Neuroscience: Science of the Brain PDF

PDF Page Organizer - Foxit Software NEUROSCIENCE SCIENCE OF THE BRAIN AN INTRODUCTION FOR YOUNG STUDENTS British Neuroscience Association European Dana Alliance for the Brain  PDF Page Organizer - Foxit Softwar...

PDF Page Organizer - Foxit Software NEUROSCIENCE SCIENCE OF THE BRAIN AN INTRODUCTION FOR YOUNG STUDENTS British Neuroscience Association European Dana Alliance for the Brain  PDF Page Organizer - Foxit Software Neuroscience: the Science of the Brain 1 The Nervous System P2 2 Neurons and the Action Potential P4 3 Chemical Messengers P7 4 Drugs and the Brain P9 5 Touch and Pain P11 6 Vision P14 Inside our heads, weighing about 1.5 kg, is an astonishing living organ consisting of 7 Movement P19 billions of tiny cells. It enables us to sense the world around us, to think and to talk. The human brain is the most complex organ of the body, and arguably the most 8 The Developing P22 complex thing on earth. This booklet is an introduction for young students. Nervous System In this booklet, we describe what we know about how the brain works and how much 9 Dyslexia P25 there still is to learn. Its study involves scientists and medical doctors from many disciplines, ranging from molecular biology through to experimental psychology, as well as the disciplines of anatomy, physiology and pharmacology. Their shared 10 Plasticity P27 interest has led to a new discipline called neuroscience - the science of the brain. 11 Learning and Memory P30 The brain described in our booklet can do a lot but not everything. It has nerve cells - its building blocks - and these are connected together in networks. These 12 Stress P35 networks are in a constant state of electrical and chemical activity. The brain we describe can see and feel. It can sense pain and its chemical tricks help control the uncomfortable effects of pain. It has several areas devoted to co-ordinating our 13 The Immune System P37 movements to carry out sophisticated actions. A brain that can do these and many other things doesn’t come fully formed: it develops gradually and we describe some 14 Sleep P39 of the key genes involved. When one or more of these genes goes wrong, various conditions develop, such as dyslexia. There are similarities between how the brain 15 Brain Imaging P41 develops and the mechanisms responsible for altering the connections between nerve cells later on - a process called neuronal plasticity. Plasticity is thought to underlie learning and remembering. Our booklet’s brain can remember telephone 16 Artificial Brains and P44 numbers and what you did last Christmas. Regrettably, particularly for a brain Neural Networks that remembers family holidays, it doesn’t eat or drink. So it’s all a bit limited. But it does get stressed, as we all do, and we touch on some of the hormonal and 17 When things go wrong P47 molecular mechanisms that can lead to extreme anxiety - such as many of us feel in the run-up to examinations. That’s a time when sleep is important, so we let it have 18 Neuroethics P52 the rest it needs. Sadly, it can also become diseased and injured. New techniques, such as special electrodes that can touch the surface of cells, 19 Training and Careers P54 optical imaging, human brain scanning machines, and silicon chips containing artificial brain circuits are all changing the face of modern neuroscience. 20 Further Reading and P56 We introduce these to you and touch on some of the ethical issues and social Acknowledgements implications emerging from brain research. The Neuroscience Community at the University of Edinburgh The European Dana Alliance for the Brain To order additional copies: Online ordering: www.bna.org.uk/publications Postal: The British Neuroscience Association, c/o: The Sherrington Buildings, Ashton Street, Liverpool L68 3GE Telephone: 44 (0) 151 794 4943/5449 Fax: 44 (0) 794 5516/5517  PDF Page Organizer - Foxit Software This booklet was prepared and edited on behalf of the British Neuroscience Association and the European Dana Alliance for the Brain by Richard Morris (University of Edinburgh) and Marianne Fillenz (University of Oxford). The graphic design was by Jane Grainger (Grainger Dunsmore Design Studio, Edinburgh). We are grateful for contributions from our colleagues in the Division of Neuroscience, particularly Victoria Gill, and others in the neuroscience community in Edinburgh. We also thank members of the University Department of Physiology in Oxford, particularly Colin Blakemore, and helpful colleagues in other institutions. Their names are listed on the back page. The British Neuroscience Association (BNA) is the professional body in the United Kingdom that represents neuroscientists and is dedicated towards a better understanding of the nervous system in health and disease. Its members range from established scientists holding positions in Universities and Research Institutes through to postgraduate students. The BNA’s annual meetings, generally held in the spring, provide a forum for the presentation of the latest research. Numerous local groups around the country hold frequent seminars and these groups often organise activities with the general public such as school visits and exhibitions in local museums. See http://www.bna.org.uk/ for further information. The goal of The European Dana Alliance for the Brain (EDAB) is to inform the general public and decision makers about the importance of brain research. EDAB aims to advance knowledge about the personal and public benefits of neuroscience and to disseminate information on the brain, in health and disease, in an accessible and relevant way. Neurological and psychiatric disorders affect millions of people of all ages and make a severe impact on the national economy. To help overcome these problems, in 1997, 70 leading European neuroscientists signed a Declaration of Achievable Research Goals and made a commitment to increase awareness of brain disorders and of the importance of neuroscience. Since then, many others have been elected, representing 24 European countries. EDAB has more than 125 members. See http://www.edab.net/ for further information. Published by The British Neuroscience Association The Sherrington Buildings Ashton Street Liverpool L69 3GE UK Copyright British Neuroscience Association 2003 This book is in copyright. Subject to statutory exception and the provisions of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of The British Neuroscience Association First Published 2003 ISBN: 0-9545204--0-8 The images on this page are of neurons of the cerebral cortex visualised using special dyes inserted into the adjacent cells.  PDF Page Organizer - Foxit Software The Nervous System Neurons have an architecture that consists of a cell body and two sets of additional compartments called ‘processes’. One of these sets are called axons; their job is to transmit information from the neuron on to others to which it is connected. The other set are called dendrites - their job is to receive the information being transmitted by the axons of other neurons. Both of these processes participate in the specialised contacts called synapses (see the Chapters 2&3 on Action Potential and Chemical Messengers). Neurons are organised into complex chains and networks that are the pathways through which information in the nervous system is transmitted. The brain and spinal cord are connected to sensory receptors and muscles through long axons that make up the peripheral nerves. The spinal cord has two functions: it is the seat of simple reflexes such as the knee jerk and the rapid withdrawal of a limb from a hot object or a pinprick, as well as more complex reflexes, and it forms a highway between the body and the brain for information Human central nervous system showing the brain and travelling in both directions. spinal cord These basic structures of the nervous system are the same Basic structure in all vertebrates. What distinguishes the human brain is its large size in relation to body size. This is due to an enormous The nervous system consists of the brain, spinal cord and increase in the number of interneurons over the course of peripheral nerves. It is made up of nerve cells, called evolution, providing humans with an immeasurably wide choice neurons, and supporting cells called glial cells. of reactions to the environment. There are three main kinds of neurons. Sensory neurons are coupled to receptors specialised to detect and respond to different attributes of the internal and external Anatomy of the Brain environment. The receptors sensitive to changes in light, The brain consists of the brain stem and the cerebral sound, mechanical and chemical stimuli subserve the sensory hemispheres. modalities of vision, hearing, touch, smell and taste. When mechanical, thermal or chemical stimuli to the skin The brain stem is divided into hind-brain, mid-brain and a exceed a certain intensity, they can cause tissue damage ‘between-brain’ called the diencephalon. The hind-brain is an and a special set of receptors called nociceptors are extension of the spinal cord. It contains networks of activated; these give rise both to protective reflexes and to neurons that constitute centres for the control of vital the sensation of pain (see chapter 5 on Touch and Pain). functions such as breathing and blood pressure. Within Motor neurons, which control the activity of muscles, are these are networks of neurons whose activity controls these responsible for all forms of behaviour including speech. functions. Arising from the roof of the hind-brain is the Interposed between sensory and motor neurons are cerebellum, which plays an absolutely central role in the Interneurones. These are by far the most numerous (in the control and timing of movements (See Chapters on human brain). Interneurons mediate simple reflexes as well Movement and Dyslexia). as being responsible for the highest functions of the brain. Glial cells, long thought to have a purely The midbrain contains groups of neurons, each of which seem supporting function to the neurons, are now known to make to use predominantly a particular type of chemical an important contribution to the development of the messenger, but all of which project up to cerebral nervous system and to its function in the adult brain. hemispheres. It is thought that these can modulate the While much more numerous, they do not transmit activity of neurons in the higher centres of the brain information in the way that neurons do. 2  PDF Page Organizer - Foxit Software The human brain seen from above, below and the side. Side view of the brain showing division between the cerebral hemisphere and brain stem, an to mediate such functions as sleep, attention or reward. extension of which is the The diencephalon is divided into two very different areas cerebellum called the thalamus and the hypothalamus: The thalamus Cerebral Hemisphere relays impulses from all sensory systems to the cerebral Cerebellum cortex, which in turn sends messages back to the thalamus. Brain Stem This back-and-forward aspect of connectivity in the brain is intriguing - information doesn’t just travel one way. The hypothalamus controls functions such as eating and drinking, and it also regulates the release of hormones Cross section through involved in sexual functions. the brain showing the thalamus and hypothalamus The cerebral hemispheres consist of a core, the basal ganglia, and an extensive but thin surrounding sheet of Thalamus neurons making up the grey matter of the cerebral cortex. Hypothalamus The basal ganglia play a central role in the initiation and control of movement. (See Chapter 7 on Movement). Packed into the limited space of the skull, the cerebral cortex is thrown into folds that weave in and out to enable a much larger surface area for the sheet of neurons than would otherwise be possible. This cortical tissue is the most highly developed area of the brain in humans - four times bigger Cross section through the brain showing the than in gorillas. It is divided into a large number of discrete basal ganglia and corpus areas, each distinguishable in terms of its layers and callosum connections. The functions of many of these areas are known - such as the visual, auditory, and olfactory areas, the Cerebral Hemisphere sensory areas receiving from the skin (called the Corpus Callosum Basai Ganglia somaesthetic areas) and various motor areas. The pathways from the sensory receptors to the cortex and from cortex to the muscles cross over from one side to the other. Thus movements of the right side of the body are controlled by the left side of the cortex (and vice versa). Similarly, the left half of the body sends sensory signals to The father of modern the right hemisphere such that, for example, sounds in the neuroscience, Ramon y left ear mainly reach the right cortex. However, the two Cajal, at his microscope halves of the brain do not work in isolation - for the left and in 1890. right cerebral cortex are connected by a large fibre tract called the corpus callosum. The cerebral cortex is required for voluntary actions, language, speech and higher functions such as thinking and remembering. Many of these functions are carried out by both sides of the brain, but some are largely lateralised to one cerebral hemisphere or the other. Areas concerned with Cajal’s first pictures some of these higher functions, such as speech (which is of neurons and their dendrites. lateralised in the left hemisphere in most people), have been identified. However there is much still to be learned, particularly about such fascinating issues as consciousness, Cajal’s exquisite and so the study of the functions of the cerebral cortex is neuron drawings - one of the most exciting and active areas of research these are of the in Neuroscience. cerebellum. g Internet Links: http://science.howstuffworks.com/brain.htm http://faculty.washington.edu/chudler/neurok.html http://psych.hanover.edu/Krantz/neurotut.html 3  PDF Page Organizer - Foxit Software Neurons and the Action Potential Whether neurons are sensory or motor, big or small, they Spinal motor neuron Pyramidal cell Purkinje cell of cerebellum all have in common that their activity is both electrical and chemical. Neurons both cooperate and compete with each other in regulating the overall state of the nervous system, rather in the same way that individuals in a society cooperate and compete in decision-making processes. Chemical signals received in the dendrites from the axons that contact them are transformed into electrical signals, which add to or subtract from electrical signals from all the other synapses, thus making a decision Cell Body about whether to pass on the signal elsewhere. Electrical Cell Body potentials then travel down axons to synapses on the Cell Body Axon dendrites of the next neuron and the process repeats. Axon Axon The dynamic neuron 3 different types of Neurons As we described in the last chapter, a neuron consists of dendrites, a cell body, an axon and synaptic terminals. Inside neurons are many inner compartments. These This structure reflects its functional subdivision into consist of proteins, mostly manufactured in the cell body, receiving, integrating and transmitting compartments. that are transported along the cytoskeleton. Tiny Roughly speaking, the dendrite receives, the cell-body protuberances that stick out from the dendrites called integrates and the axons transmit - a concept called dendritic spines. These are where incoming axons make polarization because the information they process most of their connections. Proteins transported to the supposedly goes in only one direction. spines are important for creating and maintaining neuronal connectivity. These proteins are constantly turning over, Dendrites Cell Body Axon Synapse being replaced by new ones when they’ve done their job. All this activity needs fuel and there are energy factories (mitochondria) inside the cell that keep it all working. The end-points of the axons also respond to molecules called growth factors. These factors are taken up inside and then transported to the cell body where they influence the expression of neuronal genes and hence the manufacture of new proteins. These enable the neuron to grow longer dendrites or make yet other dynamic changes to its shape Receiving Integrating Transmitting or function. Information, nutrients and messengers flow to and from the cell body all the time. The key concepts of a neuron Like any structure, it has to hold together. The outer membranes of neurons, made of fatty substances, are draped around a cytoskeleton that is built up of rods of tubular and filamentous proteins that extend out into dendrites and axons alike. The structure is a bit like a canvas stretched over the tubular skeleton of a frame tent. The different parts of a neuron are in constant motion, a process of rearrangement that reflects its own activity and that of its neighbours. The dendrites change shape, sprouting new connections and withdrawing others, and the axons grow new endings as the neuron struggles to talk a bit Dendritic spines are the tiny green protuberances sticking more loudly, or a bit more softly, to others. out from the green dendrites of a neuron. This is where synapses are located. 4  PDF Page Organizer - Foxit Software Receiving and deciding The action-potential On the receiving side of the cell, the dendrites have close To communicate from one neuron to another, the neuronal contacts with incoming axons of other cells, each of which is signal has first to travel along the axon. How do neurons separated by a miniscule gap of about 20 billionths of metre. do this? A dendrite may receive contacts from one, a few, or even thousands of other neurons. These junctional spots are The answer hinges on harnessing energy locked in physical named synapses, from classical Greek words that mean “to and chemical gradients, and coupling together these forces clasp together”. Most of the synapses on cells in the in an efficient way. The axons of neurons transmit electrical cerebral cortex are located on the dendritic spines that pulses called action potentials. These travel along nerve stick out like little microphones searching for faint signals. fibres rather like a wave travelling down a skipping rope. Communication between nerve cells at these contact points This works because the axonal membrane contains ion- is referred to as synaptic transmission and it involves a channels, that can open and close to let through electrically chemical process that we will describe in the next Chapter. charged ions. Some channels let through sodium ions (Na+), When the dendrite receives one of the chemical messengers while others let through potassium ions (K+). When channels that has been fired across the gap separating it from the open, the Na+ or K+ ions flow down opposing chemical and sending axon, miniature electrical currents are set up inside electrical gradients, in and out of the cell, in response to the receiving dendritic spine. These are usually currents electrical depolarisation of the membrane. that come into the cell, called excitation, or they may be currents that move out of the cell, called inhibition. All these positive and negative waves of current are accumulated in the dendrites and they spread down to the cell body. If they don’t add up to very much activity, the currents soon die down and nothing further happens. However, if the currents add up to a value that crosses a threshold, the neuron will send a message on to other neurons. So a neuron is kind of miniature calculator - constantly adding and subtracting. What it adds and subtracts are the messages it receives from other neurons. Some synapses produce excitation, others inhibition. How these signals constitute the basis of sensation, thought and movement depends very much on the network in which the neurons are embedded. The action potential 5  PDF Page Organizer - Foxit Software When an action potential starts at the cell body, the first channels to open are Na+ channels. A pulse of sodium ions Research Frontiers flashes into the cell and a new equilibrium is established within a millisecond. In a trice, the transmembrane voltage switches by about 100 mV. It flips from an inside membrane voltage that is negative (about -70 mV) to one that is positive (about +30 mV). This switch opens K+ channels, triggering a pulse of potassium ions to flow out of the cell, almost as rapidly as the Na+ ions that flowed inwards, and this in turn causes the membrane potential to swing back again to its original negative value on the inside. The action- potential is over within less time than it takes to flick a domestic light switch on and immediately off again. Remarkably few ions traverse the cell membrane to do this, and the concentrations of Na+ and K+ ions within the cytoplasm do not change significantly during an action potential. However, in the long run, these ions are kept in balance by ion pumps whose job is to bale out excess sodium The nerve fibres above (the purple shows the axons) are ions. This happens in much the same way that a small leak in wrapped in Schwann cells (red) that insulate the electrical transmission of the nerve from its surroundings. the hull of a sailing boat can be coped with by baling out The colours are fluorescing chemicals showing a newly water with a bucket, without impairing the overall ability of discovered protein complex. Disruption of this protein the hull to withstand the pressure of the water upon which complex causes an inherited disease that leads to muscle- the boat floats. wasting. The action potential is an electrical event, albeit a complex one. Nerve fibres behave like electrical conductors (although New research is telling us about the proteins that make up they are much less efficient than insulated wires), and so an this myelin sheath. This blanket prevents the ionic currents action potential generated at one point creates another from leaking out in the wrong place but, every so often the gradient of voltage between the active and resting glial cells helpfully leave a little gap. Here the axon membranes adjacent to it. In this way, the action potential concentrates its Na+ and K+ ion channels. These clusters of is actively propelled in a wave of depolarisation that spreads ion channels function as amplifiers that boost and maintain from one end of the nerve fibre to the other. the action potential as it literally skips along the nerve. This can be very fast. In fact, in myelinated neurons, An analogy that might help you think about the conduction action-potentials can race along at 100 metres per second! of action potentials is the movement of energy along a firework sparkler after it is lit at one end. The first ignition Action potentials have the distinctive characteristic of being triggers very rapid local sparks of activity (equivalent to the all-or-nothing: they don’t vary in size, only in how often they ions flowing in and out of the axon at the location of the occur. Thus, the only way that the strength or duration of a action potential), but the overall progression of the sparkling stimulus can be encoded in a single cell is by variation of the wave spreads much more slowly. The marvellous feature of frequency of action potentials. The most efficient axons can nerve fibres is that after a very brief period of silence (the conduct action potentials at frequencies up to 1000 times refractory period) the spent membrane recovers its per second. explosive capability, readying the axon membrane for the next action potential. Much of this has been known for 50 years based on wonderful experiments conducted using the very large Alan Hodgkin and Andrew neurons and their axons that exist in certain Huxley won the Nobel Prize sea-creatures. The large size of these axons enabled for discovering the scientists to place tiny electrodes inside to measure the mechanism of transmission changing electrical voltages. Nowadays, a modern electrical of the nerve impulse. recording technique called patch-clamping is enabling They used the "giant axon" neuroscientists to study the movement of ions through of the squid in studies individual ion-channels in all sorts of neurons, and so make at the Plymouth Marine very accurate measurements of these currents in brains Biology Laboratory much more like our own. Insulating the axons In many axons, action-potentials move along reasonably well, but not very fast. In others, action potentials really do skip along the nerve. This happens because long stretches of the axon are wrapped around with a fatty, insulating blanket, made out of the stretched out glial cell membranes, called a myelin sheath. g Internet Links: http://psych.hanover.edu/Krantz/neurotut.html 6 http://www.neuro.wustl.edu/neuromuscular/  PDF Page Organizer - Foxit Software Chemical Messengers Action potentials are transmitted along axons to around the synaptic cleft. Some of these have miniature specialised regions called synapses, where the axons vacuum cleaners at the ready, called transporters, whose contact the dendrites of other neurons. These consist of job is to suck up the transmitter in the cleft. This clears the a presynaptic nerve ending, separated by a small gap from chemical messengers out of the way before the next action the postsynaptic component which is often located on a potential comes. But nothing is wasted - these glial cells dendritic spine. The electrical currents responsible for the then process the transmitter and send it back to be stored propagation of the action potential along axons cannot in the storage vesicles of the nerve endings for future use. bridge the synaptic gap. Transmission across this gap is Glial-cell housekeeping is not the only means by which accomplished by chemical messengers called neurotransmitters are cleared from the synapse. neurotransmitters. Sometimes the nerve cells pump the transmitter molecules back directly into their nerve endings. In other cases, the transmitter is broken down by other chemicals in the synaptic cleft. Messengers that open ion channels The interaction of neurotransmitters with receptors resembles that of a lock and key. The attachment of the transmitter (the key) to the receptors (the lock) generally causes the opening of an ion channel; these receptors are called ionotropic receptors (see Figure). If the ion channel Chemical transmitter packed in allows positive ions (Na+ or Ca++) to enter, the inflow of spherical bags is available for release positive current leads to excitation. This produces a swing across synaptic junctions in the membrane potential called an excitatory post-synap- tic potential (epsp). Typically, a large number of synapses converge on a neuron and, at any one moment, some are active and some are not. If the sum of these epsps reaches Storage and Release the threshold for firing an impulse, a new action potential is set up and signals are passed down the axon of the receiving Neurotransmitters are stored in tiny spherical bags called neuron, as explained in the previous chapter. synaptic vesicles in the endings of axons. There are vesicles for storage and vesicles closer to nerve endings that are ready to be released. The arrival of an action potential leads to the opening of ion-channels that let in calcium (Ca++). This activates enzymes that act on a range of presynaptic Transmitter Receptor Transmitter proteins given exotic names like “snare”, “tagmin” and “brevin” (ligand) Receptor G-protein - really good names for the characters of a recent scientific Extracellular adventure story. Neuroscientists have only just discovered Plasma Membrane that these presynaptic proteins race around tagging and Intracellular trapping others, causing the releasable synaptic vesicles to fuse with the membrane, burst open, and release the chemical messenger out of the nerve ending. Second Messenger Effector This messenger then diffuses across the 20 nanometre gap called the synaptic cleft. Synaptic vesicles reform when their membranes are swallowed back up into the nerve ending where they become refilled with neurotransmitter, for subsequent regurgitation in a continuous recycling process. Ionotropic receptors (left) have a channel through which Once it gets to the other side, which happens amazingly ions pass (such as Na+ and K+). The channel is made up of quickly – in less than a millisecond - it interacts with five sub-units arranged in a circle. Metabotropic receptors specialised molecular structures, called receptors, in the (right) do not have channels, but are coupled to G-proteins membrane of the next neuron. Glial cells are also lurking all inside the cell-membrane that can pass on the message. 7  PDF Page Organizer - Foxit Software The main excitatory neurotransmitter in the brain is ions in the membrane, as ionotropic receptors do, but glutamate. The great precision of nervous activity requires instead kick-starts intracellular second messengers into that excitation of some neurons is accompanied by action, engaging a sequence of biochemical events (see suppression of activity in other neurons. This is brought Figure). The metabolic engine of the neuron then revs up and about by inhibition. At inhibitory synapses, activation of gets going. The effects of neuromodulation include changes receptors leads to the opening of ion channels that allow the in ion channels, receptors, transporters and even the expres- inflow of negatively charged ions giving rise to a change in sion of genes. These changes are slower in onset and more membrane potential called an inhibitory post-synaptic long-lasting than those triggered by the potential (ipsp) (see Figure). This opposes membrane excitatory and inhibitory transmitters and their effects depolarisation and therefore the initiation of an action extend well beyond the synapse. Although they do not potential at the cell body of the receiving neuron. There are initiate action potentials, they have profound effects on the two inhibitory neurotransmitters – GABA and glycine. impulse traffic through neural networks. Synaptic transmission is a very rapid process: the time Identifying the messengers taken from the arrival of an action potential at a synapse to the generation of an epsp in the next neuron is very rapid - Among the many messengers acting on G-protein coupled 1/1000 of a second. Different neurons have to time their receptors are acetylcholine, dopamine and noradrenaline. delivery of glutamate on to others within a short window of Neurons that release these transmitters not only have a opportunity if the epsps in the receiving neuron are going to diverse effect on cells, but their anatomical organisation is add up to trigger a new impulse; and inhibition also has to also remarkable because they are relatively few in number but operate within the same interval to be effective in shutting their axons project widely through the brain (see Figure). things down. There are only 1600 noradrenaline neurons in the human brain, but they send axons to all parts of the brain and spinal cord. These neuromodulatory transmitters do not send out precise sensory information, but fine-tune dispersed neuronal assemblies to optimise their performance. Noradrenaline is released in response to various forms of novelty and stress and helps to organise the complex response of the individual to these challenges. Lots of networks may need to “know” that the organism is under stress. Dopamine makes certain situations rewarding for the animal, by acting on brain centres associated with positive emotional features (see Chapter 4). Acetylcholine, by contrast, likes to have it both ways. It acts on both The excitatory synaptic potential (epsp) is a shift in ionotropic and metabotropic receptors. The first membrane potential from -70 mV to a value closer to 0 mV. neurotransmitter to be discovered, it uses ionic mechanisms An inhibitory synaptic potential (ipsp) has the opposite to signal across the neuromuscular junction from motor effect. neurons to striated muscle fibres. It can also function as a neuromodulator. It does this, for example, when you want to focus attention on something - fine-tuning neurons in the brain to the task of taking in only relevant information. Messengers that modulate The hunt for the identity of the excitatory and inhibitory neurotransmitters also revealed the existence of a large number of other chemical agents released from neurons. Many of these affect neuronal mechanisms by interacting with a very different set of proteins in the membranes of neurons called metabotropic receptors. These receptors don’t contain ion channels, are not always localised in the region of the synapse and, most importantly, do not lead to the initiation of action potentials. We now think of these receptors as adjusting or modulating the vast array of chemical processes going on inside neurons, and thus the action of metabotropic receptors is called neuromodulation. Metabotropic receptors are usually found in complex particles linking the outside of the cell to enzymes inside the cell that affect cell metabolism. When a neurotransmitter is recognised and bound by a metabotropic receptor, bridging Noradrenaline cells are located in the locus coeruleus (LC). molecules called G-proteins, and other membrane-bound Axons from these cells are distributed throughout the enzymes are collectively triggered. Binding of the midbrain such as the hypothalamus (Hyp), the cerebellum (C) transmitter to a metabotropic recognition site can and cerebral cortex. be compared to an ignition key. It doesn’t open a door for g An excellent web site about synapses is at: http://synapses.mcg.edu/index.asp 8  PDF Page Organizer - Foxit Software Drugs and the Brain Many people seem to have a constant desire to alter their dependence the body and brain slowly adapt to the repeated state of consciousness using drugs. They use stimulant presence of the drug, but exactly what changes go on in the drugs to help them stay awake and dance the night away. brain remain mysteries. Although the primary sites of action Others use sedatives to calm their nerves. Or even of heroin, amphetamines, nicotine, cocaine and cannabis are substances that enable them to experience new forms of all different, these drugs share an ability to promote the consciousness and to forget the troubles of everyday life. release of the chemical messenger dopamine in certain brain All of these drugs interact in different ways with regions. Although this is not necessarily akin to triggering a neurotransmitter and other chemical messenger systems “pleasure” mechanism, it is thought that the drug-induced in the brain. In many cases, the drugs hijack natural brain release of dopamine may be an important final common systems that have to do with pleasure and reward - pathway of “pleasure” in the brain. It represents the signal psychological processes that are important in eating, that prompts a person to carry on taking the drug. drinking, sex and even learning and memory. Individual Drugs - How they work and The Path to Addiction and Dependence the hazards of taking them. Drugs that act on the brain or the blood supply of the brain Alcohol can be invaluable - such as those that relieve pain. Recreational drug use has a very different purpose, and the Alcohol acts on neurotransmitter systems in the brain to problem with it is that it can lead to abuse. The user can, all dampen down excitatory messages and promote inhibition of too easily, become dependent or even addicted. He or she neural activity. Alcohol’s action proceeds through stages of will then suffer very unpleasant physical and psychological relaxation and good humour, after one drink, through to withdrawal symptoms when they interrupt their drug habit. sleepiness and loss of consciousness. That is why the police This state of dependence can lead a user to crave the drug, are so strict about drinking and driving, and why there is so even though doing so is clearly damaging to their work, health much public support for this strict attitude. Some people and family. In extreme cases the user may be drawn into become very aggressive and even violent when they drink, and crime in order to pay for the drug. about one in ten of regular drinkers will become dependent alcoholics. Long-term alcohol use damages the body, Fortunately not everyone who takes a recreational drug especially the liver, and can cause permanent damage to the becomes dependent on it. Drugs differ in their dependence brain. Pregnant mothers who drink run the risk of having liability - ranging from high risk in the case of cocaine, heroin babies with damaged brains and low IQ’s. More than 30,000 and nicotine to lower risk in the case of alcohol, cannabis, people die every year in Britain from alcohol-related diseases. ecstasy and amphetamines. During the development of drug 76% Tobacco 32% 92% Alcohol 15% 46% Marijuana 9% Tranquilizers & 13% Prescription Drugs 9% 16% Cocaine 17% 2% Heroin 23% Percentage of people who have ever used the drug Percentage of users who became dependent 9  PDF Page Organizer - Foxit Software Cannabis smokers tend to develop lung diseases and they run the risk of developing lung cancer - although this has not yet been proved. About one in ten users may become dependent, which people who sell the drug are well aware of. Repeated heavy use is incompatible with the skill of driving and with intellectually demanding work; experiments have established that people intoxicated with cannabis are unable to carry out complex mental tasks. Although not yet proven, there is some evidence that heavy use by young people might trigger the mental illness schizophrenia (see p.51) in susceptible individuals. Amphetamines Amphetamines are man-made chemicals that include “Dexedrine”, “Speed”, and the methamphetamine derivative called “Ecstasy”. These drugs act in the brain by causing the release two naturally occurring neurotransmitters. One is dopamine - which probably explains the strong arousal and pleasurable effects of amphetamines. The other is serotonin - which is thought to account for their ability to cause a sense of well-being and a dream-like state that can include “Skull with a burning cigerette” by Vincent Van Gogh 1885. hallucinations. Dexedrine and Speed promote mainly dopamine release, Ecstasy more serotonin. The even more powerful hallucinogen d-LSD also acts on serotonin mechanisms in the brain. Amphetamines are powerful Nicotine psychostimulants and they can be dangerous - especially in overdose. Animal experiments have shown that Ecstasy can Nicotine is the active ingredient in all tobacco products. cause a prolonged, perhaps permanent reduction of Nicotine acts on brain receptors that normally recognise the serotonin cells. This might account for the “mid-week blues” neurotransmitter acetylcholine; it tends to activate natural suffered by weekend ecstasy users. Every year, dozens of alerting mechanisms in the brain. Given this, it’s not young people die after taking it. Frightening schizophrenia- surprising that smokers say that cigarettes help them like psychosis can happen after Dexedrine and Speed. You concentrate and have a soothing effect. The trouble is that might be lured into thinking that Speed could help you in an nicotine is highly addictive and many inveterate smokers exam - but don’t. It won’t. continue to smoke for no better reason than to avoid the unpleasant signs of withdrawal if they stop. The pleasure Heroin has long gone. While there appears to be no deleterious effect on the brain, tobacco smoke is extremely damaging Heroin is a man-made chemical derivative of the plant to the lungs and long-term exposure can lead to lung cancer product morphine. Like cannabis, heroin hijacks a system in and also to other lung and heart diseases. More than the brain that employs naturally occurring neurotransmit- 100,000 people die every year in Britain from smoking- ters known as endorphins. These are important in pain related diseases. control - and so drugs that copy their actions are very valuable in medicine. Heroin is injected or smoked whereupon Cannabis it causes an immediate pleasurable sensation - possibly due to an effect of endorphins on reward mechanisms. It is highly Cannabis presents us with a puzzle, for it acts on an addictive, but, as dependence develops, these pleasurable important natural system in the brain that uses neurotrans- sensations quickly subside to be replaced by an incessant mitters that are chemically very like cannabis. This system “craving”. It is a very dangerous drug that can kill in even has to do with the control of muscles and regulating pain modest overdose (it suppresses breathing reflexes). Heroin sensitivity. Used wisely, and in a medical context, cannabis has ruined many people’s lives. can be a very useful drug. Cannabis is an intoxicant which can be pleasurable and relaxing, and it can cause a dream-like Cocaine state in which one’s perception of sounds, colours and time is subtly altered. No-one seems to have died from an over- Cocaine is another plant-derived chemical which can cause dose, although some users may experience unpleasant panic intensely pleasurable sensations as well as acting as a attacks after large doses. Cannabis has been used at least powerful psychostimulant. Like the amphetamines, cocaine once by nearly half the population of Britain under the age of makes more dopamine and serotonin available in the brain. 30. Some people believe it should be legalised - and doing so However, like heroin, cocaine is a very dangerous drug. People could cut the link between supply of the drug and that of intoxicated with it, especially the smoked form called “crack”, other much more dangerous drugs. Unfortunately, as with can readily become violent and aggressive, and there is a life- nicotine, smoking is the most effective way of delivering it to threatening risk of overdose. The dependence liability is high, the body. Cannabis smoke contains much the same mixture and the costs of maintaining a cocaine habit draw many of poisons as cigerettes (and is often smoked with tobacco). users into crime. g Related Internet Sites: www.knowthescore.info, www.nida.nih.gov/Infofax/ecstasy.html, 10 www.nida.nih.gov/MarijBroch/Marijteens.html  PDF Page Organizer - Foxit Software Touch & Pain Touch is special - a handshake, a kiss, a baptism. adapt quickly and so respond best to rapidly changing inden- It provides our first contact with the world. Arrays of tations (sense of vibration and flutter), Merkel’s disk receptors throughout our bodies are tuned to different responds well to a sustained indentation of the skin (sense aspects of the somatosensory world – touch, temperature of pressure), while Ruffini endings respond to slowly changing and body position - with yet others for the sensations of indentations. pain. The power of discrimination varies across the body surface, being exquisitely sensitive at places such as the An important concept about somatosensory receptors is tips of our fingers. Active exploration is important as well, that of the receptive field. This is the area of skin over which pointing to important interactions with the motor each individual receptor responds. Pacinian corpuscles have system. Pain serves to inform and to warn us of damage to much larger receptive fields than Meissner’s corpuscles. our bodies. It has a strong emotional impact, and is Together, these and the other receptors ensure that you can subject to powerful controls within the body and brain. feel things over your entire body surface. Once they detect a stimulus, the receptors in turn send impulses along the sen- sory nerves that enter the dorsal roots of the spinal cord. The axons connecting touch receptors to the spinal cord are large myelinated fibres that convey information from the periphery towards the cerebral cortex extremely rapidly. Cold, warmth and pain are detected by thin axons with “naked” endings, which transmit more slowly. Temperature Meissner’s receptors also show adaptation (see Experiment Box). There corpuscle are relay stations for touch in the medulla and the thalamus, before projection on to the primary sensory area in Axons the cortex called the somatosensory cortex. The nerves Merkel’s cross the midline so that the right side of the body is disc represented in the left hemisphere and the left in the right. Sweat gland Ruffini end organ t An Experiment on Temperature A variety of very small Adaptation sensory receptors are embedded in the surface of your skin. Pacinian corpuscle This experiment is very simple. You need a metal rod about a metre long, such as a towel rail, and two buckets of water. One bucket should contain fairly hot water, the other with water as cold as possible. Put your left hand in one bucket and your right hand It begins in the skin in the other, and keep them there for at least a minute. Now take your hands out, dry them very Embedded in the dermal layers of the skin, beneath the quickly and hold the metal rod. The two ends of the surface, are several types of tiny receptors. Named after the rod will feel as though they are at different scientists who first identified them in the microscope, temperatures. Why? Pacinian and Meissner corpuscles, Merkel’s disks and Ruffini endings sense different aspects of touch. All these receptors have ion channels that open in response to mechanical deformation, triggering action potentials that can The input from the body is systematically “mapped” across be recorded experimentally by fine electrodes. Some amazing the somatosensory cortex to form a representation of the experiments were conducted some years ago by body surface. Some parts of the body, such as the tips of scientists who experimented on themselves, by inserting your fingers and mouth, have a high density of receptors and electrodes into their own skin to record from single sensory a correspondingly higher number of sensory nerves. nerves. From these and similar experiments in anaesthetised Areas such as our back have far fewer receptors and nerves. animals, we now know that the first two types of receptor However, in the somatosensory cortex, the packing density 11  PDF Page Organizer - Foxit Software of neurons is uniform. Consequently, the ‘map’ of the body including proprioceptive feedback on to motor neurons, and it surface in the cortex is very distorted. Sometimes called continues at all levels of the somatosensory system. the sensory homunculus, this would be a curiously distorted The primary sensory and motor cortices are right beside person if it actually existed with its complement of touch each other in the brain. receptors spread at a uniform density across the body surface. Active exploration is crucial for the sense of touch. Imagine that you are discriminating fine differences in texture, such You can test this differential sensitivity across the body as between different fabrics or grades of sandpaper. Which with the two-point discrimination test. Bend some paper of the following conditions do you think generates the finest clips into a U-shape, some with the tips 2-3 cm apart, discriminations: others much closer. Then, with a blindfold on, get a friend to touch various parts of your body with the tips of the paper Placing your finger-tips on the samples? clips. Do you feel one tip or two? Do you sometimes feel one Running your finger-tips over the samples? tip when you are actually being touched by two? Why? Having a machine run the samples over your finger-tips? The outcome of such behavioural experiments leads to questions about where in the brain the relevant sensory information is analysed. Functional brain imaging suggests that the identification of textures or of objects by touch involves different regions of cortex. Brain imaging is also starting to produce insights about cortical plasticity by revealing that the map of the body in the somatosensory area can vary with experience. For example, blind Braille readers have an increased cortical representation for the index finger used in reading, and string players an enlarged cortical representation of the fingers of the left hand. Pain Although often classed with touch as another skin sense, pain is actually a system with very different functions and a very different anatomical organisation. Its main attributes are that it is unpleasant, that it varies greatly between individuals and, surprisingly, that the information conveyed by pain receptors provides little information about the nature of the stimulus (there is little difference between the The homunculus. The image of a person is drawn across the pain due an abrasion and a nettle sting). The ancient Greeks surface of the somatosensory cortex in proportion to the regarded pain as an emotion not a sensation. number of receptors coming from that part of the body. They have a most distorted shape. Recording from single sensory fibres in animals reveals responses to stimuli that cause or merely threaten tissue damage - intense mechanical stimuli (such as pinch), intense heat, and a variety of chemical stimuli. But such experi- The exquisite power of discrimination ments tell us nothing directly about subjective experience. The ability to perceive fine detail varies greatly across Molecular biological techniques have now revealed the different parts of the body and is most highly developed in structure and characteristics of a number of nociceptors. the tips of the fingers and lips. Skin is sensitive enough to They include receptors that respond to heat above 460 C, measure a raised dot that is less than 1/100th of a to tissue acidity and - again a surprise - to the active millimetre high – provided you stroke it as in a blind person ingredient of chilli peppers. The genes for receptors reading Braille. One active area of research asks how the responding to intense mechanical stimulation have not yet different types of receptor contribute to different tasks been identified, but they must be there. Two classes of such as discriminating between textures or identifying the peripheral afferent fibres respond to noxious stimuli: shape of an object. relatively fast myelinated fibres, called Αδ fibres, and very fine, slow, non-myelinated C fibres. Both sets of nerves Touch is not just a passive sense that responds only to what enter the spinal cord, where they synapse with a series of it receives. It is also involved in the active control of neurons that project up to the cerebral cortex. They do so movement. Neurons in the motor cortex controlling the through parallel ascending pathways, one dealing with the muscles in your arm that move your fingers get sensory localisation of pain (similar to the pathway for touch), the input from touch receptors in the finger tips. How better to other responsible for the emotional aspect of pain. detect an object that is starting to slip out of your hand than via rapid communication between the sensory and motor systems? Cross-talk between sensory and motor systems begins at the first relays in the spinal cord, 12  PDF Page Organizer - Foxit Software Morphine Met-enkaphalin A number of chemical transmitters are involved including endogenous opioids such as met-enkaphalin. The pain-killer morphine acts on the same receptors at which some of the endogenous opioids act. The converse phenomenon of enhanced pain is called hyperalgesia. There is a lowering of the pain threshold, an Ascending pathways for pain from a region of the spinal increase in the intensity of pain, and sometimes both a cord (bottom) up to several areas in the brainstem and broadening of the area over which pain is felt or even pain in cortex including ACC (anterior cingulate) and the insular. the absence of noxious stimulation. This can be a major clinical problem. Hyperalgesia involves sensitisation of the peripheral receptors as well as complex phenomena at This second pathway projects to quite different areas than various levels of the ascending pain pathways. These include the somatosensory cortex, including the anterior cingulate the interaction of chemically mediated excitation and cortex and the insular cortex. In brain-imaging experiments inhibition. The hyperalgesia observed in chronic pain states using hyponosis, it has been possible to separate mere pain results from the enhancement of excitation and depression sensation from the ‘unpleasantness’ of pain. of inhibition. Much of this is due to changes in the responsiveness of the neurons that process sensory Subjects immersed their hands in painfully hot water and information. Important changes occur in the receptor were then subjected to hypnotic suggestion of increased or molecules that mediate the action of the relevant decreased pain intensity or pain unpleasantness. neurotransmitters. In spite of the great advances in our Using positron emission tomography (PET), it was found understanding of the cellular mechanisms of hyperalgesia, that during changes in experienced pain intensity there was the clinical treatment of chronic pain is still sadly activation of the somatosensory cortex, whereas the inadequate. experience of pain unpleasantness was accompanied by activation of the anterior cingulate cortex. A life without pain? Research Frontiers Given our desire to avoid sources of pain, such as the dentist, you might imagine that a life without pain would be good. Not so. For one of the key functions of pain is to enable us to learn to avoid situations that give rise to pain. Action potentials in the nociceptive nerves entering the spinal cord initiate automatic protective reflexes, such as the withdrawal reflex. They also provide the very information that guides learning to avoid dangerous or threatening situations. Traditional Chinese Medicine uses a procedure called "acupuncture" for the relief of pain. This involves fine Another key function of pain is the inhibition of activity - needles, inserted into the skin at particular positions in the the rest that allows healing to occur after tissue damage. body along what are called meridians, which are then rotated or vibrated by the person treating the patient. They Of course, in some situations, it is important that activity certainly relieve pain but, until recently, no one was very and escape reactions are not inhibited. To help cope in these sure why. situations, physiological mechanisms have evolved that can either suppress or enhance pain. The first such modulatory Forty years ago, a research laboratory was set up in China to mechanism to be discovered was the release of endogenous find out how it works. Its findings reveal that electrical analgesics. Under conditions of likely injury, such as soldiers stimulation at one frequency of vibration triggers the in battle, pain sensation is suppressed to a surprising degree release of endogenous opoiods called endorphins, such as – presumably because these substances are released. met-enkephalin, while stimulation at another frequency Animal experiments have revealed that electrical stimulation activates a system sensitive to dynorphins. This work has of brain areas such as the aqueductal gray matter causes a led to the development of an inexpensive electrical acupunc- ture machine (left) that can be used for pain relief instead of marked elevation in the pain threshold and that this is drugs. A pair of electrodes are placed at the "Heku" points mediated by a descending pathway from the midbrain to the on the hand (right), another at the site of pain. spinal cord. g Want to read more about acupuncture? Try this web site.... http://acupuncture.com/Acup/AcuInd.htm 13  PDF Page Organizer - Foxit Software Vision Humans are highly visual animals constantly using their brain, “seeing” this next image would then need another eyes to make decisions about the world. With forward person to look at it - a person inside the brain! To avoid an facing eyes like other primates, we use vision to sense infinite regression, with nothing really explained along the those many aspects of the environment that are remote way, we confront the really big problem that the visual brain from our bodies. Light is a form of electromagnetic energy has to solve - how it uses coded messages from the eyes to that enters our eyes where it acts on photoreceptors in interpret and make decisions about the visual world. the retina. This triggers processes by which neural impulses are generated and then travel through the Once focused on the retina, the 125 million photoreceptors pathways and networks of the visual brain. Separate arranged across the surface of the retina respond to the pathways to the midbrain and the cerebral cortex mediate light that hits them by generating tiny electrical potentials. different visual functions - detecting and representing These signals pass, via synapes through a network of cells in motion, shape, colour and other distinctive features the retina, in turn activating retinal ganglion cells whose of the visual world. Some but not all are accessible to axons collect together to form the optic nerve. These enter consciousness. In the cortex, neurons in a large number of the brain where they transmit action potentials to different distinctive visual areas are specialised for making different visual regions with distinct functions. kinds of visual decisions. Light on the eye Ganglion cell Light enters the eye through the pupil and is focused, by the Bipolar cell cornea and the lens, on to the retina at the back of the eye. Horizontal cell The pupil is surrounded by a pigmented iris that can expand Rods or copntract, making the pupil larger or smaller as light levels Cones vary. It is natural to suppose that the eye acts like a camera, forming an ‘image’ of the world, but this is a mislead- ing metaphor in several respects. First, there is never a Light static image because the eyes are always moving. Second, even if an image on the retina were to send an image into the Pupil Iris Cornea Optic nerve Retina Amacrine cell Lens The retina. Light passes through the fibres of the optic nerve and a network of cells (eg. bipolar cells) to land on the Retina rods and cones at the back of the retina. Much has been learned about this earliest stage of visual Fovea processing. The most numerous photoreceptors, called rods, are about 1000 times more sensitive to light than the other, Blind spot less numerous category called cones. Roughly speaking, you see at night with your rods but by day with your cones. Optic nerve There are three types of cones, sensitive to different wave- lengths of light. It is oversimplification to say it is the cones The human eye. Light entering the eye is focused by the lens simply produce colour vision - but they are vital for it. If over- onto the retina located at the back. Receptors there exposed to one colour of light, the pigments in the cones detect the energy and by a process of transduction initiate adapt and then make a lesser contribution to our perception action-potentials that travel in the optic nerve. of colour for a short while thereafter (see Experiment Box). 14  PDF Page Organizer - Foxit Software Over the past 25 years, important discoveries have been made about the process of phototransduction (the conver- sion of light into electrical signals in the rods and cones), the genetic basis of colour blindness which is due to the absence of certain visual pigments, the function of the retinal network and the presence of two different types of ganglion cells. About 90% of these cells are very small, while another 5% are large M-type or magnocellular cells. We shall see later that abnormalities in the M-Type cells may underlie certain cases of dyslexia (Chapter 9). t An Experiment on Colour Adaptation Focus on the small fixation cross (+) between the two large circles for at least 30 sec. Now transfer your gaze to the lower fixation cross. The two “yellow” The pathways from eye to brain. circles will now appear to be different colours. Can you think out why this might have happened? The visual cortex consists of a number of areas, dealing with the various aspects of the visual world such as shape, colour, movement, distance etc. These cells are arranged in columns. An important concept about visually responsive cells is that of the receptive field - the region of retina over which the cell will respond to the prefered kind of image. In V1, the first stage of cortical processing, the neurons respond best to lines or edges in a particular orientation. An important discovery was that all the neurons in any one column of cells fire to lines or edges of the same orientation, and the neighbouring column of cells fires best to a slightly different orientation, and so on across the surface of V1. This means cortical visual cells have an intrinsic organisation for interpreting the world, but it is not an organisation that is immutable. The extent to which an individual cell can be driven by activity in the left or right eye is modified by experience. As with all sensory systems the visual cortex displays what we call plasticity. David Hubel The next steps in visual processing Torsten Wiesel The optic nerve of each eye projects to the brain. The fibres of each nerve meet at a structure called the optic chiasm; Electrical recordings made from cells half of them “cross” to the other side where they join the in the visual cortex (left) by David other half from the other optic nerve that have stayed Hubel and Torsten Wiesel (above) have “uncrossed”. Together these bundles of fibres form the optic revealed some amazing properties. tracts, now containing fibres from both eyes, which now These include orientation selectivity, the beautiful columnar organisation of project (via a synaptic relay in a structure called the lateral such cells (below) and the plasticity geniculate nucleus) to the cerebral cortex. It is here that of the system. These discoveries led internal “representations” of visual space around us are to the award of the Nobel Prize. created. In a similar way to touch (previous Chapter), the left-hand side of the visual world is in the right-hemisphere and the right-hand side in the left-hemisphere. This neural representation has inputs from each eye and so the cells in the visual areas at the back of the brain (called area V1, V2 etc.) can fire in response to an image in either eye. This is called binocularity. 15  PDF Page Organizer - Foxit Software Research Frontiers Just black and white dots? It is at first hard Can you see if you are blind? Surely not. However, the to identify to edges or discovery of multiple visual areas in the brain has shown surfaces of the image. that some visual abilities occur without conscious But once you know it is a awareness. Certain people who have sustained damage to Dalmation dog, the image the primary visual cortex (V1) report being unable to see “pops out”. The visual things in their field of view but, when asked to reach for the brain uses internal things they claim they cannot see, they do so with knowledge to interpret remarkable accuracy. This curious but fascinating the sensory scene. phenomenon is known as “blindsight”. This is probably mediated by parallel connections from the eyes to other parts of the cortex. Being unaware of things one sees is an everyday others can be simple and automatic. Even the simplest phenomenon in normal people too. If you chat with a decisions involve an interplay between sensory input and passenger whilst driving your car, your conscious awareness may be directed entirely to the conversation - existing knowledge. yet you drive effectively, stopping at lights and avoiding obstacles. This ability reflects a kind of functional One way to try to understand the neural basis of decision- blindsight. making would be to let an individual go about their normal daily activity and record the activity of neurons as they do various things. We might imagine being able to record, with The intricate circuitry of the visual cortex is one of the great millisecond precision, the activity of every single one of the puzzles that has preoccupied neuroscientists. Different 1011 neurons of the brain. We would then have not only a lot types of neurons are arranged across the six cortical layers, of data, but also a formidable task in processing it all. We connected together in very precise local circuits that we are would have an even greater problem in interpreting it. To only now starting to understand. Some of their connections understand why, think for a moment about the different are excitatory and some inhibitory. Certain neuroscientists reasons why people do things. A person we see walking to a have suggested there is a canonical cortical microcircuit - railway station may be going there to catch a train, to meet like chips in a computer. Not everyone agrees. We now think someone off a train, or even to go “train-spotting”. Without the circuitry in one visual area has many similarities to that knowing what their intentions are, it might prove very in another, but there could be subtle differences that reflect difficult to interpret the correlations between any patterns the different ways in which each bit of the visual brain inter- of activation in their brain and their behaviour. prets different aspects of the visual world. Study of visual illusions has also given us insight into the kind of processing Experimental neuroscientists like, therefore, to bring that may be going on at different stages of visual analysis. behavioural situations under precise experimental control. This can be achieved by setting a specific task, ensuring that the human subjects are doing it to the best of their ability after extensive practice, and then monitoring their performance. The best kind of task is one that is sufficiently complex to be interesting, yet sufficiently simple to offer a chance of being able to analyse what is going on. A good example is the process of making a visual decision about the appearance of stimuli - often no more than two stimuli - with the response being a simple choice (e.g. which spot of light is bigger, or brighter?). Although such a task is simple, it does The tiles of this famous café wall in Bristol (left) are incorporate a complete cycle of decision-making. Sensory actually rectangular - but they don’t look it. The tiling arrangement creates an illusion caused by complex information is acquired and analysed; there are correct and excitatory and inhibitory interactions amongst neurons incorrect answers for the decision made; and rewards can be processing lines and edges. The Kanizsa Triangle (right) assigned according to whether performance was correct or doesn’t really exist - but this doesn’t stop you seeing it! not. This sort of research is a kind of “physics of vision”. Your visual system “decides” that a white triangle is on top of the other objects in the scene. Decisions about motion and colour A subject of great current interest is how neurons are Decision and Indecision involved in making decisions about visual motion. Whether or not an object is moving, and in which direction, are critically A key function of the cerebral cortex is its ability to form and important judgements for humans and other animals. act upon sensory information received from many sources. Relative movement generally indicates that an object is Decision making is a critical part of this capability. This is different from other nearby objects. The regions of the the thinking, knowledge-based, or “cognitive” part of the visual brain involved in processing motion information can be process. Available sensory evidence must be weighed up and identified as distinct anatomical regions by examining the choices made (such as to act or refrain from acting) on the patterns of connections between brain areas, by using best evidence that can be obtained at that time. Some human brain imaging techniques (Chapter 14), and by record- decisions are complex and require extended thinking while ing the activity of individual neurons in non-human animals. 16  PDF Page Organizer - Foxit Software A B C D Motion sensitivity. A. A side-view of the a monkey’s brain with the primary visual cortex (V1) at the left and an area called MT (sometimes called V5) in which motion-sensitive neurons are found. B. A motion-sensitive neuron in which action potentials (vertical red lines) occur frequently in response to motion in the northwest direction, but rarely in the opposite direction. Different columns of cells in MT (or V5) code for different directions of movement. C. A circular TV screen used in experiments on motion sensitivity in which dots move about in rand