Connectome (9 page)

It's worth pausing to consider how we usually perceive secretions. Spit. Sweat. Urine. We suppress the urge to expectorate in polite company, plug glands with antiperspirants, and flush toilets in quiet privacy. We are embarrassed by secretions, reminders of our flesh and blood. Surely they live in a world apart from entities as ethereal and refined as our thoughts. But the truth is more shocking: The mind depends on an untold number of microscopic emissions. The brain secretes thoughts!

It may seem strange that neurons communicate with chemicals, but we humans do it too. Granted, we rely much more on language or facial expressions. But occasionally we signal each other with smells. While the message of aftershave or perfume is open to interpretation, something along the lines of “I'm sexy” or “Come hither” is a safe guess. Other animals don't have to purchase smell in a bottle. A female dog in heat naturally secretes a chemical signal called a pheromone, which wafts through the neighborhood to bring droves of male dogs by their noses.

Such chemical messages express desire more primitively than Shakespeare's love sonnets. Then again, so do poems that start with “Roses are red, violets are blue.” We should distinguish between the medium and the message. Is there something fundamentally primitive about chemical signals as a medium for communication? There are indeed several limitations, but the brain has found a way to circumvent all of them.

Chemical signals are typically slow. If a woman walks into a room, you will usually hear her footsteps and see her clothing well before you catch a whiff of her perfume. A draft in the room might blow the scent toward you more rapidly, but it will still arrive more slowly than sound and light. Nervous systems, however, generate speedy reactions. When you suddenly jump away from a car piloted by a reckless driver, your neurons signal each other quickly. How can they accomplish this with chemical messages? Think of it this way: Even the slowest runner can finish a race in the blink of an eye if the racetrack is just a few strides long. Though chemical signals may move slowly, the distance that they have to travel across the synaptic cleft is extremely short.

Chemical signals also seem crude because it is difficult to send them to specific targets.
All the partygoers surrounding a woman can smell her perfume. Wouldn't it be more romantic if her fragrance could be sensed only by her beloved? Alas, no inventor has managed to create a scent that is focused in this way. So what keeps the chemical messages at one synapse from spreading like perfume and being sensed by others? The answer is that a synapse “recycles” neurotransmitter by sucking it back up, or degrading it into an inert form, leaving the molecules with little chance to wander. It's no trivial matter for the nervous system to minimize crosstalk
—as engineers call the spreading phenomenon—because synapses are packed so close to each other. With a billion synapses to a cubic millimeter, the brain is far more crowded than Manhattan, and that island's residents often complain about hearing conversations (and much else) from each other's apartments.

Finally, the timing of chemical signals is not easily controlled. A woman's perfume may linger in a room long after she has left the party. The dawdling of neurotransmitter is averted by the same mechanisms of recycling and degradation that squelch crosstalk. This allows chemical messages between neurons to occur at precise times.

These properties of synaptic communication—speed, specificity, and temporal precision—are not shared by other types of chemical communication inside your body. After you jump away from the car in the street, your heart races, you breathe heavily, and your blood pressure skyrockets. This is because your adrenal gland secreted adrenaline into your bloodstream, which was sensed by cells in your heart, lungs, and blood vessels. The reactions of the “adrenaline rush” may seem immediate, but actually they are tardy. They happened
after
you jumped away from the car, because adrenaline spreads through your bloodstream more slowly than signals jump from neuron to neuron.

Secretion of hormones into the blood is the most indiscriminate type of communication, called broadcasting. Just as a television show is received by many households, and a perfume by everyone in a room, a hormone is sensed by many cells in many organs. In contrast, communication at a synapse is restricted to the two neurons involved, just as a telephone call connects the two people on the line. Such point-to-point communication is much more specific than broadcasting.

In addition to chemical signals between neurons, there are also electrical signals in the brain. These travel
within
neurons. Neurites contain salty water rather than metal, but they nonetheless resemble, in both form and function, the telecom wires that crisscross the planet. Electrical signals can travel long distances by propagating through neurites, much as they move along wires. (Interestingly, the mathematical equations developed by Lord Kelvin in the nineteenth century to describe electrical signals in undersea telegraph cables have been used in the modeling of neurites.)

In 1976 the legendary engineer Seymour Cray unveiled one of the most famous supercomputers in history, the Cray-1 (see Figure 16). Some called it the “world's most expensive loveseat,”
and indeed its sleek exterior could have graced the living room of a 1970s playboy. Its interior was anything but sleek, containing 67 miles of tangled wire
in lengths spanning 1 to 4 feet. This looked like a chaotic mess to the casual observer, but actually it was highly ordered. Every wire transmitted information between a specific pair of points chosen by Cray and his design team from locations on thousands of “circuit boards” holding silicon chips. As is common in electronic devices, the wires were wrapped with insulating material
to prevent crosstalk.

 

 

Figure 16. The Cray-1 supercomputer, exterior
(left)
and interior
(right)

 

You may think the Cray-1 looks complex, but it's laughably simple compared with your brain. Consider that
millions
of miles
of gossamer neurites are packed inside your skull, and they are branched rather than straight like wires. The tangle in your brain is far worse than that of the Cray-1. Nevertheless, the electrical signals in different neurites—even adjacent ones—interfere with each other very little, just as in insulated wires. Transmission of signals between neurites occurs only at specific points, those junctions called synapses. Similarly, signals cross from one wire to another in the Cray-1 only at locations where the insulation is removed and the metals come directly into contact.

I've spoken of neurites generically up to now, but many neurons have two types of neurite—dendrites and axon. The dendrites are shorter and thicker. Several emanate from the cell body and branch in its vicinity. A single axon,
long and thin, travels far from the cell body and branches out at its destination.

Dendrites and axons not only look different but play different roles in chemical signaling. Dendrites are on the receiving end of synapses. Their membranes contain the receptor molecules. Axons send signals to other neurons by secreting neurotransmitter at synapses. In other words, the typical synapse is from
axon to dendrite.

The electrical signals of dendrites and axons also differ. In axons, electrical signals are brief pulses known as
action potentials,
each lasting about a millisecond (see Figure 17).
Action potentials are informally known as “spikes,” owing to their pointy appearance, so let's use this nickname for convenience. Neuroscientists often say, “The neuron spiked,” much as a financial reporter writes, “The stock market spiked on bank profits.” When a neuron spikes, it is said to be “active.”

 

 

Figure 17. Action potentials, or “spikes”

 

Spikes are reminiscent of Morse code, which you've probably heard in old movies as a sequence of long and short pulses generated by a telegraph operator pressing a lever. In early telecom systems, pulses were just about the only type of signal that could be heard clearly above the static.
Signals tend to become more corrupted by noise as they travel farther. That's why Morse code was still used for long-distance communication even decades after the telephone became popular for local calls. Nature “invented” the action potential for much the same reason, to transmit information over long distances in the brain. Thus spikes occur mainly in the axon, the longest type of neurite. In small nervous systems like that of
C. elegans
or a fly, neurites are shorter and many neurons do not spike.

So how are these two types of neural communication, chemical and electrical, related? Simply put, a synapse is activated when a passing spike triggers secretion.
On the other side of the synapse, receptors sense neurotransmitter and then make electrical current flow. In more abstract terms, a synapse converts
an electrical signal into a chemical signal and then back into an electrical signal.

Conversion between signal types is common in our everyday technologies. Imagine two people conversing by telephone. Electrical signals travel between them along a continuous wire. (Let's ignore the fact that modern telephone networks additionally use light signals in optical fibers.) But electrical signals do not traverse the narrow gap of air between the handset and the ear; instead, they are converted into acoustic signals. After a journey of a thousand miles as electricity, it is sound that makes the leap to the listener's eardrum. Similarly, an electrical signal may travel far in the brain along an axon, but it does not reach the next neuron directly. Rather, it is converted into a chemical signal, which jumps across the synaptic cleft to the other neuron.

 

If one neuron can signal a second neuron through a synapse, the second neuron can signal a third, and so on. A sequence of such neurons is known as a
pathway.
This is how neurons can communicate with one another even if they are not directly connected by a synapse.

Unlike the mountain paths that we hike, neural pathways are directional. This is because synapses are one-way devices. When there is a synapse between two neurons, we say that they are connected to each other, like two friends talking on the telephone. But the metaphor is flawed, because a telephone transmits information in both directions. At any given synapse, the messages travel one way: One neuron is always the sender, the other always the receiver. This is not because one neuron is “talkative” or the other “taciturn.” Rather, it has to do with the structure of the synapse. The machinery for secreting neurotransmitter is on one side and that for sensing neurotransmitter on the other.

In principle, neurites are two-way devices along which electrical signals can travel in either direction. In practice, a spike normally travels along an axon away from the cell body, and electrical signals travel along dendrites toward the cell body.
Synapses impose this directionality onto neurites. In your circulatory system, blood flows in your veins toward your heart. If a vein were simply a tube, blood could potentially flow in either direction. But a vein also contains valves, which prevent blood from flowing backward. Valves impose directionality on veins in much the same way that synapses impose it on neural pathways.

So a pathway in the nervous system is defined by stepping across synapses from neuron to neuron, respecting the direction of each synapse (see Figure 18). Inside one neuron, electrical signals flow from dendrites to cell body to axon. Chemical signals jump from the axon of this neuron to the dendrite of another neuron. Inside this neuron, electrical signals again flow from dendrites to cell body to axon. They are converted into chemical signals to jump to another neuron, and the process continues. Because the synaptic cleft is extremely narrow, almost all of the distance spanned by the pathway is actually within neurons rather than between neurons. Furthermore, most of this distance runs through axons, which are much longer than dendrites.