March 27, 2011 | David F. Coppedge

Neurons Know What to Do

Neurons are among the most vital cells in the body: after all, your brain is largely composed of neurons.  Neurons are transmission lines of information that keep a body in touch with itself and the world.  None of the other body organs would work without neurons.  The increasingly powerful tools of microscopy are allowing neuroscientists to figure out how they develop and operate.

  1. Motors in a network within a network:  In an article entitled “Motors on a mission,” PhysOrg described how the human nervous system, a vast network of billions of neurons, can be conceived as a network of networks: “Within each neuron is a microscopic network of its own, a complex system of signal transmissions.  Proteins receive signals at the cell’s dendrite and transmit them at the axon at the other end, passing the impulses from one neuron to another and allowing human beings to think, perceive and move.
        The network within a single neuron is a system of microtubules.  On these cellular highways, myosin motors carry the molecules of signal transduction from place to place.  Proteins needed by the axons and dendrites are made in the neuron and packaged into bubble-like vesicles, which are carried by various types of myosins.  “Neither the two proteins themselves nor the microtubules know where the proteins should end up,” (after all, they are blind), “so a mix of dendritic and axonal proteins will go both ways, to the dendrite and to the axon,” the article said.
        When a protein ends up at the wrong end, other myosins round up wayward vesicles and turn them back.  Myosin Va acts as a filter at the axons, allowing axon-bound vesicles in but carrying dendrite-bound packages out.  Axonal proteins that end up in a dendrite are placed on the surface of the cell, where Myosin VI plucks them off and carries them to the axon.  Myosin VI also helps axonal proteins find the axon in the first place.  How these molecular machines recognize which is which was not explained.
  2. Hearing in a crowded room:  How do neurons get their information to the right target in the intensely crowded environment of the brain?  It’s like shouting to a friend in a crowded room.  Another article on PhysOrg described how they do it, with the headline, “‘Can you hear me now?’  Researchers detail how neurons decide how to transmit information.”
        The article described how researchers at Carnegie Mellon and U of Pittsburgh are finding out the mechanisms neurons use to communicate.  Neurons can fire separately or together when communicating, like when you shout alone to a friend, or get some friends to shout together.  One researcher explained, “Neurons face a universal communications conundrum.  They can speak together and be heard far and wide, or they can speak individually and say moreBoth are important.  We wanted to find out how neurons choose between these strategies.”  They found that “the brain had a clever strategy for ensuring that the neurons’ message was being heard.” 

    Over the short time scale of a few milliseconds, the brain engaged its inhibitory circuitry to make the neurons fire in synchrony.  This simultaneous, correlated firing creates a loud, but simple, signal.  The effect was much like a crowd at a sporting event chanting, “Let’s go team!”  Over short time intervals, individual neurons produced the same short message, increasing the effectiveness with which activity was transmitted to other brain areas.  The researchers say that in both human and neuronal communication alike, this collective communication works well for simple messages, but not for longer or more complex messages that contain more intricate information.
        The neurons studied used longer timescales (around one second) to convey these more complex concepts.  Over longer time intervals, the inhibitory circuitry generated a form of competition between neurons, so that the more strongly activated neurons silenced the activity of weakly activated neurons, enhancing the differences in their firing rates and making their activity less correlated.  Each neuron was able to communicate a different piece of information about the stimulus without being drowned out by the chatter of competing neurons.  It would be like being in a group where each person spoke in turn.  The room would be much quieter than a sports arena and the immediate audience would be able to listen and learn much more complex information.  (Source: Carnegie Mellon University).

    This effective two-strategy style gave the researchers ideas about designing man-made communication networks around the same principles.

  3. Mapping the brain:  Researchers at the Max Planck Florida Institute spent five years devising methods to map the cerebral cortex, and find how the neurons fit together.  PhysOrg said they identified nine cell types in rat brains, and “were able to quantify the number of neurons per type, their locations within the cortical column and their functional responses to two behavioral states….”  It required terabytes of information for each neuron.  The cerebral cortex in humans is the “largest and most complex area of the brain, whose functions include sensory perception, motor control, and cognition.”
  4. Bilingual neurons:  Neurons used to be classified by the kind of chemical messages, called neurotransmitters, they conveyed.  Now, according to Science Daily, two teams have found neurons that speak two languages; they can use one neurotransmitter at slow speeds, and another at high speeds.  This mechanism, called co-transmission, “allows a single neuron to use two different methods of communication to exchange information.
        Researchers at the University of Montreal found that neurons that typically use dopamine to communicate can also use glutamate for signals needing faster transmission.  Researchers at Douglas Mental Health University Institute also found that neurons that typically use serotonin used to transmit “information for controlling mood, aggression, impulsivity and food intake” are also capable of transmitting “acetylcholine, an important messenger for motor skills and memory.
        A messenger, however, is only as good as the message it carries.  Serotonin, for instance, does not mean “control aggression” in and of itself.  There has to be a convention, a code, an agreement between parties, for something to signal something else and produce a response.
  5. Outside/Inside Learning:  An animal needs to gather information from the outside world and store it in memory.  How this is accomplished was described in another article on PhysOrg about research done by a Swiss team.  “It is well established that environmental enrichment, providing animals with rich sensory, motor, and social stimulation, produces both dramatic increases in the number of synapses in the brain and enhanced learning,” the article began.  This means that outside information produces structural changes on the inside.
        New techniques are allowing scientists to watch the brain form new synapses (the junctions between neurons) in response to environmental signals.  “Remarkably, both the disassembly of pre-existing synapses and the assembly of new synapses were necessary to enhance learning and memory upon environmental enrichment,” they found, adding, “We have shown that circuit remodeling and synaptogenesis processes in the adult have important roles in learning and memory.”  A protein named beta-Adducin is apparently critically important in the formation of new synapses.  For more on synapses, see 12/23/2010.

How did these complex systems come to be?  Another article on PhysOrg titled “The evolution of brain wiring: Navigating to the neocortex” proposed to answer that question from a Darwinian viewpoint.  The lead researcher in Paris wanted to know how axons find their targets.  “The research, published by Cell Press in the March 24 issue of the journal Neuron, reveals a surprising new evolutionary scenario that may help to explain how subtle changes in the migration of ‘guidepost’ neurons underlie major differences in brain connectivity between mammals and nonmammalian vertebrates.”
    Identifying differences, though, does not establish that one group evolved from the other.  Dr. Sonia Garel admitted, “What controls the differential path-finding of thalamic axons in mammals versus nonmammalian vertebrates and how these essential projections have evolved remains unknown,” but then suggested that a protein named Slit2 acts like a molecular switch for guiding developing neurons to their target areas in the brain.  Since Slit2 positions neurons, she thought that minor differences in the resulting positions provides “a novel framework to understand the shaping and evolution of a novel and major brain projection” in different groups of animals.  Why, that might even affect brain connectivity.  A brain permitting her to reason as a neuroscientist could not be far behind: “Since an increase in cell migration has participated in the morphogenesis of the neocortex itself, these novel findings reveal that cell migration can be considered as a general player in the evolutionary changes that led to the emergence of the mammalian brain.

Oh, barf.  There she goes again: scenarios, frameworks for understanding, participants and general players (see personification) and emergence, amply seasoned with maybes and perhaps.  You’re a scientist, aren’t you?  Think, don’t imagine!  Prove your case with facts and evidence.  If imagining scenarios is the new scientific game, we can think of many more that are more entertaining.
    Aside from that brief episode of Malice in Blunderland, this was an amazing series of articles.  Most of them avoided the temptation to insert evolutionary speculation into their work.  Think about it; how a complex set of mechanical processes – motors, chemical signals, guideposts, filters, networks, transmission rules – all converge into the brain of a neuroscientist looking into his or her own head and reasoning about it is astonishing.  In the history of intellectual ideas prior to the invention of the electron microscope and other tools that allow us to see neurons and watch these processes, who could have dreamed such complexity underlies human thought?  We should stand in humble awe at the hardware and software given to our minds and souls to use (02/11/2011, 03/05/2011).
    Incidentally, a human brain said to be 2,500 years old was found in remarkably fresh condition, cerebral folds and all, in a waterlogged pit, reported Live Science.  Aside from the issue that such fragile tissue – usually the first to decay – could survive degradation for so long, this illustrates that it takes more than a brain to think.  You might get a buried car to work again with enough repairs, but the mind or soul – whatever you want to call it – that operated this brain is long gone, even if they could hotwire its neurons once again.  It takes most of a whole body to run a brain, and a brain to run a body.
    Have you ever looked at an X-ray or MRI image of your own brain?  There’s more going on inside than you can possibly imagine (see also 03/24/2011, 12/06/2010, 11/19/2010)  We all have comparable physical equipment; some choose to use it more wisely than others.

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