lecture 10 - cognition and chemicals

Question 1

The brain - what is it made of?

Answer 1

neurone that have a body, dendrites (helps them recieve info than other neuron’s), axon (some neuron’s are short to next neuron or cortex and some are long so across the whole brain)

Camillo Golgi (1843-1926)

Santiago Ramon y Cajal (1952-1934)

Question 2

The brain - neurons

Answer 2

10-100 billion neurones - do our data communication
~1000,000,000,000,000 synapses!
(each neuron has several thousand!)
KEY CONCEPT 1: Information processing is all about neural communication
KEY CONCEPT 2: Drugs affect neurotransmission
KEY CONCEPT 3: Networks learn: e.g. down-regulation.
KEY QUESTION: Is there a clear distinction between a medical/physical problem and “its all in the mind”?

Question 3

A “brain cell” or neuron

Answer 3

diagram - schematic of a neuron

action potential travels down the axon - threshold -55mv

sodium ions + and cl- ions

resting potential is -70mv

action potential occurs when charged ions flow in or out across neuron’s membrane through channels : chloride (negative); sodium, potassium, calcium (positive)

Question 4

the next neuron

Answer 4

when action potential reaches synapse it releases neurotransmitters

IPSP - inhibitory postsynaptic potential - have a negative effect so try make neurone more negative - try to stop neurone being active

EPSP - excitatory postsynaptic potential - after synapse. has a positive effect on the neurone so makes it more positively charged inside - trying to make neuron active

Question 5

Post-synaptic responses are not “all or nothing

Answer 5

neural integration
diagram
if several excitatory synapses are active at the same time, the EPSPs they produce summate as they travel toward the axon and the axon fires. if several inhibitory synapses are active at the same time, the IPSPs they produce diminish the size of the EPSPs and prevent the axon from firing.

the neuron is an ‘adding machine’.
if excitatory potentials outweigh inhibitory ones it will be active but if inhibitory ones outweigh excitatory ones it will stay silent.

each neurone can have up to thousands of synapses on it.

Question 6

Neuro-transmitter systems- the chemical brothers

Answer 6

Glutamate: Excitatory; sensory input / motor output - found everywhere in brain and spine
GABA: Inhibitory: (reduced in epilepsy; affected by many things, including alcohol) - everywhere in the brain
Dopamine: “Modulatory”. Pleasure / reward.
Serotonin: “Modulatory”. General well being. (anti-depressants) - both can be excitatory or inhibitory
Adrenalin / nor-adrenalin: Body brain communication; flight/fight Response

Question 7

dopaminergic projections

Answer 7

in frontal lobe and sub cortex

dopamine system is affected in Parkinson disease

mesocortical pathway projects to the frontal cortex

mesolimbic pathways projects to the limbic striatum

Question 8

serotonin projections

Answer 8

raphe projects throughout the cortex

also in sub cortex

Question 9

what can drugs do?

Answer 9

neurotransmitters are stored in vesicles and bind to receptors and cause as electrical charger action potential to either flow in or out of the next neurone - Na +, Cl -, K +

after neurotransmitter either bounces out into the extracellular space or gets taken cal into the cell by a reuptake transporter - a pump and shuts the synapse down. a lot of drugs target the reuptake system as if its bio cued the neurotransmitters is in the synapse for longer making it more powerful, or inhibited also means more neurotransmitters escapes

if you add receptors more responsive - more effective synapse

if you block receptors - less responsive

Question 10

General concepts:

Answer 10

Agonist: - helping inhibition
Enhances neurotranmission - effect is larger
Antagonist:
Reduces neurotranmission - less effective synapse
e.g. Benzodiazepines help epilepsy by enhancing the effect of GABA: they are….
GABA agonists - overall have an inhibitory effect
e.g. SSRIs (selective Serotonin reuptake inhibitors) are…..
serotonin agonists
Anti-depressants: e.g. Prozac, block reuptake of 5-HT / serotonin.inhibit pump that pumps serotonin out of synapse so stays in synapse and effect on neuron is stronger

Alcohol: GABA agonist (+ complex non-specific effect acting on many bodily tissues). - enhances GABA system - sleepy effects of alcohol - also dehydrates cells

Nicotine: Activates a class of acetyl choline receptors. Activates sympathetic nervous system.
Cocaine: Cocaine blocks reuptake of dopamine into synaptic terminals. Also serotonin and noradrenalin
Amphetamines: Also dopamine, serotonin and noradrenalin
Opiates: (heroin & morphine): Opiate receptors in limbic system led to discovery of “endogenous” opiates endorphins and enkaphalins. - act on endorphins

Question 11

Opioids and pain

Answer 11

Opioids regulate some networks (e.g. here it regulates glutamate pain transmission, reducing pain)

1 - substance P along with glutamate and other pain producing neurotransmitters produce depolarisation potential in pain neuron. glutamate binds to the receptors and has a positive effect.

2- opioid peptides (including morphine - has a negative effect on both sides) and opiod drugs one ligand gated K+ channels to decrease the intensity of depolarisation. it allows potassium to escape. makes it more difficult for more action potentials. takes longer for glutamate to build up positive charge so action potential happens.

depolarisation - allows action potential to happens

ligand - something that binds to a receptor as anything that binds to a protein is called a ligand.

3 - opioid receptors on sensory neurone when stimulated open Cl - ion channel and block Ca +2 channel to inhibit firing of sensory neuron.

(Don’t worry about substance P or which exact ions are involved, just take home the concept of regulating the pain transmission).

Question 12

how drugs and opiates have long term effects

Answer 12

Down-regulation
Example 1 - inhibitory auto-receptors (do not try to learn the other details) auto = self

diagram

auto-receptors shut themselves down - so when serotonin gets revealed it affects the next cell and also affects receptors on the same cell that just released the serotonin and shuts itself down. the same cell that releases serotonin also gets shut down by serotonin. it helps you keep things under control and efficient info transfer.

gives brain balance as if too much serotonin

why effects of SSRIs don’t have full effects immediately

this is where long-term learning can happen

Question 13

effect of SSRI on somatodendritic region

Answer 13

before SSRI - serotonin that escaped from synaptic bound to autoreceptors and shut the cell down. need a lot of auto receptors. this cell is more sensitive to serotonin.

after SSRI - causes increase in the somatodendritic area of the serotonin neuron and down regulation of 5HT1A auto receptors
new state of balance - inhibits cell still

Question 14

Down-regulation, example 2

Answer 14

opioids (just take home the concept of downregulation)
Opioids regulate some networks (eg here it regulates glutamate pain transmission, reducing pain)

Question 15

Here it regulates a reward pathway, increasing reward - diagram

Answer 15

short term enhancing of the reward pathway

1 - opioid drug inhibit GABA mediated inhibitory control over serotonin and dopamine neuronal firing to increase release in the terminal regions

2 - greater release of serotonin in the prefrontal cortex releases glutamate from the inhibitory influence of GABA

3- excitatory glutamate input produces an extra increase in dopamine neuronal firing to facilitate reward perception

But… the reward pathway adapts (learns) in this new opioid-rich environment, and downregulates itself, so that reward signalling now relies on the presence of the opioid… (otherwise the GABA inhibition is now too strong)

Question 16

reward pathway

Answer 16

1 - GABA inhibition increases
2 - reward pathway down-regulated

the constant inhibitions learned so down regulate there sensitivity

the circuit relies on the opioid being there otherwise it can’t work at all. relies on opioid to kill activity in the GABA cells otherwise the GABA cells are going to kill the activity in the serotonin and dopamine cells - this transition happens during addiction. systems can’t signal a reward at all unless opioid is present.

Question 17

need to know

Answer 17

• action potentials are produced when the cell is depolarised - negative to positive state - done through positive and negative ions travelling in and out of the neuron
• EPSPs and IPSPs
• neurotransmitters - bind to a protein and let ions travel in and out - ion channel
• neurotransmitter released on action potential and binds to a receptor and allows ions to come in and out
• agonist and antagonist
• reuptake and importance of autoreceptors
• all layers of cortex are regulated by GABA inhibitory neurons

Question 18

Drug addiction
How? Why?

Answer 18

lots of addictive things affect the dopamine system. why - associative issue in learning system
Cocaine, Heroine, Nicotine, Alcohol and other addictive drugs modulate activity in the dopamine reward (“pleasure”) network
Is addiction and withdrawal then a “physical phenomenon”?
Physiological withdrawal symptoms are not as severe / unpleasant as popularly imagined
Addicts often relapse following periods of abstinence
Tolerance and sensitisation effects, as well as relapse and craving are very context dependent

Question 19

drug addiction

Answer 19

associative learning plays a key role —-> so is it mainly psychological?

But dopamine plays a key role in associative learning

So “psychological” processes of addiction may have a neurochemical basis (dopamine, endogenous opiates).

Is this surprising? All “psychological” processes rely on neurotransmission of course
–> Physical / psychological dichotomy doesn’t work

so drugs that affect dopamine also affect your associative learning system

neurons - adding machines that pool and sum up all the positive and negative inputs they receive

Question 20

the nervous system

Answer 20

• The brain contains an estimated 10 to 100 billion nerve cells and about as many supporting cells, which take care of important support and ‘housekeeping’ functions.
  
  • The brain contains many different types of nerve cell which differ in shape, size and the kinds of chemicals they produce. There seem to be differences between men and women: men’s brains are approximately 150 g heavier; the number of neurons in women has been estimated to be 19 × 109, and in men the number of neurons is 23 × 109 (Walloe et al, 2014).
  • The density of neurons (brain cells) does not seem to differ significantly between the sexes but sex and age determine the total number of neurons. We lose around 9 per cent of our neurons from 18 to 93 years old – around 85,000 a day.
  • Nerve cells of the brain are organised in modules – clusters of nerve cells that communicate with each other – but individual modules do not stand alone. They are connected to other neural circuits, receiving information from some of them, processing this information and sending the results on to other modules.
    In his famous book The Modularity of Mind, the philosopher Fodor (1983) argues that modules have particular functions – just as the transistors, resistors and capacitors in a computer chip do – and are relatively independent of each other. Although this idea – modularity – is still controversial, the evidence broadly supports some degree of modularity in the brain. The aim of psychobiology and neuroscience is to understand how individual nerve cells work, how they connect with each other to form modules, and just what these modules do.

Question 21

Central nervous system - 1

Answer 21

• The brain has two primary functions: the control of behaviour and the regulation of the body’s physiological processes.
  
  • The brain cannot act alone; it needs to receive information from the body’s sense receptors and it must be connected with the muscles and glands of the body if it is to affect behaviour and physiological processes.
  • The spinal cord is a long, thin collection of nerve cells attached to the base of the brain and running the length of the spinal colum). It contains circuits of nerve cells that control some simple reflexes, such as automatically pulling away from a painfully hot object.
  • The CNS communicates with the rest of the body through the nerves – bundles of fibres that transmit information in and out of the CNS. The nerves, which are attached to the spinal cord and to the base of the brain, make up the peripheral nervous system.
  • The human brain has three major parts: the brain stem, the cerebellum and the cerebral hemispheres.
  • If the human brain is removed from the skull, it looks as if it has a handle or stem. The brain stem is one of the most primitive regions of the brain, and its functions are correspondingly basic – primarily control of physiological functions and automatic behaviours such as swallowing and breathing. The brains of some animals, such as amphibians, consist primarily of a brain stem and a simple cerebellum.
  • The two cerebral hemispheres constitute the largest, and most recently developed, part of the human brain.
  • The cerebellum, attached to the back of the brain stem, looks like a miniature version of the cerebral hemispheres. Its primary function is to control and coordinate movements, although recent research has highlighted its role in language and thinking, too (van Overwalle et al, 2020).
    Because the CNS is vital to an organism’s survival, it is exceptionally well protected. The brain is encased by the skull, and the spinal cord runs through the middle of a column of hollow bones known as vertebrae.

Question 22

CNS 2

Answer 22

• Both the brain and the spinal cord are enclosed by a three-layered set of membranes called the meninges (meninges is the plural of meninx, the Greek word for ‘membrane’; meningitis is an inflammation of the meninges). These are called, from the brain outward, the pia mater, arachnoid and dura mater.
  
  • A study published in 2023 suggested that there might even be a fourth layer, the subarachnoid lymphatic-like membrane (Mollgard et al, 2023). The brain and spinal cord do not come into direct contact with the bones of the skull and vertebrae. Instead, they float in a clear liquid called cerebrospinal fluid (CSF). This liquid fills the space between two of the meninges, thus providing a liquid cushion surrounding the brain and spinal cord and protecting them from being bruised by the bones that encase them.
  • The surface of the cerebral hemispheres is covered by the cerebral cortex (the word cortex means ‘bark’ or ‘rind’).
  • The cerebral cortex consists of a thin layer of tissue approximately 3 mm thick. It is often referred to as grey matter because of its appearance. It contains billions of nerve cells and is the structure where perceptions take place, memories are stored and plans are formulated and executed.
  • The nerve cells in the cerebral cortex are connected to other parts of the brain by a layer of nerve fibres called the white matter because of the shiny white appearance of the substance that coats and insulates them (myelin).
  • According to a recent study, the brain can be divided into at least 180 areas per hemisphere based on the architecture of these areas, connections between areas and function (Glasser et al, 2016). Of these, 87 are considered to be areas that had not previously been identified. White matter accounts for approximately 50 per cent of total brain volume (Bullock et al, 2022).
  • Tract or bundle is the name given to a collection of white matter nerves which share connectivity, volume, morphology, and trajectory and at least 20 different tracts have been identified (Bullock et al, 2022), including the corpus callosum, fornix, anterior commissure, internal capsule, superior and middle longitudinal fasciculus, and arcuate fasciculus.
  • The human cerebral cortex is wrinkled in appearance; it is full of bulges separated by grooves. The bulges are called gyri (singular ‘gyrus’), and the large grooves are called fissures. Fissures and gyri expand the amount of surface area of the cortex and greatly increase the number of nerve cells it can contain.
    Animals with the largest and most complex brains, including humans and the higher primates, have the most wrinkled brains and, thus, the largest cerebral cortices.

Question 23

Peripheral nervous system

Answer 23

• The peripheral nervous system consists of the nerves that connect the CNS with sense organs, muscles and glands. Nerves carry both incoming and outgoing information.
  
  • The sense organs detect changes in the environment and send signals through the nerves to the CNS.
  • The brain sends signals through the nerves to the muscles (causing behaviour) and the glands (producing adjustments in internal physiological processes).
  • Nerves are bundles of many thousands of individual fibres, all wrapped in a tough, protective membrane. Nerve fibres transmit messages through the nerve, from a sense organ to the brain or from the brain to a muscle or gland.
  • Some nerves are attached to the spinal cord and others are attached directly to the brain. The spinal nerves, attached to the spinal cord, serve all of the body below the neck, conveying sensory information from the body and carrying messages to muscles and glands.
  • The 12 pairs of cranial nerves, attached to the brain, serve primarily muscles and sense receptors in the neck and head. For example, when you taste food, the sensory information gets from your tongue to your brain through one set of cranial nerves.
    Other sets of cranial nerves bring sensory information to the brain from the eyes, ears and nose. When you chew food, the command to chew reaches your jaw muscles through another set of cranial nerves. Still other cranial nerves control the eye muscles, the tongue, the neck muscles and the muscles we use for speech

Question 24

Cells of the nervous system

Answer 24

• Neurons, or nerve cells, are the elements of the nervous system that bring sensory information to the brain, store memories, reach decisions and control the activity of the muscles.
  
  • Around 60 different types of neurons have been identified (Herculano-Houzel, 2009).
  • In 2018, a group of researchers discovered a new neuron that was found in the human brain but not in a rodent brain (Boldog et al, 2018). They called this the rosehip neuron and found that it was inhibitory (see later section on neurotransmission).
  • Neurons are assisted in their task by another kind of cell: the glia. Glia (or glial cells) get their name from the Greek word for glue and 90 per cent of cells in the brain are glial cells. They were first described in 1856 by the German anatomist, Rudolf Virchow.
  • At one time, scientists thought that glia simply held neurons – the important elements of the nervous system – in place. They do not, however, literally stick neurons together, but they do provide important physical support to neurons and provide other forms of mechanical support.
  • Some types of glial cells, such as astrocytes (the most common type) act on damage to neurons by helping repair them, regulate blood flow to cells and remove toxins (Opendak and Gould, 2015).
  • Other types are immune cells, which clear up debris in the brain (microglia) (Schafe et al, 2013).
  • Others (oligodendroglia) form protective insulating sheaths (myelin) around nerve fibres. The number of glial cells is higher in men than in women, around 28 per cent higher (Walloe et al, 2014). When brains are of equal size, however, this difference disappears. Like neurons, glial cells decline with age – there is an approximate 27 per cent loss
  • Research suggests that glial cells may play a more important part in brain development than was originally thought. For example, one study has shown that glial cells may determine the number of junctions between neurons – called synapses – generated in the brain (Ullian et al, 2001). This finding followed an experiment by researchers from the same laboratory which found that synapses of neurons grown with a certain type of glial cell were 10 times more active than those grown without.
    The mere proximity of glial cells to neurons made the neurons more responsive. In their most recent experiment, neurons that were exposed to glial cells formed seven times as many synapses as those that were not exposed. This is important because it indicates that glial cells have a much greater role to play in the formation of synapses in the CNS than had previously been thought. The next step is to identify how the glial cells produce this increase.

Question 25

The four principal parts of a neuron ;

Answer 25

1) The soma, or cell body, is the largest part of the neuron and contains the mechanisms that control the metabolism and maintenance of the cell. The soma also receives messages from other neurons.
2) The dendrites, the tree-like growths attached to the soma, function principally to receive messages from other neurons (dendron means ‘tree’). They transmit the information they receive down their ‘trunks’ to the soma.
3) The nerve fibre, or axon, carries messages away from the soma towards the cells with which the neuron communicates. These messages, called action potentials, consist of brief changes in the electrical charge of the axon. For convenience, an action potential is usually referred to as the firing of an axon. Many axons, especially long ones, are insulated with a substance called myelin which is white and gives some parts of the brain its whiteish appearance. The principal function of myelin is to insulate axons from each other and thus to prevent the scrambling of messages. It also increases the speed of the action potential. The immune systems of people who have multiple sclerosis attack a protein in the myelin sheath of axons, stripping it away. Although most of the axons survive this assault, they can no longer function normally, so, depending on where the damage occurs, people who have multiple sclerosis suffer from various sensory and motor impairments.
The terminal buttons are located at the ends of the ‘twigs’ that branch off the ends of axons. Terminal buttons secrete a chemical called a transmitter substance whenever an action potential travels down the axon, that is, whenever the axon fires. These chemicals are called neurotransmitters. The transmitter substance affects the activity of the other cells with which the neuron communicates. Thus, the message is conveyed chemically from one neuron to another. Most drugs that affect the nervous system and hence alter a person’s behaviour do so by affecting the chemical transmission of messages between cells

Question 26

Can the brain create new neurons? 1

Answer 26

• In the 1950s, Joseph Altman discovered that new neurons in some parts of the brain – specifically, the hippocampus and the olfactory bulb of rats – could be created.
  
  • The term for the creation of new neurons is neurogenesis. The type of neuron generated is a granule cell and these cells are found primarily in a specific part of the brain called the dendate gyrus of the hippocampus (Snyder and Cameron, 2012).
  • The first demonstration of neurogenesis in humans came in 2009 following the development of a new technique which used a chemical called BrdU, which made it easier to count cells in the brain (Eriksson et al, 1998).
  • The creation of these cells is seen in many mammals, including humans, and their production can be altered by environmental factors, such as stressors and even physical activity such as running or walking (Leuner and Gould, 2010; Schoenfeld and Gould, 2012; Spalding et al, 2013).
  • This idea that the creation of new cells can result from an environmental intervention is an example of neuroplasticity – the notion that the structure of the brain can be altered by behavioural and environmental factors (Opendak and Gould, 2015).
  • Experiments have shown that mild types of stressor can enhance neurogenesis but that unpredictable, chronic and intense periods of stress produced, for example, by sleep deprivation or electric shock, can inhibit it (Snyder et al, 2009; Lucassen et al, 2010).
    Some studies have found that parenting in non-human mammals can reduce neurogenesis (Leuner et al, 2010), probably because, despite being rewarding, looking after offspring is very stressful.

Question 27

Can the brain create new neurons? 2

Answer 27

• One mechanism which may underpin this reduction is the inhibition of progenitor cells. That is, the cells that lead to the creation of new neurons are impaired by the experience of stress (Schoenfeld and Gould, 2012). The ultimate cause of this inhibition is likely to be the production of glucocorticoids, stress-chemicals which are released when an organism experiences stress
  
  • Glucocorticoids exert a number of negative effects on behaviour if their release is prolonged; people’s immune system works ineffectively, for example, or their memory and ability to navigate their way around an environment becomes impaired (Conrad, 2008).
  • Stress also exerts effects on the shape and size of some elements of existing neurons; the complexity of dendrites is reduced, for example, as is the number of spines on dendrites and the number of synapses in the hippocampus (McEwen, 2012).
  • The opposite response – a behaviour leading to neurogenesis – has been found in animals when they engage in physical activity such as exercise or sex and even when they live in an enriched environment or are administered cocaine (Opendak and Gould, 2015). For example, in non-humans such as rodents, running on a treadmill or a wheel has been associated with increased numbers of neurons in the hippocampus (Vivar and Van Praag, 2013) although there is evidence that if the running is done alone or the physical exercise is very intense then neurogenesis does not happen (Opendak and Gould, 2015). Whether such effects can be produced in humans – where the rewarding nature of the running depends on individual differences and our motivation – is not known.
  • Whether new cells are function-specific or just add to the pool of neurons that can be recruited to perform a range of behaviours is also unknown.
  • In their review, Opendak and Gould (2015) noted that when new cells are created as a result of spatial navigation learning, these cells are more responsive when they are exposed to spatial cues than other types of cue, suggesting that they may have a degree of specificity. The type of function that cells have also seems to be determined by where the cells are created.
  • The other important question is: why are these new cells produced in the first place? According to Opendak and Gould (2015), the hippocampus’s ability to generate new cells which can be altered by environmental factors ‘strongly suggests that new neurons are a substrate for sculpting the brain to produce behaviours that are adaptive for the organism’ (p. 6).
  • They go on to argue that the reduction of neurogenesis can also be an advantage because the stress which creates this leads to increased anxiety and reduced exploration, which might help survival. It is an intellectual leap, but it is one explanation.
    There is also some evidence to suggest that once the cells are created they do not simply survive; they have to be used. For example, it is not enough for an animal to be trained for the cells to continue; the animal has to learn. If it learns, the new cells are more likely to survive (Shors, 2014)

Question 28

Neurotransmitters

Answer 28

There are currently around 50, or so, identifiable neurotransmitters and all are important to behaviour in some way. Some, however, play a greater role than others. The amine group of neurotransmitters, which includes dopamine, noradrenaline and serotonin (5-hydroxytryptamine), appears especially important to psychologists because they are involved in a range of behaviours – emotional expression, decision-making, response to reward, inhibiting inappropriate actions, drug-taking and many others (Azizi, 2020). Their effect on nerve cells is binary: they can inhibit, or they can excite.

neurotransmitter table in notes

* A part of the brain called the nucleus accumbens appears to be important in this respect and seems to be part of a reward system located in the front and midpart of the brain. It evaluates how salient or important events in the outside world are. It and the system it belongs to are also implicated in impulsive behaviour – the inability to delay reward and be aware of the consequences of actions, and so on (Pothuizen et al, 2005) – and drug addiction (Russo et al, 2010; Everitt and Robbins, 2013). 
* Norepinephrine and dopamine are thought to increase attention; drugs acting on these are used to manage attention disorders (Cortese, 2020). Drugs which act on serotonin receptors increase impulsivity (Pattij and Vanderschuren, 2008) and this impulsivity, according to some scientists, is linked to the initiation and maintenance of drug-seeking (Krishnan-Sarin et al, 2007). There is also evidence that there is an increase in the density of the spines of dendrites in the nucleus accumbens when cocaine or heroin is administered (Shen et al, 2009; Maze et al, 2010).
* The events to which the nucleus accumbens responds include rewarding stimuli (food, water, sex), aversive stimuli (ice, shock) and novel stimuli. Dopamine release increases here, as does the firing of dopamine receptors when an organism is rewarded with food or water (Iversen and Iversen, 2007; Schultz, 2007).Dopamine can increase by as much as 20–100 per cent and last for up to 100 minutes (Schultz, 2007). 
* If an organism expects a reward, then there is a release of dopamine in these regions, but if an organism is completely rewarded there seems to be little dopamine activation. Dopamine is also released in freely moving organisms, which suggests that it is important for motor movement and the motivation to move. 
* Of course, the movement disorder Parkinson’s disease, discussed a little later, is treated by a dopamine precursor (called Levodopa), and excessive dopamine is thought to be implicated in some of the symptoms of schizophrenia 
* Like all the amines, dopamine receptors begin projecting from the brain stem and certain dopamine receptors terminate (end their projections) in the front part of the brain, called the prefrontal cortex (PFC), described below. These receptors, called D1 receptors, appear to be very important to cognitive performance and influence tasks such as our ability to store and manipulate non-verbal information over very short periods of time – a type of memory called working memory  Some people have a mutation of an allele which directly affects dopamine (by deactivating it) with the consequence that their cognitive function is impaired (Tunbridge et al, 2006). Another type of dopamine receptor, D2, seems to be reduced in the striatum of drug addicts (Kalivas and Volkow, 2005).

Question 29

Action potential

Answer 29

• The message carried by the axon – the action potential – involves an electrical current, but it does not travel down the axon the way electricity travels through a wire. Electricity travels through a wire at hundreds of millions of metres per second. The axon transmits information at a much slower rate – less than 100 metres per second.
  
  • The membrane of an axon is electrically charged. When the axon is resting (i.e. when no action potential is occurring), the outside is charged at +70 millivolts (mV, thousandths of a volt) with respect to the inside.
  • An action potential is an abrupt, short-lived reversal in the electrical charge of an axon. This temporary reversal begins at the end of the axon that attaches to the soma and is transmitted to the end that divides into small branches capped with terminal buttons.
  • The electrical charge of the axon occurs because of an unequal distribution of positively and negatively charged particles inside the axon and in the fluid that surrounds it. These particles, called ions, are produced when various substances – including ordinary table salt – are dissolved in water.
  • Normally, ions cannot penetrate the membrane that surrounds axons. However, the axonal membrane contains special submicroscopic proteins that serve as ion channels or ion transporters. Ion channels can open or close; when they are open, a particular ion can enter or leave the axon. Ion transporters work like pumps. They use the energy resources of the cell to transport particular ions into or out of the axon.
  • The outside of the membrane is positively charged (and the inside is negatively charged) because the axon contains more negatively charged ions and fewer positively charged ions. When an axon is resting, its ion channels are closed, so ions cannot move into or out of the axon.
  • An action potential is caused by the opening of some ion channels in the membrane at the end of the axon nearest to the soma. The opening of these ion channels permits positively charged sodium ions to enter, which reverses the membrane potential at that location. This reversal causes nearby ion channels to open, which produces another reversal at that point. The process continues all the way to the terminal buttons located at the other end of the axon.
    Note that an action potential is a brief reversal of the membrane’s electrical charge. As soon as the charge reverses, the ion channels close and another set of ion channels opens for a short time, letting positively charged potassium ions out of the axon. This outflow of positive ions restores the normal electrical charge. Thus, an action potential resembles the ‘Mexican wave’ that football fans often make in a stadium. People in one part of the stadium stand up, raise their arms over their heads, and sit down again. People seated next to them see that a wave is starting, so they do the same – and the wave travels around the stadium. Everyone remains at the same place, but the effect is that of something circling in the stands around the playing field. Similarly, electricity does not really travel down the length of an axon. Instead, the entry of positive ions in one location reverses the charge at that point and causes ion channels in the adjacent region to open, and so on. The ion transporters pump sodium ions out of the axon and pump potassium ions back in, restoring the normal balance

Question 30

Synapses

Answer 30

• Neurons communicate with other cells by means of synapses. A synapse is the conjunction of a terminal button of one neuron and the membrane of another cell – neuron, muscle cell or gland cell.
  
  • The terminal button belongs to the presynaptic neuron – the neuron that sends the message. When terminal buttons become active, they release a chemical called a transmitter substance. The neuron that receives the message (detects the transmitter substance) is called the postsynaptic neuron.
  • A neuron receives messages from many terminal buttons, and in turn its terminal buttons form synapses with many other neurons.
  • thousands of terminal buttons can form synapses with a single neuron
  • A motor neuron is one that forms synapses with a muscle and controls its contractions. When the axon of a motor neuron fires, all the muscle fibres with which it forms synapses will contract with a brief twitch.
  • A muscle consists of thousands of individual muscle fibres. It is controlled by many motor neurons, each of which forms synapses with different groups of muscle fibres.
    The strength of a muscular contraction, then, depends on the rate of firing of the axons that control it. If they fire at a high rate, the muscle contracts forcefully; if they fire at a low rate, the muscle contracts weakly.

Question 31

Excitation and inhibition

Answer 31

• There are broadly two types of synapse: excitatory synapses and inhibitory synapses. Excitatory synapses do just what their name implies. When the axon fires, the terminal buttons release a transmitter substance that excites the postsynaptic neurons with which they form synapses. The effect of this excitation is to make it more likely that the axons of the postsynaptic neurons will fire. Inhibitory synapses do just the opposite. When they are activated, they lower the likelihood that the axons of the postsynaptic neurons will fire.
  
  • The activity of the synapses on the dendrites and soma of the cell determines the rate at which a particular axon fires. If the excitatory synapses are the more active, then the axon will fire at a high rate. If the inhibitory synapses are the more active, then the axon will fire at a low rate or perhaps not at all.
  • How do molecules of transmitter substance exert their excitatory or inhibitory effect on the postsynaptic neuron? When an action potential reaches a terminal button, it causes the terminal button to release a small amount of transmitter substance into the synaptic cleft, a fluid-filled space between the terminal button and the membrane of the postsynaptic neuron.
  • The transmitter substance causes reactions in the postsynaptic neuron that either excite or inhibit it. These reactions are triggered by special submicroscopic protein molecules embedded in the postsynaptic membrane called receptor molecules.
  • A molecule of a transmitter substance attaches to a receptor molecule in the way that a key fits in a lock. After their release from a terminal button, molecules of transmitter substance find their way to the receptor molecules, attach to them and activate them.
  • Once they are activated, the receptor molecules produce excitatory or inhibitory effects on the postsynaptic neuron. They do so by opening ion channels. The ion channels found at excitatory synapses permit sodium ions to enter the neuron; those found at inhibitory synapses permit potassium ions to leave it
  • The excitation or inhibition produced by a synapse is short-lived; the effects soon pass away, usually in a fraction of a second. At most synapses, the effects are terminated by a process called reuptake. The transmitter substance is released by the terminal button and is quickly taken up again. It has, therefore, only a short time to stimulate the postsynaptic receptor molecules.
  • The rate at which the terminal button takes back the transmitter substance determines how prolonged the effects of the chemical on the postsynaptic neuron will be.
    The faster the transmitter substance is taken back, the shorter its effects will be on the postsynaptic neuron. As we will see, some drugs affect the nervous system by slowing down the rate of reuptake, thus prolonging the effects of the transmitter substance

Question 32

Neuromodulators - action at a distance

Answer 32

• Terminal buttons excite or inhibit postsynaptic neurons by releasing transmitter substances. These chemicals travel a very short distance and affect receptor molecules located on a small patch of the postsynaptic membrane. But some neurons release chemicals that get into the general circulation of the brain and stimulate receptor molecules on many thousands of neurons, some located at a considerable distance away.
  
  • The chemicals these neurons release are called neuromodulators, because they modulate the activity of the neurons they affect.
  • We can think of neuromodulators as the brain’s own ‘drugs’. Because these chemicals diffuse widely in the brain, they can activate or inhibit many different circuits of neurons, thus exerting several behavioural and physiological effects. These effects act together to help achieve a particular goal.
  • The best-known neuromodulator is a category of chemicals called endorphins, or opioids (‘opium-like substances’).
  • Opioids are neuromodulators that stimulate special receptor molecules (opioid receptors) located on neurons in several parts of the brain. Their behavioural effects include decreased sensitivity to pain and a tendency to persist in ongoing behaviour. Opioids are released while an animal is engaging in important species-typical behaviours, such as mating or fighting. The behavioural effects of opioids ensure that a mating animal or an animal fighting to defend itself is less likely to be deterred by pain; thus, conception is more likely to occur, and a defence is more likely to be successful.
  • Many years ago, people discovered that eating or smoking the sap of the opium poppy decreased their sensitivity to pain, so they began using it for this purpose.
  • They also discovered that the sap produced pleasurable effects: people who took it enjoyed the experience and wanted to take more.
  • In recent times, chemists have discovered that the sap of the opium poppy contains a class of chemicals called opiates. They also learned how to extract and concentrate them and to produce synthetic versions with even greater potency.
  • In the mid-1970s, neurobiologists learned that opiates produce their effect by stimulating special opioid receptor molecules located on neurons in the brain (Pert et al, 1974). Soon after that, they discovered the brain’s opioids (Terenius and Wahlström, 1975). Thus, opiates mimic the effects of a special category of neuromodulators that the brain uses to regulate some types of species-typical behaviours.
    The brain produces other neuromodulators. Some help organise the body’s response to stress, while others reduce anxiety and promote sleep. Some promote eating, while others help end a meal.