Stories about: brain development

Microglia’s role in brain development: A neuroscientist looks back

The journal Neuron, celebrating its 25th anniversary, recently picked one influential neuroscience paper from each year of the publication. In this two-part series, we feature the two Boston Children’s Hospital’s scientists who made the cut. The Q&A below is adapted with kind permission from Cell Press.

Microglial cell with synapses
CAUGHT IN THE ACT: This microglial cell is from the lateral geniculate nucleus, which receives visual input from the eyes. The red and blue are synapses that it has engulfed. (Blue synapses represent inputs from the same-side eye; red, the opposite-side eye.)

In 2012, Beth Stevens, PhD, and colleagues provided a new understanding of how glial cells shape healthy brain development. Glia were once thought to be merely nerve “glue” (the meaning of “glia” from the Greek), serving only to protect and support neurons. “In the field of neuroscience, glia have often been ignored,” Stevens told Vector last year.

No longer. Stevens’s 2012 paper documented that microglia—glial cells best known for their immune function—are no passive bystanders. They get rid of excess connections, or synapses, in the developing brain the same way they’d dispatch an invading pathogen—by eating them.

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Mapping the wiring of the developing brain in 3D

Ed. note: Last week we wrote about Jurriaan Peters, MD’s brain network analysis in children with autism. In the second of our two part series on brain mapping, we talk about ways of mapping the brain’s physical wiring.

(AMagill/Flickr)

At the most basic level, the brain is a collection of wires, albeit a really complex one.

But how during development do nerve fibers thread their way through the growing brain and make the right connections?

The answer to that question could reveal more about the nature of conditions like autism spectrum disorders—which, as we reported about a year and a half ago, seem to have their roots in structurally altered brain pathways.

“We know very little about what’s happening in the developing brain in three dimensions,” says Emi Takahashi, PhD, a researcher in the Fetal-Neonatal Neuroimaging & Developmental Science Center (FNNDSC) at Boston Children’s Hospital. “With histology techniques, we can achieve a two-dimensional view over small areas, but it’s hard to know which fiber bundles are growing in which ways during different stages of development in the whole brain.”

But new MRI-based technologies are quickly closing that knowledge gap, giving us our first high-resolution peek into how the developing brain wires itself up.

Using something called high angular resolution diffusion imaging (HARDI) MRI, Takahashi and her colleagues (including neuroradiologist and FNNDSC director P. Ellen Grant, MD) can trace the three-dimensional pathways within the growing brain via stunning images like these:

Courtesy Cerebral Cortex (Takahashi et al., 2012)

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Could “network” analysis of the brain explain autism’s features?

Ed note: The Obama administration is expected to unveil plans for a decade-long Brain Activity Map project next month. This is Part One of a two-part series on brain mapping.

autism
How is information routed in the brains of children with autism? (Image: Jpatokal/Wikimedia Commons)

It’s now pretty well accepted that autism is a disorder of brain connectivity—demonstrated visually with advanced MRI techniques that can track the paths of nerve fibers. Recent exciting work analyzing EEG recordings supports the idea of altered connectivity, while suggesting the possibility of a diagnostic test for autism.

But what’s happening on a functional level? A study published this week zooms out to take a 30,000-foot view, tracking how the brain routes information in children with autism—in much the way airlines and electrical grids are mapped—and assessing the function of the network as a whole.

“What we found may well change the way we look at the brains of autistic children,” says investigator Jurriaan Peters, MD, of the Department of Neurology at Boston Children’s Hospital.

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Your brain on neglect: The evidence

D Sharon Pruitt/Flickr

If there wasn’t enough reason to be concerned about children suffering psychological and physical neglect—by their family, in foster homes, or from war or weather catastrophes—we now have three good lines of evidence that neglect harms a child’s developing brain.

But there’s also hope that some of this harm can be undone if caught in time.

Impaired IQ

The first evidence comes from cognitive studies done in Romania, where the Bucharest Early Intervention Project (BEIP) has transferred some children reared in its infamous orphanages, selected at random, into quality foster care homes. In 2007, Charles Nelson, PhD, and colleagues documented cognitive impairment in institutionalized children, but also showed improvement when children were placed in good foster homes, especially when they were placed before age 2.

Further evidence—brain imaging—comes from a more recent study by Nelson’s colleague Margaret Sheridan, PhD.

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Immune cells “sculpt” brain circuits — by eating excess connections

The above movie shows an immune cell caught in the act of tending the brain—it’s just eaten away unnecessary connections, or synapses, between neurons.

That’s not something these cells, known as microglia, were previously thought to do. As immune cells, it was thought that their job was to rid the body of unwanted pathogens and debris, by engulfing and digesting them.

The involvement of microglia in the brain’s development has started to be recognized only recently. The latest research finds that microglia tune into the brain’s cues, akin to the way they survey their environment for invading microbes, and get rid of excess synapses the same way they’d dispatch these invaders—by eating them.

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Innovation Day at Children’s Hospital Boston: A preview

Valentine's Day is Innovation Day (image: Richard Giles/Flickr)

In a series of 17 short TED-style talks next Tuesday, February 14, clinicians and scientists from Children’s will present new products, processes and technologies to make health care safer, better and less expensive. The event, from 1-5 p.m. Eastern, is sponsored by the Innovation Acceleration Program. It’s now running a wait list, but you can also watch the live stream or track the proceedings on Twitter (#iDay) or via @science4care. Here’s a small sampling of next week’s presenters; for details, read the press release or view the full agenda.

Diagnosing lazy eye when it’s most treatable: in preschoolers

If lazy eye, or amblyopia, is caught early – ideally, before age 5 – it’s easily treated by patching the “good” eye, forcing the child to use and strengthen the weaker eye. But if it goes unnoticed, the weak, unused eye can slowly go blind,

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Dodging the long-term cognitive effects of early-life seizures

Seizures seem to strengthen and “lock in” synapses too soon, leaving no room for development. (Image: Ice synapses, Joe Flintham/Flickr)

It’s well known that babies who have seizures soon after birth have roughly a 50-50 chance of developing long-term intellectual and memory deficits and cognitive disorders like autism. But until now, it wasn’t understood why these deficits occur, much less how to prevent them from happening.

In the December 14 Journal of Neuroscience, researchers at Children’s Hospital Boston, led by neurologist-neuroscientist Frances Jensen, detail in a rat model how early-life seizures affect brain development at the cellular and molecular level. But more to the point, they show that it might be possible to ward off these effects with drug treatment soon after the seizure – using a drug called NBQX or similar drugs that are already approved by the FDA.

Jenson was particularly interested in what seizures do to synapses, the connections between neurons that are rapidly developing in the infant brain.

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A view of autism: altered brain pathways, disordered white matter

A growing body of evidence from genetic and cell studies indicates that autism spectrum disorders (ASDs) result from abnormalities in how neurons connect to each other to establish brain circuitry. Striking MRI images taken at Children’s Hospital Boston, published in the January Academic Radiology, now strengthen this case visually.

Children’s neurologist-neuroscientist Mustafa Sahin, Simon Warfield, director of the hospital’s Computational Radiology Laboratory, and Jurriaan Peters compared brain organization in 29 healthy subjects with that in 40 patients with tuberous sclerosis, a rare genetic syndrome often associated with cognitive and behavioral deficits, including ASDs about 50 percent of the time. “Patients with tuberous sclerosis can be diagnosed at birth or potentially before birth, because of cardiac tumors that are visible on ultrasound, giving us the opportunity to understand the circuitry of the brain at an early age,” explains Sahin.

The panels above (click to enlarge) are advanced MRI images

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Serendipity in science: Collaborating to build robotic clothing for brain-damaged children

A sequence of motion frames of a normally kicking baby's legs (shown in blue and green), illustrating changing joint angles at the hip and knee.

Countless scientific epiphanies never leave the bench – unless there’s the kind of serendipitous encounter that set Children’s Hospital Boston psychologist Gene Goldfield on a path he never expected to follow.

One in eight babies are born prematurely, putting them at greater risk for cerebral palsy, an inability to fully control their muscles. Goldfield saw these children being wheeled around the hospital, and was convinced that they did not have to be wheelchair-bound.

During early infancy, he knew, the developing brain naturally undergoes a rewiring of its circuits, including those that control the muscles. Could some type of early intervention encourage more typical motor development by replacing damaged circuits with more functional connections?

At Children’s Innovators’ Forum last week, Goldfield discussed his envisioned solution: the use of programmable robots

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Is it really ADHD? Brain activity may provide an objective measure

The right inferior frontal gyrus, part of the prefrontal cortex, lights up on fMRI when children play a game requiring them to resist a natural impulse. This brain area is naturally in flux between ages 5 and 7, Sheridan has found.

Last month, the American Academy of Pediatrics released new guidelines on attention-deficit hyperactivity disorder (ADHD), lowering the minimum age at which physicians should consider drug treatment from 6 years to 4 years.

But here’s the problem. “Current behavioral criteria for ADHD are most effective only after age 8 or 9,” says Margaret Sheridan of the Laboratories of Cognitive Neuroscience at Children’s Hospital Boston. “If you use them at age 3 to 6, then you’re wrong about half the time, and the child will stop meeting the criteria by age 8.”

Little kids, especially boys, are naturally distractible, impulsive and fidgety. Some mature more slowly; some are just the youngest in their class. Many will grow out of their wild but largely age-appropriate behaviors.

But letting true ADHD fester, explaining symptoms away as “kids just being kids,” deprives children of the benefits of behavioral or pharmacologic treatment at a time when their young brains are highly responsive.

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