Schwarz, PhD, is a cell biologist who conducts his research in a cluttered laboratory
overlooking Boston Children’s Hospital. But he likens his scientific approach
to that of the great explorers of the past. “It’s like
marching off into the jungle,” he says, “because you really don’t know what
you’re going to find.”
Schwarz and colleagues at the F.M. Kirby Neurobiology Center have just returned from an “expedition” that could profoundly change our understanding of how the nervous system forms — and give an unexpected new role to an old standby in cell biology: the kinetochore.
In small doses, the anesthetic ketamine is a mildly hallucinogenic party drug known as “Special K.” In even smaller doses, ketamine relieves depression — abruptly and sometimes dramatically, steering some people away from suicidal thoughts. Studies indicate that ketamine works in 60 to 70 percent of people not helped by slower-acting SSRIs, the usual drugs for depression.
Two ketamine-like drugs are in the clinical pipeline, and, as of this week, one appears close to FDA approval. With no significant new antidepressant in more than 30 years, anticipation is high. Yet no one has pinned down how low-dose ketamine works. Studies have implicated various brain neurotransmitters and their receptors — serotonin, dopamine, glutamate, GABA receptors, opioid receptors — but findings have been contradictory.
“We felt it was time to figure this out once and for all,” says neuroscientist Takao Hensch, PhD.
Scientists have known since the 1800s what happens to a totally crushed peripheral nerve in animals: the damaged axons are broken down in a process called Wallerian degeneration, allowing healthy ones to regrow. But humans rarely suffer complete axonal damage. Instead, axons tend to be partially damaged, causing neuropathic pain — a difficult-to-treat, chronic pain associated with nerve trauma, chemotherapy and diabetes.
Microglia are known to be important to brain function. The immune cells have been found to protect the brain from injury and infection and are critical during brain development, helping circuits wire properly. They also seem to play a role in disease — showing up, for example, around brain plaques in people with Alzheimer’s.
It turns out microglia aren’t monolithic. They come in different flavors, and unlike the brain’s neurons, they’re always changing. Tim Hammond, PhD, a neuroscientist in the Stevens lab at Boston Children’s Hospital, showed this in an ambitious study, perhaps the most comprehensive survey of microglia ever conducted. Published last week in Immunity, the findings open a new chapter in brain exploration. …
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.” …