Busy brain

Babies are born with brains that have a lot of circuitry laid down, but it’s not all wired up correctly from the get-go.  Like a young boy scout, the newborn brain is prepared for a lot of possibilities…it just needs a little help organizing.

That organization comes about through trial and error, especially for the visual system of the brain.  That makes sense- there’s nothing to see in utero.  The brain waits until it’s actually receiving input (light), and then trims the chaff soon after birth.  David Hubel and Torsten Wiesel figured out that brains are modified after we’re born in the 1960s; an observation that won them the Nobel Prize a few decades later.

Hubel and Wiesel saw that the brains of monkeys or kittens raised with one eye stitched shut are different from brains of animals raised with both eyes open.  Normally, equal brain space is devoted to processing left-eye information and right-eye information.  When animals are raised with one eye closed, much more space is dedicated to the open eye.  And it’s permanent: when that stitched eye is opened, it is missing appropriate visual processing power in the brain.  The eye can detect light, but the brain misses the signal.  As a result, that “seeing” eye is blind.

We have long understood that there is a critical phase after birth during which the visual system is setting up shop in the brain.  Now a paper published May 24th, 2012 in Neuron by Dorothy Schafer and colleagues in Beth Stevens’s lab at Harvard, describes a possible mechanism for that Nobel-prize winning discovery of fifty years ago.  In it, Schafer and her colleagues describe their findings that microglia, the immune cells of the brain, trim away superfluous connections between neurons to organize the visual sensory system.

As the brain’s immune cells, microglia are obvious first responders to disease and inflammation.  However, their role in healthy brains has only recently been appreciated.  Schafer, et al found that unused connections in the visual processing center of the brain get tagged for removal, and are subsequently eaten up by the microglia.  This idea isn’t such a stretch, since it’s normal for immune cells to “eat up” infected cells and cellular debris.  Apparently, they can also gobble up healthy connections in the brain that aren’t being used. Proper brain function depends the removal of extraneous connections early in development.

Schafer and her colleagues could muck with the system by preventing the microglia from recognizing the “eat me” signal, which led to a messy co-mingling of neurons from the left and right eye in the brain.  Normally, the left- and right-eye neurons are neatly segregated once the microglia have finished tidying up unused connections.

This paper makes use of the visual system of the brain, since it’s easy to manipulate.  Microglia are probably trimming unused connections in other areas of healthy, developing brains.  It will be interesting to see what else microglia turn out to be capable of doing, or not doing, as the case may be: some groups propose that faulty microglia may be partially to blame in neurodevelopmental disorders such as autism.  Swapping out a brain’s faulty microglial population for a new one wouldn’t be easy, but it’s probably not impossible.  If you’re interested, you can read a great article summarizing recent microglial work here.

Every organ system of the body has one or two obvious players.  The brain has neurons.  Those big hitters are what research has mainly focused on to date.  A lot of the peripheral cells were taken for granted:  microglia were “just” immune cells. As technology advances, these bystander cells are turning out to be more interesting than people originally gave them credit for.  A lesson for life in general, perhaps.

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