The Nervous System - 1

Suppose that you are sitting in your chair during a slow lecture on the nervous system. You notice out of the corner of your eye a dark, furry object resting on your forearm. What you are most likely to do is instantly flick the object off your forearm!

You might then go find the furry object, only to discover that it was piece of thread that had come loose from your blouse. Smiling to yourself as you return to your seat, you realize that your heart is beating a little faster.

All of this stuff, the glimpse of the furry object, the rapid flick to get rid of it, the curiosity on your part, the increase in your heart rate, all are manifestations of your nervous system in operation.

Your nervous system regulates your body's activities and fosters homeostasis. Without continued neural activity, you, as an organism, cannot survive. Your nervous system controls musculature, affects your lung operation, regulates your sweat glands to control release of heat, allows chewing and digestion.

Also controlled by your nervous system are very basic drives such as hunger, thirst and sexual desires. Consciousness itself is derived from nervous activity.

And to make it all the more interesting for biologists, the nervous system is one of our last poorly understood knowledge areas. We really don't understand the neural basis of thought, learning, memory, perception or behavior. This makes it a very fertile field for research.

Nerve cells or neurons are specialized for conducting messages as moving impulses. The messages sent move fairly rapidly (about 225 miles per hour). And, the overall effect of such impulses depends on the nature of the neuron and the kind of target cell that responds to the neuron.

Some neurons are excitatory neurons and stimulate their target cells into activity. Other neurons are inhibitory neurons, and encourage their target cells to rest.

There are three fundamental types of target cells that can respond directly to a neuronal impulse. These are:

• muscle cells - they respond to nervous stimuli by contracting
• gland cells - they respond to nervous stimuli by secreting substances
• other nerve cells - they respond by generating impulses of their own which may then be passed on to some target cell

We immediately run into the typical cell conundrum when we try to describe a typical nerve cell. A human body contains more than 100 billion neurons and no two are exactly alike.

Neuronal form is closely correlated with function. The nucleus of a neuron is located in an expanded region of the cell referred to as the cell body. Extending from the cell body are numerous fine projections called dendrites which receive incoming information from external sources such as other neurons.

Also projecting from the cell body is a single, more prominent extension, the axon. Axons conduct outgoing impulses away from the cell body toward a target cell.

Some axons are not very long; others are quite long and comprise some of the largest cells in the human body. Consider the axons that radiate from your spinal cord to your legs.

Most axons split near their ends into a number of processes each in turn ending in a structure called a synaptic knob. Synaptic knobs are specialized sites where impulses are transmitted from neuron to target cell.

Only about 10% of the cells in the human nervous system are neurons. The rest are the so-called supporting cast-- neuroglial cells. Schwann cells are one type of supporting cast cell.

Mostly plasma membrane with very little cytoplasm, Schwann cells wrap themselves around axons, forming a layered jacket of cell membranes that is referred to as a myelin sheath.

You will recall that cell membranes are mostly made of lipids. Lipids are rather poor conductors of electricity and so, the myelin sheath material acts as insulation along the "wire conductors," the axons, of neurons.

Interestingly, the insulation is not a continuous layer. Along the length of an axon, naked gaps are present. These uninsulated gaps are called nodes of Ranvier and are involved in a speed-up mechanism of nerve impulses along the axon.

We often compare the propagation of a nerve impulse along a neuron with the conduction of an electric pulse along a copper wire. This analogy fails. Nerve propagation is different.

Movement of an electric pulse along a wire involves the movement of electrons along the wire.

A nerve impulse does not involve the movement of electrons or the flow of any charged particles along an axon. Instead, a nerve impulse is the result of movement of ions across the axon plasma membrane.

This is a very important difference and should lead you to the question of just how ionic movement across the axon membrane at one point can lead to a nervous impulse that moves at a fair velocity along the axon to a target cell.

Here is how it works. The concentrations of specific ions on the two sides of the axon plasma membrane of a resting neuron (one not conducting an impulse) are very different.

The concentration of potassium ions (K⁺) is approximately 30 times greater inside the cell than outside. The concentration of sodium (Na⁺) and chloride (Cl^-) ions are approximately 10-15 times greater outside of the cell then inside.

These ionic gradients are established by membrane "pumps."

You might expect that because of their concentration gradients, potassium ions would diffuse out of the cell and sodium and chloride ions would diffuse into the cell. But such diffusion depends on the permeability of the plasma membrane. Ions are able to move across the plasma membrane only through specific "channels."

Nerve cells have two types of channels-- leak channels which are always open and gated channels which can be either open or closed.

In a resting neuron, potassium ions diffuse out of a cell through potassium leak channels. There are no sodium leak channels making the plasma membrane essentially impermeable to sodium ions.

Potassium ions are positively charged and their movement out of the cell through the potassium leak channels leaves the inside of the membrane more negatively charged than the outside.

This separation of positive and negative charge is called a potential difference or voltage. A resting cell has a potential difference of about -70 millivolts. The negative sign indicates the negativity of the inside of the cell relative to the outside of the cell.

If you stimulate a neuron in some manner, the axon responds by opening the gates of some of its sodium channels, allowing sodium ions to move into the cell. This movement of positively charged material into the cell reduces the membrane potential or voltage making it less negative. This is sometimes referred to as depolarization.

If the stimulus is brief and the membrane potential depolarizes by only a few millivolts, say from -70 to -50 millivolts, the membrane rapidly returns to its resting potential.

If the stimulus is sufficient, however, the depolarization continues beyond a particular point referred to as the threshold and a new series of events begins.

The gates on the sodium channels swing open and sodium ions rush into the cell. As this occurs, the membrane potential momentarily reverses itself and becomes a positive potential of perhaps +50 millivolts.

Then, the sodium gates close and the gated potassium channels open and potassium ions flood out of the cell, re-establishing the negative membrane potential. This re-polarizes the membrane.

These changes in membrane potential are collectively referred to as an action potential. The entire sequence of events occurs in a few thousandths of a second. Take a look at this diagram for a re-phrasing of these events.

You might wonder how xylocaine or novocaine works. This is the stuff that dentists inject to numb your jaw before they begin their drilling operations on your teeth.

Most of you have stacked dominos near one another and knocked one down which led to all of the others falling down. An action potential initiated works something like dominos, cascading down the entire length of a neuron. Once an action potential is triggered, it passes down an axon without any loss of intensity to its target cell.

Nerve impulse transmission needs to be fast. Impulse speed is dependent on the diameter of an axon. Vertebrate evolution improved on things by adding a myelin insulating sheath.

Most of the myelin sheath is composed of lipid containing membranes-- a material ideally suited to preventing the passage of ions across the axon plasma membrane. As a result of the myelin sheath coating, action potentials can occur only in the unwrapped regions-- the nodes of Ranvier regions.

Interestingly, the action potential that occurs at one node is strong enough to trigger another action potential at the next node. This makes for a "skipping" of action impulses from one node to another rather than continuously along the axon-- something called saltatory conduction.

All of this means that nerve impulse conduction along myelinated nerves is fast-- nearly 30 times faster than impulses along unmyelinated nerve fibers of a similar diameter.

If you think this myelin material isn't important, take a look at this sidebar that discusses multiple sclerosis. Shucks, you might want to take a look at it in any event.

Neurons are linked with their target through specialized junctions called synapses. When you look carefully at the "junctions," however, you find that the neuron does not make actual contact with the target cell. The two cells are separated by a narrow gap called the synaptic cleft.

How does the signal get across the gap? The answer is: neurotransmitters-- different chemicals that are released from neurons that subsequently stimulate or inhibit the activity of a target cell.

Neurotransmitters are stored in small membrane-bound packets called synaptic vesicles. They have no effect while they remain within the neuron. When a nerve impulse reaches the end of an axon, it triggers the opening of calcium ion channels in that part of the cell's membrane and allows calcium ions to flow into the synaptic knobs. Calcium ions are potent inducers of exocytosis, the discharge of materials out of a cell.

So, the discharged neurotransmitter materials spill into the synaptic cleft, diffuse across the gap and bind specifically to receptor sites on the target cell's plasma membrane. Take a look at this diagram for a re-phrasing of all this.

Neurotransmitter interaction with a target cell causes one of two things to happen:

Either it decreases the membrane potential of the target cell which will excite the target cell, making it more likely to respond or it can increase the membrane potential of the target cell, which will inhibit the target cell, making it less likely to respond. Take a look at this diagram for an example of presynaptic inhibition.

But we're not done yet. If the story ended here, target cells would be unable to recover from a nerve impulse. This is obviously not the case. Target cells are relieved in at least two ways: by enzymes that destroy the neurotransmitter molecules and by enzymes that effect a re-uptake of neurotransmitters back into the neuron that originally released them.

The effect of given nerve impulse lasts no longer than a few milliseconds because of this neurotransmitter destruction/re-uptake.

Over 30 different neurotransmitters have been discovered. Most act within the brain alone and some such as dopamine, have dramatic effects on emotions.

Do neurons always function properly? No. Sometimes things go terribly wrong at the synapse.

Synapses are the sites of information integration. A single impulse transmitted by a single neuron seldom initiates a response in a target cell because it fails exceed the target cell's excitation threshold. Usually, activating a target cell requires a number of impulses which when added together, causes a reaction.

Our alarms would be set too sensitive if each single neuron firing an impulse would trigger a reaction. The phenomenon would be much like the car alarms you hear all too often these days, triggered it seems by someone walking by.

We'll continue with some more about the nervous system in the next module or you can return to the Syllabus Page.