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.


Forget it

Psychologists have been trying to understand why people forget things for more than 100 years.  Do memories just slip away with time?  Are old memories supplanted by new ones?  When these two competing theories were being batted about in the 1920s, the latter won when it was discovered that people remembered more if they memorized a list and then slept, versus memorized a list and stayed awake.  The theory went that sleeping prevented the formation of competing memories.  So it was decided that we forget things because new information kicks out old information.

Then arose a theory that upended that idea.  In it, old memories reach their tentacles forward and prevent the formation of new ones.  This was based on the observation in the late 1950s that college students who memorized lists of nonsense syllables had variable rates of retention.  The students who were repeat test subjects (and so had memorized many lists) fared worse than those who were seeing the lists for the first time.  Clearly, the thinking went, those old lists were throwing their weight around and preventing the brain from memorizing new lists.

By the late 60s/early 70s, psychologists had poked enough holes in all these ideas to necessitate new ones.  So they speculated that memories need time to be cemented in the brain.  According to this, even reading the newspaper interferes with memory formation because the brain’s processing power is distracted from the job of memory consolidation.

While psychologists have been wondering how the box that is your brain gets filled with memories, significant advances have been made in the field of neuroscience to help address this very question.  The most recent discovery describes a cellular mechanism behind the act of forgetting, and goes a long way towards explaining the aforementioned observations of the human condition.

A paper published May 10th, 2012 in Neuron by Ron Davis’s lab at TSRI Florida might bring a collective sigh of relief from the more forgetful of us.  It seems that we were supposed to forget…whatever it was that we forgot.  Davis’s group found that forgetting is an active process, controlled by dopamine. Using fruit flies as their model system, they tested the ability of fruit flies to remember smells.  They found that memory formation involves an initial surge of dopamine, which binds to a dopamine receptor called dA1 and initiates a cascade of events to form a new memory.  Constant, low levels of dopamine are released following the initial surge.  This low-level dopamine is sensed by a different receptor, called DAMB.  Signaling through DAMB causes forgetting.  Unless a memory is assigned some importance and consolidated, DAMB signaling erases it.  The scientists could make fruit flies more or less forgetful by altering DAMB expression on neurons.

What’s really interesting about all of this is that the psychologists’ original observations were not wrong.  Their explanations were just off the mark.  Dopamine, a neurotransmitter with wide-ranging functions, may be differentially regulated by stress, mental exertion, or sleep.  Interestingly, the work by the Davis lab might also explain why some people seem to remember more than others.  Their brains might really be wired differently, with different dopamine receptor levels, for example.

We have a strong desire to understand the human brain.  As neuroscience informs psychology, maybe future experiments on college students will account for what we learn from fruit flies.  If there’s one thing that both fields can agree on, it’s that your brain was designed to forget.