Connectome (10 page)

 

 

Figure 18. Multineuron pathway in the nervous system

 

If you've eaten poultry, you may have spied bundles of axons on your dinner plate. They are called nerves, and can be recognized as soft whitish strings. They are not to be confused with tendons, which are tougher, or blood vessels, which are darker. Dissecting an uncooked nerve with a very sharp tool causes it to fray, much as a rope unravels into many threads when cut. The “threads” of a nerve are its axons.

Nerves are rooted to the surface of the brain or spinal cord, together known as the central nervous system (CNS). Because most nerves extend and branch toward the surface of the body, they are known as the peripheral nervous system (PNS). The axons in nerves come from cell bodies in the CNS or in little outposts of neurons known as peripheral ganglia. The CNS and the PNS together make up the nervous system, defined alternatively as the set of all neurons and the cells that support them.
The emphasis on nerves in the term
nervous system
is perhaps misleading, as the brain and spinal cord are its predominant parts.

Now let's return to the question posed earlier: How does the sight of a snake cause you to turn and run? The rough answer is that your eyes signal your brain, which signals your spinal cord, which signals your legs. The first step is mediated by the optic nerve, a bundle of a million axons from the eye to the brain. The second step happens through the pyramidal tract, a bundle of axons from the brain to the spinal cord. (A bundle of axons in the CNS is known as a tract rather than a nerve.) The third step passes through the sciatic and other nerves, which connect your spinal cord to your leg muscles.

Let's consider the neurons at the beginning and end of the pathways mediated by these axons. At the back of your eye is a thin sheet of neural tissue called the retina. Light from the snake strikes special neurons in the retina called photoreceptors, which respond by secreting chemical messages, which in turn are sensed by other neurons. More generally, every one of your sense organs contains neurons that are activated by some type of physical stimulus. Sensory neurons kick off the journey along neural pathways from stimulus to response.

These pathways end when axons in nerves make synapses onto muscle fibers,
which respond to secretion of neurotransmitter by contracting. The coordinated contraction of many fibers causes a muscle to shorten and produce a movement. More generally, every one of your muscles is controlled by axons that come from motor neurons. The English scientist Charles Sherrington, who won a Nobel Prize in 1932 and coined the term
synapse,
emphasized that muscles are the final destination of all neural pathways: “To move things
is all that mankind can do . . . for such the sole executant is muscle, whether in whispering a syllable or felling a forest.”

Between sensory and motor neurons there are many pathways, some of which we will consider in detail in later chapters. It's clear that these pathways exist; if they didn't, you wouldn't be able to respond to stimuli. But exactly how do signals travel along pathways?

When California joined the United States in 1850, communicating with the eastern states took weeks. The Pony Express was created in 1860 to speed up mail delivery. Along its two-thousand-mile route from California to Missouri were 190 stations.
A mailbag traveled day and night, switching horses at every station and changing riders every six or seven stations. After reaching Missouri, messages traveled by telegraph to states farther east. The total transit time for a message between the Pacific and the Atlantic was reduced from twenty-three to ten days. The Pony Express operated for only sixteen months before being completely replaced by the first transcontinental telegraph, which in turn was succeeded by telephone and computer networks. The technology may have changed, but the underlying principle has not: A communication network must have a means of relaying messages from station to station along pathways.

It's tempting to think of the nervous system as a communication network that relays spikes from neuron to neuron. A neural pathway would behave like dominoes, with each spike igniting the next spike in the pathway in the same way that each falling domino tips over the next one in the chain. This would explain how your eye tells your legs to move when you see a snake. But in fact it's not that simple. While it's true that an axon relays spikes from the cell body to synapses, it turns out that a synapse does not simply relay spikes to the next neuron.

Almost all synapses are weak.
The secretion of neurotransmitter causes a tiny electrical effect in the next neuron, far below the level required to cause a spike. Imagine a chain of dominoes spaced too far apart. The falling of one won't have any effect on the next. Likewise, a single neural pathway cannot typically relay a spike
on its own—but as I'll explain below, this is a good thing.

 

“Two roads diverged in a yellow wood / And sorry I could not travel both / And be one traveler, long I stood,” wrote Robert Frost in “The Road Not Taken.” A spike does not share Frost's dilemma when it comes to a fork in an axon. Not limited to being “one traveler,” the spike duplicates itself, giving rise to two spikes that take both branches. By doing this repeatedly, a single spike starting near the cell body becomes many spikes that reach every branch of the axon, amplitude undiminished. All of the synapses made by the axon
onto other neurons are stimulated to secrete neurotransmitter.

Through these outgoing synapses, neural pathways diverge like the roads in the poem. That's why stimulating one sense organ can cause multiple responses. The sight of a snake makes you want to run, because of pathways from your eyes to your legs. But the sight of a tasty steak causes your mouth to water, this time thanks to pathways from your eyes to your salivary glands. Because these two types of pathways diverge from the eyes, it's no mystery that either running or salivation is possible after you see something. The mystery is quite the opposite: Why is there only one response? If signals took all possible pathways,
any stimulus would cause every muscle and gland to become activated, and clearly that doesn't happen.

The reason is that signals don't get through pathways so easily. We already saw that single synapses and pathways do not relay spikes. So how do signals ever get through? Although the branches of dendrites look similar to those of axons, their function is completely different. Axons diverge, but dendrites
converge.
Where two branches join, electrical currents can meet as they flow toward the cell body, and can combine like the water of merging streams. And as a lake collects water from many streams, the cell body collects currents from the many synapses converging onto its dendrites.

Why is convergence important? Although a single synapse is typically too weak to drive a neuron to spike,
multiple
converging synapses can do the job. If they are activated simultaneously, they can collectively “convince” a neuron to spike. Because a spike is “all or none,” we can regard it as the output of a “neural decision.” By this metaphor, I do not mean that a neuron is conscious or thinks in the same way that a human does. I simply mean that a neuron is not wishy-washy. There is no such thing as half a spike.

When we're deciding, we may seek advice from friends and family. Similarly, a neuron “listens” to other neurons through its converging synapses. The cell body sums the electrical currents, effectively tallying the votes of the “advisors.” If the tally exceeds a threshold, the axon spikes. The value of this threshold determines whether a neuron decides easily or reluctantly, much as political systems can require a simple majority, a two-thirds majority, or unanimity.

In many neurons, the electrical signals of dendrites are continuously graded, unlike the all-or-none spikes of the axon. This is well suited for representing the entire range of possible vote tallies. A spike in the dendrites would be premature—like calling an election before all the votes are in. Only after the cell body tallies all the votes can spikes occur in the axon. If dendrites lack spikes,
they cannot transmit information over long distances; that's the reason dendrites are much shorter than axons.

One of the basic slogans of a democracy is “One person, one vote.” All votes are weighted equally, as in the neural model above. But we may be less democratic when combining the advice of our friends and family, giving more weight to some opinions than to others. Similarly, a neuron actually weights its “advisors” unequally. Electrical currents have magnitudes. Strong synapses produce large currents in the dendrite, and weak synapses produce small currents. The “strength” of a synapse quantifies the weight
of its vote in the decision of a neuron. And it's possible for a neuron to receive multiple synapses from another neuron, as if allowing it to cast multiple votes—a further kind of favoritism.

We've arrived at the “weighted voting model”
of a neuron. In any type of voting there is some requirement for simultaneity. In politics, this is achieved by asking everyone to go to the polls on a predetermined day. Since synapses can vote at any time, it's always election day in the brain. (Actually, the metaphor is slightly misleading—synaptic votes are tallied over a time period much shorter than a day, ranging from milliseconds
to seconds.) The votes of two synapses are counted in the same tally only if their electrical currents are close enough in time to overlap.

Think of synaptic currents as insults being thrown at someone. Any single insult is too weak to excite a temper tantrum (a spike), so if the insults come only infrequently, the person won't get angry. But if there are many simultaneous insults or if they come in quick succession, they can add up—until the “last straw” pushes the person over the threshold.

 

In the explanation of neural voting I left out an important feature of synapses for the sake of simplicity. It turns out that “yes” votes are not the only kind tallied by neurons. Another kind of synapse registers “no” votes. The yes–no distinction arises because activation of a synapse causes current to flow, and two directions of flow are possible.
Excitatory
synapses say “yes” because they make electrical current flow
into
the receiving neuron, which tends to “excite” spiking.
Inhibitory
synapses say “no” because they make current flow
out
of the neuron, which tends to “inhibit” spiking.

Inhibition is crucial to the operation of the nervous system. Intelligent behavior is not just a matter of making appropriate responses to stimuli. Sometimes it's even more important to
not
do something— not reach for that doughnut when you're on a diet, or not drink another glass of wine at the office holiday party. It's far from clear how these examples of psychological inhibition are related to inhibitory synapses, but it's at least plausible that there's some sort of connection.

The need for inhibition might be the chief reason why the brain relies so heavily on synapses that transmit chemical signals. There is actually another kind of synapse,
one that directly transmits electrical signals without using neurotransmitter. Such electrical synapses work more quickly, since they eliminate the time-consuming steps of converting signals from electrical to chemical and then back to electrical, but there are no inhibitory electrical synapses, only excitatory ones. Perhaps because of this and other limitations,
electrical synapses are much less common than chemical ones.

Given that inhibition is a factor, how should our voting model be revised?
Earlier I mentioned that a neuron spikes when the number of “yes” votes exceeds a threshold. If we include inhibition, spiking happens when “yes” votes exceed “no” votes by some margin set by the threshold. Like their excitatory brethren, inhibitory synapses can be stronger or weaker, so the vote is weighted rather than totally democratic. Some inhibitory synapses are even strong enough to effectively veto many excitatory synapses.

There's one last thing to know about neural voting. Neurons behave like conformists or contrarians, because they too can be classified as either excitatory or inhibitory. An excitatory neuron makes only excitatory synapses
on other neurons, while an inhibitory neuron makes only inhibitory synapses. A similar uniformity
does not hold for the synapses
received
by a neuron, which can be a mixture of excitatory and inhibitory.

In other words, an excitatory neuron either says “yes” to all other neurons by spiking or abstains by remaining silent. Similarly, an inhibitory neuron chooses between “no” and abstaining. A neuron cannot say “yes” to some neurons and “no” to others, or “yes” at some times and “no” at others.

If an excitatory neuron hears many “yes” votes, it also
says
“yes,” conforming to the crowd. If an inhibitory neuron hears many “yes” votes, it says “no,” bucking the trend. In many brain regions, including the cortex, most neurons are excitatory.
You could think of the brain as being like our society, which abounds in conformists but also harbors some contrarians.