The Mind and the Brain (14 page)

Before exploring further the neuroplasticity of the developing brain, let’s review some basic neurobiology. First, some elementary anatomy: a neuron in the brain consists, typically, of a cell body called the
soma
—Greek for “body”—which measures 10 to 100 micrometers across (100 micrometers equals 0.1 millimeter). The soma contains all the little goodies that keep the cell metabolizing and synthesizing proteins and performing all the other housekeeping functions that cells of all kinds carry out. From the soma sprout numerous multibranched tentacles, called
dendrites
, like snakes from Medusa’s head. The dendrites’ chief function in life is to receive incoming electrochemical messages from other neurons and carry the messages to the cell they’re part of. Dendrites are relatively thick where they emerge from the cell body but divide at dozens if not hundreds of branch points, becoming thinner and wispier each time. The number of dendrites varies tremendously, depending on the function of the cell.

Neurons also sprout from their soma a single
axon
, a long fiber that extends away from the cell body like a string from a balloon and whose job is to carry information to another neuron. This information takes the form of electrical currents. Where an axon from a transmitting neuron terminates on a receiving neuron, it develops special structures, including little holding tanks for neurochemicals. These vesicles release chemicals that transmit messages to the next cell in the circuit. In this way neurons transmit informa
tion along their axons and on to the next neuron. So, again, dendrites receive, axons send. Axons can be as long as a meter, or as short as a few tenths of a millimeter, as are those that carry signals within a single part of the brain. Because these short-axon neurons link neurons locally, they are the most important players in the game of information processing: highly evolved animals have relatively more short-axon neurons than long-axon ones, reflecting their role in integrating and processing information. Exactly how many different types of neurons fill the brain remains an open question, although fifty seems to be a reasonable guess.

Figure 5:
This neuron is typical of those that project from the cortex to the striatum. The inset shows the critical role that calcium ions play in triggering the release of neurotransmitter from vesicles in the presynaptic neuron into the synapse.

Despite their diversity of shape, size, types of connections, and neurochemical content, all neurons carry information in much the same way: they chatter away in electrochemical language. Information transmitted by one neuron and received by another takes the form of electrical signals generated by charged atoms, or
ions
—in particular, positively charged sodium and potassium ions or negatively charged chloride ions. The flux of ions across the cell membrane of a neuron is meticulously regulated by membrane pumps to give the inside of the cell a net negative charge relative to its surroundings. Rapid changes in the flux of ions can
generate a moving pulse of electric charge called an action potential. Like a bulge zipping down a jump rope, the action potential speeds down the axon at up to 200 miles an hour in vertebrates (though only 30 to 40 miles an hour in invertebrates). It is the physical embodiment of the information sent from one neuron to another.

At the end of the axon lies the synapse, which is actually just—well, almost nothing, actually. To be more precise, the
synapse
consists of the axon of a transmitting neuron (called the presynaptic neuron), the dendrite or soma of a receiving neuron (the postsynaptic neuron), and the gap one-millionth of a centimeter wide between them. The synaptic gap, first named by the physiologist Sir Charles Sherrington a century ago, is reminiscent of the almost-touch between the finger of God and the finger of Adam that Michelangelo painted on the ceiling of the Sistine Chapel. For in that achingly close encounter lies a world of potential—in the case of neurons, the potential to hand off the signals that find expression as thoughts, emotions, and sensory perceptions.

Neurons take E. M. Forster’s dictum “Only connect” to extremes. The average brain neuron (insofar as there is such a beast) forms about 1,000 synaptic connections and receives even more. Many neurons receive as many as 10,000 inputs, and some cells of the cerebellum receive up to 100,000. When the pulse of charge arrives at the synapse, it stimulates the entry of calcium ions, which triggers the process by which those tiny vesicles in the presynaptic neuron release neurotransmitters. Since the discovery of the first neurotransmitter in 1921, their number has, as of this writing, topped sixty. Neurotransmitters come in a range of molecular types, from amino acid derivatives to gases like nitric oxide (NO). Because neurotransmitters are the language of neuronal communication in the brain, drugs for mental disorders ranging from depression to anxiety to OCD target them. Valium, for instance, facilitates the effects of the neurotransmitter gamma-aminobutyric acid (GABA).

Molecules of neurotransmitter diffuse across the synapse to the postsynaptic neuron. There, the molecules act as a little armada of space vehicles, docking with tailor-made receptors on the postsynaptic neuron as rovers dock with the mother ship. And, not to belabor the analogy, when the neurotransmitters dock, they unleash a flurry of activity inside the neuron not unlike that unleashed when space pods dock: cascades of very complex molecular interactions including ion fluxes that eventually make the postsynaptic neuron more electrically positive. Once the postsynaptic neuron crosses an electrical threshold, it fires an action potential of its own, shooting it off to the next neuron in the circuit. And the electrochemical activity that underlies the thoughts, emotions, and sensory processing within the brain keeps going.

Although this hurly-burly of electrochemical activity is often thought of as turning on activity in the brain (of being
excitatory
, in neuroparlance), in fact synaptic transmission can also be inhibitory. The preceding example describes an excitatory neuron, in which the released neurotransmitters bind to receptors on the postsynaptic neuron and cause it to become more positive. If it is sufficiently more positive, it fires its own action potential. Inhibitory neurons have an opposite effect. In this case, the flux of ions increases the negative charge across the membrane, thus decreasing the possibility that an action potential will be triggered. Synapses between such neurons are therefore called inhibitory.

One additional concept is necessary for any discussion of neuroplasticity, and this is the notion of altering the strength of synapses. At first blush it seems nonsensical to talk about changing the strength of what is, after all, only a gap. But by “altering synaptic strength,” we mean making the postsynaptic cell more likely to initiate an action potential, and keep the information transmission going, than it was before. This, as far as neuroscientists can tell, is the basis not only of memory but also of the wiring together of millions of neurons into functional circuits. How might such func
tional circuits form? The electrical impulses that shoot down an axon cannot vary in amplitude; neurons either fire or don’t fire (this is known as the all-or-none property of neurons). So if the incoming electrical signal is invariant, then the only plausible suspect for the focus of change induced by neural activity is the synapse.

In 1949, the Canadian psychologist Donald Hebb proposed that learning and memory are based on the strengthening of synapses that occurs when pre- and postsynaptic neurons are simultaneously active. Somehow, he suggested, either the presynaptic neuron or the postsynaptic neuron (or both) changes in such a way that the activation of one cell becomes more likely to cause the other to fire. Although the notion was plausible from the moment Hebb first advanced it, there was not exactly a rush to the lab bench to test it. Hebb, after all, was a mere psychologist, not a neuroscientist. (Hebb was also the first to float the concept, in the late 1940s, of an “enriched environment” as a cause of behavioral improvements—an idea that, in its 1990s incarnation, would launch a thousand
Baby Einstein
videos.) Eventually, however, neuroscientists amassed data showing that Hebb was on to something: electrically stimulating cortical cells to fire simultaneously strengthened their synaptic connections.

As you might guess, this kind of increased synaptic strength is a key to the formation of enduring neuronal circuits and has become known by the maxim “Cells that fire together, wire together.” As best neuroscientists can determine, Hebbian plasticity begins with the release from presynaptic neurons of the neurotransmitter glutamate. The glutamate binds to two kinds of receptors on the postsynaptic neuron. One receptor notes that its own neuron, the postsynaptic one, is active; the other notes which presynaptic neurons are simultaneously active. The postsynaptic neuron therefore detects the simultaneous occurrence of presynaptic and postsynaptic activity. The ultimate result is that a particular action potential whizzing down the axon of a presynaptic neuron becomes more
efficient at causing the postsynaptic neuron to fire. When that happens, we say that there has been an increase in synaptic strength. The two neurons thus become locked in a physiological embrace, allowing the formation of functional circuits during gestation and childhood. The process is analogous to the way that traveling the same dirt road over and over leaves ruts that make it easier to stay in the track on subsequent trips. Similarly, stimulating the same chain of neurons over and over—as when a child memorizes what a cardinal looks like—increases the chances that the circuit will fire all the way through to completion, until the final action potential stimulates the neuron in the language centers and allows the kid to blurt out, “Cardinal!” As a result of Hebbian plasticity, the brain has learned that a crimson bird is called a cardinal. This same pathway crackles with electrical activity whenever you recall a cardinal, and the more you replay this memory, the greater the efficiency with which you can call it up. Changes in synaptic strength thus seem to underlie long-term memory, which must, by its very nature, reflect enduring (if not permanent) changes in the brain regions where memories are stored.

Altering connections in a way that strengthens the efficiency of a neuronal circuit over the long term was the first kind of neuroplasticity to be discovered. Plasticity must be a response to experience; after all, the only thing the brain can know and register about some perception is the pattern of neural activity it induces. This neural representation of the event somehow induces physical changes in the brain at the level of neurons and their synapses. These physical changes “allow the representation of the event to be stored and subsequently recalled,” says Tim Bliss of the National Institute for Medical Research in Mill Hill, England. In a very real sense, these physical changes
are
the memory.

As much as any other neuroscientist, Dr. Eric Kandel of Columbia University has worked out the molecular changes that accompany Hebbian learning and the formation of memories. Kandel works with the unprepossessing creature called
Aplysia californica
,
otherwise known as a sea snail, which resembles nothing so much as a crawling, bruise-colored blob with ears.
Aplysia
’s nerve cells are the largest (as far as scientists know) of any animal’s; actually being able to see what you’re investigating, without having to resort to stains and microscopes, makes the task of working out circuitry a lot simpler. So does having to keep track of a mere 20,000 nerve cells (compared to the 100 billion of the human brain).

Kandel and his colleagues made their first breakthrough when they played Pavlov, and instead of using dogs used
Aplysia
. They sprayed one of the sea snail’s sensitive spots with water—this stimulus makes the creature snap back inside its mantle—and simultaneously gave it an electric shock. The result was sensitization:
Aplysia
jerked back inside its mantle whenever the scientists jolted it ever so slightly. This, in the world of the sea snail, counts as learning:
Aplysia
is remembering that a touch is followed by a nasty shock and so scoots back inside its protective mantle when it experiences the touch. In much the same way, Pavlov’s dogs learned to salivate at the sound of a bell because, during training, food had been paired with that sound.

After identifying the neural circuits underlying this and other simple behaviors, Kandel and a series of collaborators were able to determine how the circuits change as
Aplysia
learns to respond to the different stimuli. They found, for instance, that the sensitized neurons had undergone a long-lasting change: when excited (by the touch), they discharge more neurotransmitter than do neurons of
Aplysia
that have not undergone sensitization. They also found that after a period of stimulation, certain reflex actions can be enhanced for significant periods of time—hours or even days. These stimuli give rise to increased levels of a so-called secondary messenger molecule, called cyclic AMP (or cAMP to its friends). The rise in cAMP levels results in the activation of certain genes in the nucleus of the nerve cell; the gene activation leads to the synthesis of new proteins, some of which appear to play a role in establishing new synaptic connections. It is these connections, neuroscientists now
agree, that are the basis for long-term memory. Experience, then, produces stable, observable changes in what passes for
Aplysia
’s brain, changes that mammals also undergo, as Kandel showed in the 1990s when he added mice to his menagerie of lab animals and replicated the work in rodents.