What are Neurons What are Neurotransmitters What Part

What are Neurons? What are Neurotransmitters? What Part Do They Play in Mental Illness? Developed by Roger F. Cram Hiram College in Hiram, Ohio 44234 Copyrighted © with all rights reserved January 2011, October 2011, July 2012 NAMI (National Alliance on Mental Illness) Portage and Geauga Counties in Ohio July 30, 2012 Although copyrighted, permission is granted for use by any NAMI organization.

Electrical signals travel from the brain along the neurons (wires) to a particular device like a muscle cell, a heart cell, lungs, eyes, ears, liver, a feeling, a thought, an emotion, a dream, etc. neurons from www. images. wellcome. co. uk Neurons in the brain - illustration. Credit: Benedict Campbell.

What do neurons look like? There are 10 billion nerve cells in the brain. Transductions – neurons – Feb. 4 th, 2010 by Wolf IMAGES FROM RESEARCH - NEURONS AND NEURONAL PROTEINS by Robert S. Mc. Neil

Dendrites: Electriccharge receivers Soma (Cell Body) Direction of electrical charge to the next neuron Axon Myelin Cell nucleus Axons: Electric charge transmitters Source: Modeling Future Heroes, A Practical Application of Heroic Values, By Roger F. Cram

How Does a Neuron Carry An Electrical Charge? Neurons attach to each other through the synapse gap (doorbell button or electric switch) carrying an electrical charge from one neuron to the other. These neurons form the “wires” or nerves carrying information throughout our body.

Often many neurons are linked together where the dendrite connects to the axon carrying electrical signals along their path. Axon Dendrite Electrical Connection Direction of current flow Source: Modeling Future Heroes, A Practical Application of Heroic Values, By Roger F. Cram

Dendrites Connected to Axons Act Like Electric Switches Allowing an Electrical Charge to Move Along a Wire SWITCH Axon Dendrite Source: Modeling Future Heroes, A Practical Application of Heroic Values, By Roger F. Cram

Involuntary Neurons are used to carry electrical signals for involuntary processes: digest your food, keep your heart beating, repair cells, clean your blood, create thoughts and emotions (fear, lust, jealousy, self-esteem), carry light images from your eyes to your brain, create hearingtouch-taste-smell, fight disease, grow a baby, create the sensation of hunger, etc….

Voluntary Neurons are also used to carry electrical signals for voluntary movements like moving muscles (running, walking, writing, working, typing, taking a bath, getting dressed, driving a car) or for thinking (solving a problem, creating art, reading a book, meditating, imagining things).

Neuron Signals • Your brain triggers six trillion electrical signals through your neurons every second to operate your body and allow you freedom of thought, movement and life. • How much is six trillion? Well, six trillion pennies stacked end-on-end, would go from the earth to the moon, 243, 000 miles, twentyfour times! • Mental illness is a disease of these electrical circuits in the brain.

The electrical signal is passed from one neuron to the next until it is either blocked or it reaches its targeted device (muscle, thought, heart beat, eye, tongue, hand, etc. ). That’s how memory works, how the entire body works, how we think, how our emotions make us aware of pleasure, panic, and sorrow; that’s how we run, speak, fight disease, heal a scratch, see, hear, taste, touch, yell at our kids – all through electrical connections going through nerves carried from one neuron to the next.

Synapse Connection (switch) Axon Connected to a Dendrite) Axon Dendrite Source: Modeling Future Heroes, A Practical Application of Heroic Values, By Roger F. Cram

What does the connection of two neurons look like? Axon end Synaptic Cleft (the gap) Electrical Connection Dendrite end The Brain Bank Your plastic brain Posted on June 20, 2011 by Brain Bank Manc

AXON TERMINAL END End of first neuron Start of next neuron Dendrite End Source: Modeling Future Heroes, A Practical Application of Heroic Values, By Roger F. Cram

The Synapse Gap Neurons, although they carry the electrical charge from one neuron to the next, are not actually touching each other, but separated by a very small gap called the “synapse cleft or gap” serving as an open switch or doorbell button. Something must happen to push the doorbell button, to throw the switch, to carry the electrical charge across this gap to the next neuron.

End of first neuron Incoming electrical charge AXON TERMINAL END Start of next neuron There is a gap or empty space between the two connecting neurons. Gap or Synaptic Cleft Dendrite Source: Modeling Future Heroes, A Practical Application of Heroic Values, By Roger F. Cram

When an electrical charge reaches the end of the first neuron at the axon, it causes vesicles, being tiny bags containing chemical neurotransmitters, to drop down and release their contents into the synapse cleft or gap. The yellow Receptor round molecules represent one of over 100 different chemicals your brain uses as neurotransmitters to carry the electrical charge across the gap to the dendrite receptors, being the next neuron. This transfer of electrical-to-chemical-to-electrical information is how the brain controls all functions necessary for life. AXON Vesicles Neurotransmitters Dendrite

Let’s take another look at this illustration. Notice the vesicles? Axon end Synaptic Cleft (the gap) Electrical Connection Dendrite end The Brain Bank Your plastic brain Posted on June 20, 2011 by Brain Bank Manc

Incoming electrical charge AXON TERMINAL END Vesicle Neurotransmitter (Serotonin) Start of next neuron Receptor Dendrite Continuation of charge to next neuron. Source: Modeling Future Heroes, A Practical Application of Heroic Values, By Roger F. Cram Source: NAMI–Family to Family Course, Class 6, Handout 2–Basic Neuro-transmission at the Synapse–page 6. 23 Paragraph 3

Neurotransmitters If the neurotransmitter (chemical making the electrical connection between two neurons) is in the part of the brain controlling the beating heart, the electrical impulses will go along the chain of neurons to the heart muscle causing it to pump. If the neurons are in the part of the brain controlling voluntary muscle control, and you are trying to wave good-bye, the electrical impulses will go along a chain of neurons to the muscle cells in the arm allowing you to wave good-bye.

Neurotransmitters If the neurons are in the part of the brain controlling emotions, and you are in a crisis situation, instinct will trigger the electrical neurotransmitter impulses resulting in the fight-or-flight response and the necessary emotions and muscle action (fighting, yelling, threatening, blocking an attack, fleeing, running, jumping out of the way, etc. ).

Neurotransmitters If the neurons are in the part of the brain controlling emotions and you are Bipolar, extra neurotransmitters may carry excessive electrical “good feeling” impulses (manic) or insufficient neurotransmitters may carry a deficient amount of “good feeling” impulses (depression) without your permission. The neurons and neurotransmitters simply take over. This is what many experts think happens with bipolar, but they’re not absolutely sure.

In the following illustration, the neurotransmitter is serotonin (yellow circle ) and it carries the electrical charge from the axon into the gap. When enough serotonin binds into the receptors of the next neuron, the electric charge will be forwarded. This communication between neurons is brief, lasting about 1 millisecond.

Incoming electrical charge AXON TERMINAL END Vesicle Neurotransmitter (Serotonin) Start of next neuron Receptor Dendrite Continuation of charge to next neuron Source: Modeling Future Heroes, A Practical Application of Heroic Values, By Roger F. Cram

The serotonin molecules are shown as round and the receptors (docking sites) that receive them are the correctly sized semi-circular dish so the round serotonin molecule fits perfectly into the receptor, thus transmitting the electric charge. Source: NAMI – Family to Family Course, Class 6, Handout 2 – Basic Neuro-transmission at the Synapse – page 6. 23 Incoming electrical charge AXON TERMINAL END Vesicle Gap or Synaptic Cleft Start of next neuron Receptor Dendrite Continuation of charge to next neuron. Source: Modeling Future Heroes, A Practical Application of Heroic Values, By Roger F. Cram

If a chemical other than the round serotonin molecule were to enter the synapse gap, assuming each molecule has a unique molecular shape, it would probably not fit into the receptor being a different shape, and therefore not transfer the electrical charge to the next neuron. Incoming electrical charge AXON TERMINAL END Neurotransmitter or chemical other than Prozac Will not fit into receptor; therefore, will not carry forward a charge. Start of next neuron Receptor Dendrite Continuation of charge to next neuron. Source: Modeling Future Heroes, A Practical Application of Heroic Values, By Roger F. Cram

Once the neurotransmitter, in this case the yellow serotonin, delivers the electrical charge to the receptors of the next neuron, its job has been completed – it has delivered its message. New messages (electrical charges) will soon be coming down from the axon in other vesicles so the “used” serotonin must leave the synapse cleft or gap so it does not interfere with the new messages.

The serotonin is released from the receptor and then removed from the gap two ways: (1) an uptake pump passes the serotonin back up into the original axon from which it came (2) a chemical enzyme metabolizes the serotonin getting rid of it. Source: NAMI – Family to Family Course, Class 6, Handout 2 – Basic Neuro-transmission at the Synapse – page 6. 23 paragraph 6

In the next illustration, notice the addition of the uptake pump. It is the correct size and shape to remove the serotonin molecule. Serotonin is removed from the gap by passing into the uptake pump and delivered back into the axon. Source: NAMI – Family to Family Course, Class 6, Handout 2 – Basic Neuro-transmission at the Synapse – page 6. 23 1) Reuptake

AXON TERMINAL END Start of next neuron Uptake Pump Dendrite Continuation of charge to next neuron. Serotonin molecules being released by the receptor after they delivered their charge. They are going to the uptake pump. Source: Modeling Future Heroes, A Practical Application of Heroic Values, By Roger F. Cram

Sometimes an enzyme, released from the axon, breaks down the serotonin molecules and removes them from the synapse cleft. This “clean-up enzyme” action, where the serotonin is metabolized (broken down) is a second way of removing a neurotransmitter from the gap serving the same purpose as the uptake pump. Source: NAMI – Family to Family Course, Class 6, Handout 2 – Basic Neuro-transmission at the Synapse – page 6. 23 2) Metabolism Entering enzyme is shaped to remove serotonin molecule from the synapse cleft area. Forward motion of enzyme. Serotonin Source: Modeling Future Heroes, A Practical Application of Heroic Values, By Roger F. Cram

AXON TERMINAL END Clean-up enzyme Serotonin being metabolized (broken down) by the enzyme. Start of next neuron Receptor Dendrite Continuation of charge to next neuron. Source: Modeling Future Heroes, A Practical Application of Heroic Values, By Roger F. Cram

Neurotransmitters and Emotions *****UNDERSTAND THIS***** In the emotional sections of the brain, the electrical charge created by neurotransmitters through the synapse gap IS our sensation and awareness of life. It is where emotions are created, felt, and realized. It is where we experience life and are aware that we exist!

Neurotransmitters These neurotransmitters (Over 100 different chemicals like dopamine and serotonin) are critical in understanding how we feel, our moods, our aggression, our stress levels, how we function, how we think, and whether or not we are in a nurturing relationship or locked in a straight jacket.

Neurotransmitters That sudden sadness you feel when hurt by some one you love is felt because of neurotransmitters. That panic you feel when suddenly frightened is felt because of neurotransmitters. “Road rage” is felt because of neurotransmitters. Are you afraid of spiders or high places? Are you bipolar and experience depression and manic episodes? Do you have panic attacks? OCD? ADHD? Yep – neurotransmitters!

Neurotransmitters If your “feel good” neurotransmitters are sufficient you will most likely experience happiness, motivation, focus, emotional stability, good feelings toward others, and calmness through difficulties.

Neurotransmitters If your “feel good” neurotransmitters are deficient you may feel depression, panic or anxiety, sleeplessness, moody periods, irritability, over aggressiveness, and stress.

Some Types of Neurotransmitters and Their Function Neurotransmitter Its Function Too Much Too Little Serotonin Mood regulation, hunger, sleep, problems with anger control, sexual desire, decreased anxiety Dopamine Motor movement and alertness/ attention, good feelings, aggression, thinking, planning Parkinson's disease Schizophrenia, lack of remorse, inability to feel love or affection Endorphins Pain control, stress reduction, feelings of pleasure, "natural opiates“ Potentially involved in addiction Sense of inadequacy, inability to combat pain Acetylcholine ACh Critical to motor movement, learning, and memory; has a part in scheduling REM (dream) sleep. Alzheimer's and muscle disorders. GABA (gammaaminobutyric acid) Brain's major inhibitory neurotransmitter, reduced anxiety, reduced insomnia Nor epinephrine "Fight or Flight, “ controls alertness, arousal, elevates heart rate, circulation, respiration, and mood elevation Depressed mood, racing Lack of energy, lack of drive, heart, manic, elevated reduced focus on goals blood pressure Glutamate Brain's major excitatory neurotransmitter, creates links between neurons that form basis of learning, long-term memory Lou Gehrig's disease Depression, obsessivecompulsive disorder, and suicide, irrational Seizures, insomnia, anxiety disorder, epilepsy, racing thoughts Over stimulation of the brain, seizures General Psychology – Neurotransmitters - Dr. C. George Boeree 2009; Healthy Botanicals

Dopamine and Serotonin Pathways in the Brain NIDA National Institute on Drug Abuse July 2008 - Addiction Science: From Molecules to Managed Care

When sufficient serotonin or dopamine or another “feeling” neurotransmitter is in the synapse cleft “the gap, ” feelings of peace and less agitation are enjoyed. When an insufficient amount is in the gap, feelings of agitation might be experienced.

If a way could be found to keep the serotonin in the cleft for longer periods of time before it is removed by the uptake pump or enzyme, then more peaceful feelings and less stress could be experienced.

Prozac and Zoloft are called “serotonin reuptake inhibitors. ” Their molecular shapes imitate the shape of the serotonin molecule. They assume the role of serotonin in the synapse cleft confusing the uptake pump or the clean-up enzyme into removing the Prozac or Zoloft instead of the serotonin; thus the serotonin stays longer in the cleft connecting to the receptors and increasing feelings of peace, self-esteem, and well being.

Notice the pink molecules. They represent the drug Prozac. Although their molecular shape is different than the yellow serotonin molecules, it is similar enough to fit into the uptake pump; therefore, when the uptake pump eliminates some of the pink molecules (Prozac) instead of the serotonin, more serotonin molecules will remain in the gap increasing connections with the receptors, passing on their charge, and creating more peaceful feelings of wellbeing. Serotonin Prozac AXON Electric Charge Uptake pump removing Prozac Entering captureenzyme Cleft Charge moving on to next neuron GAP DENDRITE

Dopamine is a neurotransmitters like serotonin playing an important role in our “reward” and “pleasure” centers and is instrumental in regulating many normal and pathological behaviors.

All anti-psychotic drugs prevent dopamine from binding to the receptors on the receiving cell neuron (dendrite). This blocks the electrical charge from going on to the next neuron, thus blocking the stressful emotion inherent in the neurotransmitter. Receptors Gap Dendrite end Source: NAMI – Family to Family Course, Class 6, Handout 2 A – Basic Neuro-transmission at the Synapse – page 6. 24 Dopamine Axon end Anti-psychotic drug entering receptors blocking dopamine from carrying the feeling charge to the next neuron. Uptake Pump removing Dopamine Axon Gap Dendrite Cleft or Gap Source: Modeling Future Heroes, A Practical Application of Heroic Values, By Roger F. Cram

Instinct and Neurotransmitters • Homo Sapiens, being us - modern-day humans - instinctually, need to feel good about themselves, to develop feelings of self-worth and accomplishment which results from endorphins, serotonin, dopamine, and other “feel good” neurotransmitters entering the “synapse gap. ” • When something occurs indicating a boost in selfworth is justified (graduating from school, winning a game or race, giving birth, completing a project, falling in love, getting public recognition for accomplishments, etc. ) endorphins and other “feel good” neurotransmitters are triggered to enter the “synapse gap” in the emotional part of the brain.

Recreational Drugs and Neurotransmitters • Unfortunately, there are easier ways to feel the wonderful sensations and euphoria created in the “synapse gap” without completing a great accomplishment. • Alcohol, marijuana, caffeine, cocaine, heroine, nicotine, and other recreational drugs increase the levels of dopamine because of their similar molecular shapes. They “fool” the uptake pump into eliminating them from the gap, thus increasing dopamine levels and the associated feelings of well being. • LSD, mescaline, and ecstasy work by attaching to serotonin receptor sites and thereby blocking emotional signals from connecting to the receptors of the next neuron. General Psychology 2009 Neurotransmitters Dr. C. George Boeree

Neurotransmitters and Feelings Humans seek pleasure and avoid pain. Feelings of pleasure and euphoria come from great accomplishments. They also come from artificial stimuli like drugs. Marijuana Dopamine Cocaine More dopamine in the gap connecting with the receptors. Charge from axon Uptake pump removing marijuana & cocaine Cleft Source: Modeling Future Heroes, A Practical Application of Heroic Values, By Roger F. Cram

Morphine reduces pain and is often given to patients in hospitals and the wounded on battle fields for this purpose. The morphine molecule has a similar shape as the neurotransmitters in the neurons transmitting pain signals, but the morphine molecule will not carry the electrical charge forward to the next neuron once it is in the receptor, thus blocking the pain signal.

Morphine Molecule – a pain reducer AXON TERMINAL END Neurotransmitter in pain-sending neuron. Start of next neuron Receptor Morphine molecule blocks pain signal - no electric charge is carried forward – thus pain is reduced Dendrite Continuation of charge to next neuron. Source: Modeling Future Heroes, A Practical Application of Heroic Values, By Roger F. Cram

Medicine Side Effects • When medicines are introduced into the human body they unfortunately do not only enter the cells and neurons associated with the illness they are trying to relieve, but other areas of the body and brain as well. • Medications designed to treat schizophrenia affect the neurons associated with that disease in the brain, but they also connect with the neurons that affect saliva regulation; thus one of the side effects of these medications is dry mouth.

Medicine Side Effects • Medicines also enter the synapse gaps of neurons that control muscles, heart rate, vision, weight gain, constipation, nervousness, anxiety, insomnia, headaches, nausea, and many others. These medications interfere with the neuron’s neurotransmitter keeping it from performing its normal function (heart rate, vision, muscle movements, etc. ) by blocking the receptors, stopping the uptake pump, stopping the metabolizing enzyme, or by having the uptake pump remove the medicine instead of the existing neurotransmitter.

Medicine Side Effects • Prolixin is a drug frequently prescribed for schizophrenia because it helps eliminate delusions and social withdraw by affecting the neurotransmitters causing the disease. • Prolixin also enters other neurons in the brain that control muscle movements (hand tremors are created), that influence the eyes (blurred vision is a side effect), and that control the heart (a rapid heart beat can result). Source: NAMI – Family to Family Course, Class 6, Handout 9 – First Generation Typical Narcoleptic Medications – page 6. 36

Prozac and Zoloft are drugs called reuptake inhibitors and they do their work in the gap by being absorbed by the uptake pump leaving more serotonin in the gap. When more serotonin is in the gap, there is more chance for stimulation by the serotonin at the receiving receptors, thus increasing feelings of wellbeing. Anti- depressant medications do not interfere with neurotransmitter transmissions across the gap like Prozac does, but instead they block the reuptake pump, thus leaving more neurotransmitters in the gap to react with the receptors of the next neuron. Anti-depressant drugs called MAO inhibitors prevent the metabolic breakdown of neurotransmitters by interfering with the removing enzyme, thus leaving more neurotransmitter in the gap. Anti-psychotic drugs block the dendrite’s receptors from carrying the charge to the next neuron, thus blocking the painful emotional signals. Source: NAMI – Family to Family Course, Class 6, Handout 2 – Basic Neuro-transmission at the Synapse – page 6. 24

AXON TERMINAL END Anti-depressant MAO inhibitors prevent the enzyme from breaking down the neurotransmitter Anti-depressant medications block the uptake pump Reuptake inhibitor drugs – Prozac & Zoloft – are absorbed by the uptake pump leaving more serotonin in the gap for the receptors Receptor Anti-psychotic drugs block the receiving receptors from carrying the charge to the next neuron Prozac Dendrite Source: NAMI–Family to Family Course, Class 6, Handout 2 A–Basic Neuro-transmission at the Synapse–page 6. 24 Source: Modeling Future Heroes, A Practical Application of Heroic Values, By Roger F. Cram

Some Diseases Involving Neurons • • • • Bipolar disorder Cerebral Palsy Parkinson’s Disease Schizophrenia Panic attacks Obsessive-compulsive disorder (OCD) Depression Epilepsy Alzheimer's Disease Attention Deficit Disorder (ADD / ADHD) Multiple Sclerosis Autism Turret's Syndrome

Brain disorders and mental illness are often caused by an over or under developed portion of the brain. Neurons misfiring, too much of a neurotransmitter, and more often, a neurotransmitter deficiency are contributing factors. An irregular brain development during adolescence is often suspected for causing mental illness or an injury or a suspicious gene deciding to fire at the beginning of puberty.

Many of the causes of mental illness and brain disorders are still a mystery with research continuing every day. But one thing is for sure, whatever the causes and treatments that are discovered, you can bet neurons and neurotransmitters will play an intricate role. Image Source Page: http: //colinfarbotko. blogspot. com/2010_04_01_archive. html

The End of this presentation… …the beginning of hope. th 2011 Picture Source: Genetic Engineering and Biotechnology News May 4

Sources of Material and Photo Credits: • NIDA National Institute on Drug Abuse July 2008 - Addiction Science: From Molecules to Managed Care • Modeling Future Heroes, a Practical Application of Heroic Values, by Roger F. Cram, book in progress • NAMI (National Alliance of Mental Illness) nami. org • NAMI – Family-to-Family Teacher’s Manual • Genetic Engineering and Biotechnology News, May 4, 2011 • neurons from www. images. wellcome. co. uk • The Brain Bank Your plastic brain Posted on June 20, 2011 by Brain Bank Manc • Neurons in the brain - illustration. Credit: Benedict Campbell • General Psychology – Neurotransmitters - Dr. C. George Boeree 2009 • Healthy Botanicals • IMAGES FROM RESEARCH - NEURONS AND NEURONAL PROTEINS by Robert S. Mc. Neil • Transductions – neurons – Feb. 4 th, 2010 by Wolf • NIDA National Institute on Drug Abuse July 2008 - Addiction Science: From Molecules to Managed Care