through EEG device. It promises to be much more useful for understanding the brain’s workings. …
In 2011, a team led by Jeffrey Holt, PhD, demonstrated that a protein called TMC1 is required for hearing and balance, following the 2002 discovery that mutations in the TMC1 gene cause deafness. Holt’s team proposed that TMC1 proteins form channels that enable electrically charged ions such as calcium and potassium to enter the delicate hair cells of the inner ear. This, in turn, enables the cells to convert sound waves and head movement into electrical signals that talk to the brain.
In a new study published today in Neuron, Holt and colleagues teamed with the lab of David Corey, PhD, at Harvard Medical School. Together, they confirmed TMC1’s essential role in hearing, ending a 40-year quest, and mapped out its working parts.
Working with living hair cells in mice, they made substitutions in 17 amino acids within the TMC1 protein, one at a time, to see which substitutions altered hair cells’ ability to respond to stimuli and allow the flow of ions. Eleven amino acid substitutions altered the influx of ions, and five did so dramatically, reducing ion flow by up to 80 percent. One substitution blocked calcium flow completely, thereby revealing the location of the pore within TMC1 that enables ion influx.
Down the road, the study could have implications for reversing hearing loss, which affects more than 460 million people worldwide.
“To design optimal treatments for hearing loss, we need to know the molecules and their structures where disease-causing malfunctions arise, and our findings are an important step in that direction,” Holt said in this press release from Harvard Medical School.
Most people with spinal cord injury are paralyzed from the injury site down, even when the cord isn’t completely severed. Why don’t the spared portions of the spinal cord keep working, allowing at least some movement? A new study just published online by Cell provides insight into why these nerve pathways remain quiet. Most intriguingly, it shows that injection with a small-molecule compound can revive these circuits in paralyzed mice — and get them walking again.
“We saw 80 percent of mice treated with this compound recover their stepping ability,” says Zhigang He, PhD, of Boston Children’s Hospital’s F.M. Kirby Neurobiology Center, the study’s senior investigator. “For this fairly severe type of spinal cord injury, this is the most significant functional recovery we know of.” …
Neuropathic pain is chronic pain originating through some malfunction of the nervous system, often triggered by an injury. It causes hypersensitivity to innocuous stimuli and is often extremely debilitating. It doesn’t respond to existing painkillers — even opioids can’t reach it well.
New research in a mouse model, described last week in Cell Reports, deconstructed neuropathic pain and could offer new leads for treating it. The carefully done study showed that two major neuropathic pain symptoms in patients — extreme touch sensitivity and extreme cold sensitivity — operate through separate pathways.
“We think this separation will allow targeted drug-based therapies in the future,” says Michael Costigan, PhD, of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital, who was the study’s senior investigator. “If our results stand experimental scrutiny by others, this will be profoundly important in our overall understanding of neuropathic pain.” …
Babies’ brains are like sponges — highly tuned to incoming sensory information and readily rewiring their circuits. But when so-called critical periods close, our brains lose much of this plasticity. Classic experiments reveal this in the visual system: when kittens and mice had one eye covered shortly after birth, that eye was blind for life, even after the covering was removed. The brain never learned to interpret the visual inputs.
In 2010, a study led by Takao Hensch, PhD, of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital, showed that levels of a protein called Lynx1 rise just as the critical period for visual acuity closes. When the researchers deleted the Lynx1 gene in mice, the critical period reopened and mice recovered vision in the blind eye.
A new study this week in Nature Neuroscience extends Lynx1’s role to the auditory system.
“If we remove Lynx1, the auditory critical period stays open longer,” says Hensch.
Equally important, the study pinpoints the location in the brain where sensory inputs combine with another essential ingredient: what neuroscientists call context. …
Light affects us even without impinging on our awareness. In 1995, Charles Czeisler and colleagues at Harvard Medical School described people who lacked visual perception due to retinal degeneration, but nevertheless responded to light subconsciously — despite being blind, their melatonin level was suppressed, and they appeared to synchronize their circadian clock with the solar day. Across the pond at Oxford, Russell Foster and colleagues were finding the same in mice, and learned that these responses began in the eye.
These discoveries spurred an intense research effort that continues to this day. What system confers subconscious sight, and how does it differ from the system that generates visual experience? …
As the opioid epidemic deepens and drug overdoses increase, effective non-addicting painkillers are desperately needed. Efforts to discover new pain pathways to target with new drugs have thus far had little success. Other promising research is investigating triggerable local delivery systems for non-opioid nerve blockers, but it’s still in the early stages.
A new collaboration between Boston Children’s Hospital and the biopharmaceutical company Amgen is aimed at accelerating new pain treatments. Announced yesterday, it will revolve around patients with rare, perplexing pain syndromes. The scientists hope that the genetic variants they find in these patients will shed new light on pain biology and lead to new ways of controlling pain. …