We Know It When We See It

2 | Neurons That Sing to the Brain

I HAVE TOLD YOU THAT THE WORLD YOU THINK YOU SEE IS NOT THE world that actually exists. It has been altered by your retina, fragmented into dozens of different signals for transmission to the brain. The retina parses the visual image into its most telling components and sends a separate stream of signals about each of them to the brain. The rest is ignored, treated as background noise. This kind of stripped-down signaling, which is a search for economy you’ll hear more about, is not just a result of evolution amusing itself; it is one of the most fundamental principles of all perception.

To see how it happens, we have to get down to basics.

A SINGLE NEURON

A neuron is not a complicated thing. It is a physical object, albeit a very small one, made of materials we understand. It has the normal parts that make up any animal cell, with only a few unique features. When you concatenate a few hundred million neurons, though, big things happen: recognizing a friend, hearing Beethoven, a one-handed catch of a thirty-yard forward pass.

A neuron, like all vertebrate cells, is a bag of water separated from the surrounding water by a thin, fluid membrane. The membrane serves to divide the space inside the cell (black in these drawings) from everything outside it. A few neurons are more or less round, like a kid’s balloon. Others take more complex, amoeboid shapes. Still others can have bizarre and complicated arrangements. Many neurons look like skeletons—a tree in winter. The twigs and branches reflect the neuron’s connections with its near or far neighbors. No matter how baroque the shape, however, the cell always consists of a single space enclosed by a membrane. Its thin twigs enclose long thin spaces, like branching, convoluted soda straws.

What is this cell membrane? It is made of lipid, a variety of fat. Since fat and water do not mix, the cell membrane stays separate, a bit like a soap bubble. By itself, the cell membrane cannot accomplish much of anything. In the lab you can make an artificial cell that has only a cell membrane. Such a cell just sits there. An actual cell membrane is studded with a myriad of fancy little machines that do specific tasks—for example, embedded protein molecules that sense other molecules impinging from outside and then open a gate between the outside and the inside of the cell, which allows an electrical charge to pass. This is the basis of the nerve impulse.

While nerves have an impressive functional repertoire, their main function—the function that distinguishes them from almost all other cells—is to communicate with other neurons. In most cases they do so by transmitting brief impulses of electrical activity, known as spikes. Spikes can travel short distances or long. Some neurons talk to others (we say they “conduct nerve impulses”) only within their own restricted neighborhood. These so-called interneurons (local circuit neurons) signal over distances as small as 10 micrometers, which is just a hundredth of a millimeter. Alternatively, some spikes travel all the way from your brain to the bottom of your spinal cord, as when you seek to wiggle your big toe, or in the reverse direction, as when you stub it on a brick.

Spikes are not electrical currents, like the currents that a copper wire conducts. They are a more complicated biological event, in which the cell membrane actively participates: they are the electrical reflection of the movements of charged ions into and out of the cell, guided by specialized proteins that sit in the cell membrane. For that reason, they travel very slowly compared to electrical conduction down a wire. Nerve impulses travel along an axon at a speed ranging from roughly 10 to 100 meters per second, depending on the axon. Electricity flows down a wire at about 300 million meters per second. From the point of view of our brain’s ability to compute things, this slowness of conduction is a big deal. It is the main reason brains cannot use brute-force, dumb strategies to solve problems.

At the end of the axon is usually a synapse. A synapse allows one neuron to talk to other neurons across the gap that separates them. At the synapse, an electrical signal in one neuron is changed into a chemical signal; specialized synaptic machinery allows the spike to trigger the release of chemicals that are sensed by the second neuron. These are neurotransmitters, about which we hear so much in the news. Because there are lots of different kinds of neurotransmitters, used for different purposes at various places around the brain, and lots of steps involved in their release, this is a point where we can manipulate brain function—for therapeutic goals or for recreation.¹ Nicotine acts on synapses. So do antipsychotic drugs, and those that control epileptic seizures. So does Valium, to make you calm, or Prozac, to make you happy.

A neurotransmitter released by one neuron can make another neuron more excited or less excited. (In reality, a neuron is rarely receiving just a single signal, but for the present purposes let’s just assume it does.) The second neuron integrates all the inputs it receives. When enough impulses reach that neuron within a short time, what we call an “action potential” is triggered in the neuron. That action potential can propagate autonomously within the second neuron and excite or inhibit a third neuron, and so on.

At this point, we see the second big thing neurons do: they decide which inputs to pass on to further neurons and which inputs not to pass on. They make this decision solely by adding up all the inputs the cell receives. This is a bit of a simplification, as the ways in which inputs can be received are wonderfully varied. But to take a simple example, they add excitatory inputs and subtract inhibitory ones. The study of this process constitutes a field of its own within neurobiology; some of my smartest colleagues have spent their lives unraveling the many and elegant ways in which synaptic communication can occur.

Now, though, we’ll think of neurons in their simplest mode, waiting for inputs to come along and firing an action potential when those inputs reach a certain magnitude. But just sending messages from neuron to neuron does not make a brain a brain. It is the combination of neuronal signaling and neuronal decision-making that makes a brain a brain. I’m simplifying because my task here is to tell you about perception. For that, we only need to understand a few things. The most important is that an action potential causes an electrical change wherever it goes. Critically for our story, that electrical change—the spike—can be eavesdropped upon by mortals armed with long thin probes called microelectrodes.

HOW SENSORY NEURONS SIGNAL

As I’ve said, neurons carry messages from place to place over a distance that can be short or long. In a giraffe, the neurons that control walking can span 2.5 meters, reaching from the brain to the lower spinal cord. In all but a few cases, however, the means of signaling is the same: somewhere on the surface of the cell there is a stimulus that initiates an action potential that spreads throughout the neuron.

All neurons that sense the outside world—whether through touch, hearing, vision, or smell—do the same fundamental thing: they detect an event in the world and transmit a signal about it, sometimes with a relay or two, to the brain. But they do this in quite different ways, mirroring the events in the world they are sensing, which are also physically different.

Consider the sense of touch. A perception of touch originates when the skin is deformed through pressure. This could occur by a finger stroking your wrist, a mosquito walking gingerly in search of a soft spot to stab, or your brusque collision with some solid object. These deforming pressures, hard or soft, are detected by nerve endings located just below the surface of the skin. Each ending is part of a neuron.

This image shows two neurons on the touch pathway; the patch of skin, shown by the dashed circle, is known as the receptive field. Information trave from left to right in this diagram. The first neuron has a long fiber (axon) that runs from a place on the skin—where the nerve ending forms many small branchlets—to the spinal cord. When, say, a mosquito lands on your arm, the mosquito’s foot ever so slightly depresses the skin over the nerve ending. That pressure is transmitted to the neuron and a nerve impulse is initiated. That impulse travels along the axon, through the cell body and ends at a synapse (indicated by a forked line) upon another neuron, located in the spinal cord, which then projects to the brain. (Other pathways to the brain exist. This is just one of the simplest.)

The tactile neuron’s branches can detect the indentation of the surface of the skin through what is known as a mechanosensitive ion channel. This channel is a protein in the cell membrane. Deforming the mechanosensitive channel allows positive ions to flow from outside the cell into the nerve ending. The flow of positive ions tends to excite the ending. When the excitation reaches a certain threshold, the ending begins to fire action potentials. These travel up the skin sensory nerve (axon) and past the cell body to a collecting site in the spinal cord, where the axon encounters a second neuron that will transmit the information toward the brain for interpretation. Note that the information from this skin sensory nerve has told the rest of the nervous system three things: that there is something touching your skin, that it is located just above your right wrist, and that the thing is fairly light.

First, the “where,” which is easy. The endings of an individual tactile neuron in the skin cover a limited space on the skin. This space may be tiny, such as on the hand or lip, or broader, such as on the skin of the back. The brain knows what region each nerve surveys, and from that it knows where on the skin the stimulus fell—where the receptive field of that neuron is located.² Obviously, if the stimulus falls on an area of the body like your fingertip, which is covered by many tiny nerve endings, the brain will know more precisely where a small stimulus fell than for places with only a few huge endings, like on your back.

I introduced an important piece of nomenclature when I referred to the dashed circle in the diagram. I called this area under the terminal branchlets of a sensory axon a cell’s receptive field. The receptive field is the specific part of the skin from which a particular sensory axon can be excited. As you will see, we use the same term to talk about vision, where “receptive field” refers to the area of the retina that excites a particular visual neuron—in the retina or later in the visual system.

Now for the “how much” question: how light or heavy the stimulus. How does the skin sensory nerve convey that? All sensory axons—for touch, hearing, vision, smell—communicate with the brain by a coded frequency of action potentials. A light touch produces only a few action potentials; a stronger one produces a more rapid string of them. That’s how the brain, or an experimenter who can monitor the rate of firing, can tell how strong the stimulus was.

Many scientists (including me) have speculated in print that additional information may be contained in the detailed pattern of the action potentials, just as a pattern of key taps conveys information in Morse code.³ The pattern could tell the brain, for example, what type of receptor a particular axon is carrying signals from (see the next paragraph). Certainly the pattern of spikes influences how the brain responds; we know that closely spaced action potentials (spikes) excite the postsynaptic cell more powerfully than widely spaced ones. But nobody has proposed and tested a specific code that has turned out to be convincing.

Even more interesting is the “what” part of our question. The brain wants to know: “What kind of a thing is touching my wrist?” All touches are not created equal. There are several different kinds of touch neurons, responding to different aspects of touch. One type of touch receptor is moderately sensitive to light touch on the surface of the skin and keeps sending a signal to the brain as long as the lightly touching thing is still touching. Another type of receptor responds only to fairly strong pressure and responds only at changes in touch—when the pressure first starts, or when it ends. Presently we know of more than a dozen kinds of primary touch neurons. These can be separately tested in a neurologist’s office. That, in fact, is what she is doing when she compares your sensitivity to a pinprick with your sensitivity to a touch from a buzzing tuning fork.