Neurons, How They Communicate With One Another,

And How Drugs Affect That Communication Process

 

Revised 2/15/2003

 

Neurons (nerve cells) receive and send signals to one another.  Sensory neurons receive information from the outside world (light, sound), motor neurons convey messages to the muscles to move, and inter-neurons receive messages from and send messages to other neurons.  All behavior and thought involves neurons sending signals to one another (and to muscles) and receiving signals from one another.  As you are reading this, neurons in your eyes are responding to the light coming from the computer screen (or paper, if you printed this out).  They convey this message to the visual areas of your brain.  That area of your brain conveys the messages to….[and so on].

 

What are the different parts of the neuron and what do they do?

 

The cell body of a neuron is called the soma.  It contains mitochondria and other structures necessary for the cell to survive.  Extending from the soma are the dendrites and the axon.  The dendrites receive signals.  If the neuron is a sensory neuron, then the dendrites are specialized for receiving sensory information (light, sound).  If the neuron is a motor neuron or an inter-neuron, then the dendrites are specialized for receiving information from other neurons.

 

The axon is responsible for sending signals.  The axon is covered by the myelin sheath, a layer of fatty substance that serves as insulation.  Axons can be very long, extending all the way down your spinal cord.  It has always been hard for me to comprehend a single cell being several feet long.  I read once that the axon of a giraffe is several yards long.  In fact, the cell body and axon of the giraffe neuron that extends down the giraffe’s spinal cord is analogous to a basketball at one end of Manhattan Island, with attached rope extending down the length of the island!  Nerves are large bundles of axons traveling throughout the body.

 

Why would the axon need to be insulated by the myelin sheath? 

 

This is because the signals that a neuron sends down the axon are electrical (actually electro-chemical) in nature.  Multiple sclerosis results when the myelin sheath begins to disappear.

 

How does a nerve cell send an electrical message? 

 

Well, when at rest the neuron has an electrical charge of –70 millivolts.  How is this so?  This is because the neuron is surrounded by positively charged ions (mostly sodium), and contains negatively charged ions.

 

When a neuron sends a signal (“fires” is the term I use a lot in class), positive ions enter the neuron.  The charge rapidly changes to +50 millivolts.  The term for this change in electrical charge is called the action potential.  This charge travels down the end of the axon.

When this signal reaches the end of the axon it comes to the terminal button(s) (See figure to the left).  When the signal reaches the terminal button, vesicles in the terminal button release neurotransmitter substance into the synapse (See figure below).  A synapse is the small space between the terminal button and the cell (muscle or another neuron) that receives the signal.  

 

 

 

 

 

 

 

 

 

 

The neurotransmitter substance crosses the synapse and conveys the message to the receiving cell by briefly connecting to receptor sites on the receiving cell.

 

Are there different kinds of signals that neurons send to one another?

 

Neurons may send either excitatory signals or inhibitory signals to one another.  An excitatory signal is a message that tells the receiving neuron to “fire.”  An inhibitory signal is a message that tells the receiving neuron not to “fire.” 

For example, suppose that you are carrying a hot pan containing a cake and that you don’t want to drop it.  When the sensory neurons in your skin detect the heat, they send messages to inter-neurons in the spinal cord.  These inter-neurons convey their messages to motor neurons nearby.  Those motor neurons convey excitatory messages to the muscles in your hand, telling those muscles to move (“drop the cake!”).  This sensory-inter-motor neuron circuit is what controls reflexes.  A reflex does not require the involvement of any brain neurons – no thinking is required. 

 

In the example to the right, neuron C receives signals from neurons A and B.  Neuron A is an excitatory neuron.  Neuron B is an inhibitory neuron.  If neuron C receives a signal from A, it is more likely to “fire.”  If it receives a signal from B, it is less likely to “fire.”  Should it receive signals from both A and B, the two signals will probably cancel one another out.

 

So, the motor neuron sends an excitatory message to your muscles to move.  But you don’t drop the cake.  Why?  You hold the cake because your brain is telling your muscles to hold onto the cake by sending an inhibitory message down the spinal cord.  The inhibitory message cancels the excitatory message.

 

Neurons either send signals or they don’t (the “all-or-none law”).  The signal is always +50 millivolts.  There is never a weak signal (less than +50 mv) or strong signal (greater than +50 mv).  The signal is always +50mv.

 

Then how do we tell the difference between a touch and a paper cut?

 

While neurons always send the same signal, the number of signals a neuron may send in a single second varies a lot.  A paper cut may cause a neuron to send 500 or 600 signals per second to the brain.  A tickling sensation may be only 100 or 200 signals per second.  So, while neurons always send the same signal, the frequency of that signal will vary. 

 

Are there different kinds of neurotransmitters?

 

Yes, there are.  Acetylcholine is used by the neurons that control your muscles, heart, and lungs.  It is also used by many neurons in the brain that are involved in memory.  Alzheimer’s disease results when these acetylcholine-using neurons in the brain die.

 

Gamma amino-butric acid (GABA) is the nervous system’s major inhibitory neurotransmitter.  Thus, it is not surprising that drugs like valium affect the GABA system.  Strychnine poison also affects the GABA system.  GABA is involved in anxiety in addition to inhibition.

 

Dopamine is found in several regions of the brain.  In one region dopamine is involved in the control of movement.  When these neurons start to die, Parkinson’s disease results.  In another region of the brain, dopamine is involved in the experience of pleasure.  Cocaine affects these neurons.

 

Serotonin, found in the brain, is involved in sleep, arousal, and mood.  Many anti-depressant medications (e.g., Paxil, Prozac, Zoloft) affect the neurons that send messages via serotonin.

 

There are others, as these are just a few examples.

 

How do some drugs and some poisons affect this process?

 

There are many ways drugs affect this process.  The venom of a black widow spider, for example, causes large amounts of acetycholine to be released.  Botulism prevents acetylcholine from being released.  Nicotine directly stimulates acetylcholine receptors.  Drugs that increase the stimulation of receptor sites are known as agonists.  Drugs that decrease stimulation of receptor sites are known as antagonists. 

 

Many of these drugs and poisons are able to affect our behavior because they closely resemble the neurotransmitters themselves.  Notice the chemical similarity between the neurotransmitter dopamine and amphetamine and methamphetamine (graph to the right). 

 

We’ll say more about all of this later, but first let’s talk about how nerve signals are terminated.

 

Why should a nerve signal be terminated?

 

When your brain tells your fingers to extend, acetylcholine is released from terminal buttons into synapses between the terminal buttons and the muscles in your fingers.  The acetylcholine crosses the synapses and tells the muscles to extend by stimulating the receptor sites on the muscles.  If the acetylcholine remained in the synapses, your fingers would continue to extend.  They would stay extended, and you would not be able to then flex your fingers.  So, in order to perform more movements, that message to extend must be terminated and it must be done quickly.

 

How are nerve signals terminated?

 

There are two ways that nerve signals are terminated.  The first is that the neurotransmitter is taken back up into the terminal button.  This is called “reuptake.”  The second is that the neurotransmitter is broken down by a special chemical that exists just for that purpose.  For example, acetylcholine is rapidly broken down by a chemical called acetylcholinesterase.  Of course, the acetylcholine first has time to stimulate the receptor sites.

 

Back to drugs and poisons.  Have you ever looked at the fine print on a bottle of Prozac, Paxil, or Zoloft?  It says in there that the drug is a “selective serotonin reuptake inhibitor” (SSRI).  So, how do you think that these drugs exert their actions?  They prevent serotonin from being taken back up into the terminal buttons. 

 

These drugs are used to treat depression.  Depression might be viewed as a “slowing” of the brain.  Fewer signals are sent between all the different neurons in the brain.  The SSRI’s work by preventing serotonin reuptake from occurring.  Thus, more serotonin will be in the synapses.  With more serotonin in the synapses, the receptor sites on neurons receive more stimulation, and the brain gradually speeds up.

 

How does bug spray work?

 

Ah yes, my favorite class example.  Have you ever read the fine print on a can of insecticide?  For some of them, it says that the active ingredient is an “acetylcholinesterase inhibitor.”  Recall that acetylcholinesterase is the chemical that breaks down acetylcholine and that acetylcholine is the neurotransmitter used by the neurons that move your muscles.

 

So, the bug is moving along.  As it moves, neurons in its brain tell its legs to move forward and backward, propelling the bug along.  Then, you come along and spray it.  The active ingredients of the bug spray slowly begin to enter the bug’s body.

 

The bug will extend its leg forward.  One set of neurons conveys this message to the bug’s leg, using acetylcholine to do so.  In order to then move its leg back, the signal to move forward must be terminated.  Another set of neurons then conveys a message to the bug’s leg to move back, also using acetylcholine to do so.  Each time, acetylcholinesterase terminates the signals by breaking down the acetylcholine in the synapses.

 

However, the “acetylcholinesterase inhibitor” will prevent acetylcholinesterase from doing this.  It takes more and more time for the signals to be terminated.  The bug’s movements begin to slow.  Eventually, the signals are only partially terminated because not all of the acetylcholine is being broken down.  So, when the bug tries to move its arm back, the signal to move forward is not totally terminated.  Then, after moving its arm back the bug tries to move the arm forward.  However, the signal to move back isn’t totally terminated either.  The result is that opposite signals – to move arms forward and move arms back – are working against each other.  The bug by now is moving in a jerking fashion.  Eventually, the bug will roll over and twitch, as the acetylcholinesterase has been completely shut off, and the signals to move forward and backward are totally working against each other.

 

The Lock and Key Model

 

The way receptor sites and neurotransmitters work together has been described as a lock and a key (“lock and key model”).  The neurotransmitter (the key) fits the receptor site (the lock).  Some drugs act just like the key and attach to the receptor site, conveying a signal just like the neurotransmitter (e.g., nicotine).  Other chemicals attach themselves to receptor sites but do not convey a message (e.g., the curare poison).  This prevents the neurotransmitter itself from conveying the signal and is like a key that fits a lock but does not actually turn the lock, blocking the real key instead.

 

 

Some Examples

 

 

Schizophrenia, Parkinson’s, and Cocaine

 

Let’s finish with an example that incorporates and puts together several of the things we’ve talked about.  We’ll use an example that includes one type of schizophrenia, Parkinson’s disease, and even cocaine.

 

Let’s start with “positive-type” schizophrenia.  Positive-type schizophrenia involves “psychotic symptoms” such as delusions and hallucinations.  Delusions are false beliefs, such as the belief that one is the president and has special powers.  Sometimes this type of schizophrenia is called “paranoid” schizophrenia, because the person who has this often has paranoid thoughts.  Hallucinations include seeing and hearing things that are not real.  Positive-type schizophrenia is accompanied by an imbalance of the neurotransmitter dopamine in the brain.  More specifically, someone with positive-type schizophrenia has too much dopamine in areas of their brain involved in thought.

 

By the way, cocaine prevents dopamine reuptake.  So, when somebody snorts some cocaine, the amount of dopamine in the synapses where dopamine is used increases.  Since dopamine is involved in the “pleasure” regions of the brain (e.g., the regions that are activated by sex and chocolate, among other things), cocaine makes one feel good because the dopamine used to stimulate the receptor sites in their pleasure centers increases.

 

However, what happens when somebody uses a lot of cocaine?  Many of them begin to become paranoid.  They may have delusions.  This is called “cocaine psychosis.”  Psychiatrists say that it is almost impossible to tell the difference between paranoid schizophrenia and cocaine psychosis.  This is not surprising.  Paranoid schizophrenia is a disease in which there is too much dopamine in synapses in certain areas of the brain.  Cocaine use results in too much dopamine in brain synapses.  The causes of these two things may be different, but the results are almost the same.  One is due to a disease, and the other is due to a drug.

 

So, one remedy for the symptoms of positive schizophrenia would be to find a drug that would reduce the dopamine chemical imbalance.  Such drugs are called “anti-psychotic drugs” and we’ll talk more about them later in the semester.  One example, reserpine, reduces dopamine by destroying dopamine-containing vesicles in the terminal button.  Anti-psychotic drugs are effective at reducing psychotic symptoms.

 

In another region of the brain dopamine is involved in movement.  As we stated earlier, when these dopamine-using neurons start to die, Parkinson’s disease results.

 

Well, it so happens that some anti-psychotic drugs reduce dopamine in these movement areas in addition to the areas where the chemical imbalance existed.  In other words, we want to reduce dopamine in one area, because the chemical imbalance was only in one area.  However, the drug causes dopamine in several areas to be reduced.  The psychotic symptoms are reduced.  However, now we have a shortage of dopamine in the areas of the brain involved in movement.  What do you think this shortage would cause?

 

If you guessed that it would produce symptoms like Parkinson’s disease, you are correct.  Many drug side effects are the result of the fact that while the drug may treat the area of the body that has a problem, they also “treat” areas of the body that do not have a problem and don’t need any treatment.  For the anti-psychotic drugs that produce these movement side effects, the side effects are referred to as “tardive dyskinesia.”  Tardive dyskinesia resembles Parkinson’s disease.  This is no surprise.  Both involve a shortage of dopamine in areas of the brain involved in movement.  One is due to a disease, and the other is due to a drug.

 

Note: Text and graphics by J.K.Palmer

Copyright © 2003 Eastern Kentucky University