PSY148: Neurotransmitters Overview & learning objectives. Human brain structure

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1 1 of /02/16 09:04 PM PSY148: Neurotransmitters Overview & learning objectives Human brain structure Sections through the brain Directional terms Directional terms in action Neuron- a cell specialized for information transmission The synapse Loewi's experiment on vagal nerve stimulation Electron microscope pictures of synapses Supplementary information References and further reading Feedback Overview: Learning objectives This lecture introduces some of the special words, phrases and concepts you will need for the course. Just like learning a foreign language - hard at first - but you will find the inhabitants of this new country have some interesting and unusual things to say about human behaviour. Loewi's experiment on vagal nerve stimulation is used to illustrate the beauty associated with the design and execution of a groundbreaking scientific discovery. identify the major brain areas visible on a mid-sagittal section of the brain describe how the brain is cut to create coronal, horizontal and sagittal sections explain the directional terms: Ventral, Dorsal, Rostral, Caudal, Lateral, Medial, Bilateral, Ipsilateral and Contralateral list the parts of a neurone describe the location of the synaptic cleft describe Loewi's experiment on vagal nerve stimulation and explain the significance of his findings describe the location of neurotransmitters and their role in neurotransmission Human brain structure

2 2 of /02/16 09:04 PM As I mentioned in class, Vesalius was a 14th century anatomist who spent a good deal of his time in graveyards and places of execution. He would then dissect the corpses and make detailed notes and illustrations. He later commissioned the artist Titan to do the illustrations for his book Di Humani Corporis Fabrica. This book and the illustrations proved revolutionary in the field of medicine and art. Vesalius's work is a nice example of how important it is to observe - and accurately report your observations - in any scientific endeavour. Vesalius' approach to anatomy is interesting from a scientist's point of view because he: gave public demonstrations of dissection ran foul of the Inquisition and was accused of human vivisection, and worse still heresy! challenged Galen's view of human anatomy on the grounds that Galen had not actually dissected any human corpses. ( Galen, who died in 203 BC, was such an influential anatomist and physiologist that research virtually ground to a halt for over a thousand years after he died. Apparently he kept at least 20 scribes to write down his every dictum - an early case of 'publish or perish'! ) Points to ponder To what extent does Vesalius' work exemplify the scientific method? How do you think religious authorities in the 14th century would have reacted to the scientific method? The next picture shows some parts of the brain that are visible if we slice the human brain in half. As you go through this course you will learn more about the function of these areas, and how they interact with each other to influence our behaviour. This diagram shows: a part of your brain where the nerves from your eyes cross over to go to the opposite side of the brain - the optic chiasm a part of the brain - stimulated by accident in early research with rats - that may be our 'pleasure centre' - the septum a area that is different in size between men and women - the corpus callosum an area once thought to be the control centre for our 'basic instincts' - the hypothalamus

3 3 of /02/16 09:04 PM Sections through the brain I said that the last picture was of a brain that had been 'sliced in half' - not a very scientific way of talking about things! There are several ways you could slice a brain in half and not end up with the view in the picture. To get around this problem, and make it clear how the brain was sliced, we need to introduce the terminology used by anatomists when they section the brain. This is an example of an operational definition - putting an operation into a form of words that can be understood by everyone. You create a coronal section when you slice bread You create a sagittal section when you cut an apple in half You create a horizontal section when you cut a bread roll to make a beefburger Here is a midsagittal section ( = a sagittal section through the midline) of rat brain from the UCLA Laboratory of NeuroImaging

4 The most important point about this picture is that the structures we explored in the human brain are also found in the brains of rats as well as other animals. This is the reason why psychologists are so interested in rats. It is obviously impossible to interfere with the human brain to understand how it works. Although we can gain valuable insight into our brain by observing the consequences of illness and accidental damage, these tragic events often involve more than one area of the brain. Animals are used because it is possible to control the extent of a lesion or area of stimulation under laboratory conditions. Some of you may be concerned with the ethical issues surrounding the use of animals in this way. Carlson (2001) puts forward the case for using animals to alleviate human suffering. More details on a rat brain atlas available over the Internet are given in the Supplementary Information section at the end of these notes Point to ponder Why do you think people bother to make detailed maps of rat brains? Directional terms Now that we have seen how to cut the brain to reveal its structures, we need to describe the way in which anatomists use general terms to describe the relative position of structures to each other. Anatomists use the following words to describe direction in the brain and other parts of the body: Direction Ventral Description Toward the front (belly) of the body or towards the bottom of the head 4 of /02/16 09:04 PM

5 Dorsal Rostral Caudal Lateral Medial Bilateral Ipsilateral Toward the back of the body, or towards the top of the head Toward the nose Toward the feet (humans) or tail Away from the midline Toward the midline On both sides of the body or head On the same side of the body or head Contralateral On the opposite side of the body or head 5 of /02/16 09:04 PM

6 6 of /02/16 09:04 PM Directional terms in action It is important to clearly distinguish between parts of the brain that are very close together - they can often have very different functions! The diagram shows the location of the lateral hypothalamus (LH) and ventromedial hypothalamus (VMH) in a coronal section of the rat brain. Notice how the names of these brain areas reflect their relative positions in the brain. Rats with LH lesions eat and drink very little Rats with VMH lesions eat enormous amounts of food and soon become obese This diagram also illustrates bilateral symmetry in the brain. Each side of the brain is a mirror image of the other side Neuron- a cell specialized for information transmission

7 7 of /02/16 09:04 PM If you were to enormously magnify the pictures of brain sections we have examined in this lecture you would eventually be able to see neurones. Neurones are brain cells that specialize in communication. The brain contains circuits of interconnected neurones that pass information between themselves. The picture of a raised hand is an easy way to remember the relationship between: dendrites cell body and axon In neurones, information passes from dendrites through the cell body and down the axon. This is easy to remember because when you pick up an object, the sensation travels from your fingers through your hand, and down your arm. Transmission of information through the neurone is an electrical process. The passage of a nerve impulse starts at a dendrite, it then travels through the cell body, down the axon to an axon terminal. Axon terminals lie close to the dendrites of neighbouring neurones. When the nerve impulse reaches an axon terminal it causes the release of a chemical ( called a neurotransmitter ) that travels across the gap (the synapse) between a terminal and the dendrite of the neighbouring neurone. Neurotransmitters stick to receptors in the neighbouring dendrite and trigger a nerve impulse that travels down the dendrite, across the cell body, down the axon etc. Our behaviour is the consequence of millions of cells talking to each other via these chemical and electrical processes. The synaptic junction between neurones

8 8 of /02/16 09:04 PM Neurotransmitters are responsible for transmitting information across the synaptic gap between neurones. Neurotransmitters are stored in synaptic vesicles. When action potentials are conducted down an axon: synaptic vesicles attach themselves to the presynaptic membrane, then break open and spill neurotransmitter into the synaptic cleft. Neurotransmitters in the synaptic cleft : attach to postsynaptic receptor sites and trigger an action potential in the postsynaptic membrane some neurotransmitter attaches to presynaptic receptors (autoreceptors) located on the membrane (pre-synaptic membrane) of the cell that originally released them 2. 'Mopping up' after information transmission This image illustrates the main events thought to be involved after transmitters have been released into the synaptic cleft. Transmitters become detached from receptors and either: diffuse through extracellular fluid (red transmitter), or undergo reuptake (blue transmitter), or are broken down by enzymes (yellow transmitter) Here is an animated version of this image Point to ponder Why do you think some neurotransmitter is broken down by enzymes and some undergoes reuptake? Loewi's experiment on vagal nerve stimulation We will now examine a groundbreaking discovery by Loewi in 1921, that shows that neurotransmission involves the release of a chemical which transmits information between neurones Donor heart

9 9 of /02/16 09:04 PM Working in 1921, Loewi knew that electrical stimulation of a frog's heart stopped heart contractions. He suspected that a chemical was released when the nerve was stimulated, because this effect persisted for a short time after the stimulation ceased. At 3a.m. one night he had a flash of insight into how he could test this idea and he went to the lab and carried out the experiment that made him famous, and demonstrated for the first time that neurotransmission involved the release of a chemical substance. In a later experiment (illustrated here) the sympathetic accelerator nerve of the donor heart was stimulated, producing increased heart rate. The donor heart released epinephrine which - a few seconds later - increased heart rate in the recipient heart. These experimental finding lies at the foundation of all modern medicines used to treat mental illness. The cardiac branch of the vagus nerve attached to a frog's donor heart was electrically stimulated, causing arrest of the heartbeat. Ringers solution perfusing the donor heart was transferred to the recipient heart. After 15 seconds, the beat in the recipient heart was also arrested. Loewi's experiment is a nice example of how important hunches are in experimental design. Point to ponder What does Loewi's experiment tell us about communication between cells in the brain? Electron microscope pictures of synapses Here are some pictures of synapses taken with an electron microscope and Eric Chudler's description of them: "Developed in the 1950's, the electron microscope can magnify objects thousands of times. Electrons are passed through an object and then recorded on film. Using the electron microscope, Dr. Pati Irish in the Department of Neurological Surgery at the University of Washington has taken these pictures of synapses. The "d" represents a dendrite and the "R" represents an axon terminal. If you look closely, you can even see some round synaptic vesicles that contain neurotransmitters. The fuzzy black areas represent the actual synapse between terminal and dendrite. The larger oval objects (there are two in the dendrite of image 1 and one in the dendrite of image 2 are 'mitochondria'. " There is a link to Eric Chudler's description of synaptic events, and pictures of synapses using the electron microscope in the Supplementary Information section at the end of this page - well worth a visit. I have written a Java applet that allows you to magnify these images so that you can examine the detail. The horizontal and vertical scroll bars enable you to move around the image. Supplementary Information

10 10 of /02/16 09:04 PM Neurotransmission Follow this link to a very good audio-visual presentation of neurotransmission Follow this link to a superb tutorial on neurotransmission created by the Dept. of Psychology, California State University. I particularly liked the fact that " The neurones of one human cerebral cortex would reach over 250,000 miles if placed end to end." One way I can relate to this massive number is to think of the miles covered by my car. It would take about 25 years of average motoring to cover this distance! Follow this link to a collection of tutorials on Basic Neural Processes. Make sure you try out the Neural Structure Quiz Here is a link to a superb description of directions and planes of section in the brain Here is a link to Eric Chudler's description of synaptic events, and pictures of synapses using the electron microscope. Well worth a visit. Brain anatomy Take a 3D tour of the brain here Follow this link to the 3D Digital map of Rat Anatomy at the UCLA Laboratory of Neuro Imaging which has labelled rat brain sections available which are useful if you want to know where structures mentioned in lectures are located Here is the authors description of their work "A three dimensional (3D) computerized map of rat brain anatomy created with digital imaging techniques is described. Six male Sprague-Dawley rats, weighing g, were used in the generation of this atlas. Their heads were frozen and closely spaced cryosectional images were digitally captured." The Sheep Brain Dissection Guide, University of Scranton NeuroscienceProgram You can view Titan's illustrations of the 14th century anatomist Vesalius' work at The Tyranny Corps Art Show You can read a description of Vesalius' life an work in the Catholic Encyclopaedia. Probe the Brain. "Beginning in the 1940s, Canadian brain surgeon Wilder Penfield mapped the brain's motor cortex -- the area that controls the movement of your body's muscles. He did this by applying mild electric currents to the exposed brains of patients while they were in surgery" The Phineas Gage Information page References and further reading Carlson, Physiology of Behavior, 7th Edition, Allyn & Bacon, Boston, If you want to know more about the chemical and electrical events surrounding neurotransmission, or the effects of drugs on these processes follow links to these topics on the SALMON home page: Transmitter release and reuptake Nerve cells and nerve impulses Electrical events and nerve impulses Depression Reserpine effects on transmitters Feedback