Introduction to Biological Psychology Part III Chapter 5 Neuronal Transmission

202 NEURONAL . NEURONAL TRANSMISSION Catherine Hall Learning Objectives By the end of this chapter , you will understand that neurons signal electrically within each cell and chemically between cells the ionic basis of the action potential and how it is conducted the processes involved in synaptic transmission how neurons integrate information at .

NEURONAL 203 In the last chapter , we learnt about electrical signalling in the brain and how electrochemical gradients and ion channels allow neurons to set their membrane potential . In this chapter we will learn how these processes generate the signals within and between neurons that form the basis for the information processing in the brain . Signals are transmitted electrically within neurons and chemically between neurons , at synapses . Electrical signals within neurons take the form of action potentials and synaptic potentials . We can talk of electrical signals in cells as producing a positive change in the membrane potential termed , or a negative change in the membrane potential , termed .

204 Action potentials MEMBRANE non ) mum Fig . An action potential is a transient voltage change that spreads from the axon hillock to the axon terminals . An action potential is a brief electrical signal that is conducted from the axon hillock where the neuron soma joins the axon , along the axon to the axon terminals . It can be measured from electrodes placed in or near a neuron connected to a voltmeter ( Figure ) This electrical signal is a rapid , localised change in the membrane voltage which transiently changes from the negative resting membrane potential to a positive membrane potential . A positive shift in the membrane potential like this is termed . The membrane then rapidly ( within ) becomes negative again it and then shifts even more negative , becoming before returning to the resting membrane potential less than after it first ( Figure ) This transient voltage

NEURONAL TRANSMiSSiON i 205 change then spreads like a wave down the axon with a conduction velocity of between and 100 7715 At PO TEN ow ( amine em a aromas ) Fig . Membrane potential changes during an action potential . The action potential is caused by opening and closing of ion channels What is happening within the axon to cause these changes in membrane voltage ?

As discussed above , the way in which neurons generally alter 206 I their membrane potentials is by changing their membrane permeability to different ions by opening and closing ion channels , and that is exactly what is happening during the action potential . The ion channels that open and close to form the action potential are ion channels . As their name suggests , these channels open or close depending on the voltage across the membrane . There are many types of ion channels , which differ in their thresholds for activation the voltages at which they open and close as well as their selectivity for ions . When they open , ions down their electrochemical gradients towards their equilibrium potentials . sodium and potassium channels open to then the membrane

I 207 , er , miss . Pai ops ion Aw ( name no MEMBRANE Alf , i vi , i a ' Fig The action potential is caused by the opening and closing of voltage gated ion channels . The upstroke ( when the voltage rapidly ) of the action potential ( Figure ) is caused by the opening of sodium channels that have a threshold for opening of . When the membrane of the neuron to , these sodium channels start to open . Sodium ions into the cell , the membrane and opening even more sodium channels , causing a very rapid of the membrane . This activation of sodium channels makes the action potential an all or nothing event ( it either happens , or it does not ) If the threshold is reached , sodium channels open , accelerating

208 NEURONAL happens and an action potential occurs ( or ) If the threshold is not reached , sodium channels do not open and no action potential will . Furthermore , the action potential is always the same size and is not graded by the size of the incoming . If the sodium channels stayed open , then the membrane potential would stabilise at the equilibrium potential for sodium ( at , but instead the voltage reaches only around before again , so the membrane is for less than . The is so brief for two reasons firstly , the sodium channels rapidly inactivate , closing the channel and preventing further to the cell . Secondly , a second type of channel activates the potassium channel . Some of these potassium channels activate at the same threshold as the sodium channels but more slowly , and others activate at a more positive voltage ( around ) Both these factors mean that opening of gated potassium channels is delayed relative to the . When channels open , however , leaves the cell , causing the membrane to become more negative , or , producing the falling phase or downward stroke of the action potential ( Fig .

NEURONAL 209 Increased permeability causes an Many potassium channels switch off quite slowly after the membrane potential Falls below their threshold voltage . This means that after the membrane potential has , reaching the resting membrane potential , there are still some potassium channels open , in addition to the potassium leak channels that are always open . Because the membrane is now more permeable to than at rest , the membrane potential below the resting membrane potential , getting even nearer to the equilibrium potential for , EK . This phase is termed the . Then as the potassium channels close , the permeability of the membrane for potassium returns to normal and the membrane potential slightly back to the resting membrane potential .

210 i vo ro warmly MEMBRANE ( Fig . Permeability ot the membrane to sodium and potassium during the action potential Sodium channel inactivation causes the refractory period for action potential The opening and closing of sodium and potassium channels at different threshold voltages and inactivation of sodium channels occur because gates in the proteins move to open and close the pore region in the centre of the channel that allows ions to flow across the membrane ( Figure ) At the resting membrane potential , gated sodium and potassium channels both have a

211 conformation or shape that means part of the protein blocks the ion channel pore ( it is like there is a closed gate blocking the pore ) When the threshold voltage is reached , the shape of the ion channel proteins change slightly so that this gate opens to let ions through . This gate opens quickly in sodium channels but more slowly , or at more potentials in potassium channels , so during the rising phase of the action potential only the sodium channel gates are open . After a very short time , however , an inactivation gate on the intracellular side of the sodium channel swings shut , blocking the pore from the inside and stopping any more . As the potassium channels open , during the falling phase of the action potential , voltage gated sodium channels are . Even when the membrane falls below the threshold voltage , closing the gate , the sodium channels inactivation gates are still closed . This means that the sodium channels can not , and the neuron can not another action potential until the inactivation gates reopen . This period of time when of another action potential is impossible is called the absolute refractory period ( Figure ) Sodium channels inactivation gates start to reopen during the falling phase of the action potential , when gated potassium channels are still open . At this stage , it becomes possible to another action potential , but a stronger stimulus is needed to activate the sodium channels .

212 i NEURONAL This period is the relative refractory period ( Figure ) Stronger stimuli ( that a neuron more ) can therefore produce a faster rate in a target neuron than weaker stimuli by intruding into the relative refractory period . REM ! ea mAL Ea ro was 70 MEMBRANE POTENTIAL ( AV ) mov Fig . Absolute and relative refractory periods Action potential propagation Action potentials are initiated in the axon initial segment near the soma , right next to the axon hillock . If the membrane potential there sufficiently to trigger sodium channels to open , then an action potential will in

NEURONAL 213 that section of membrane . In an unmyelinated axon ( Figure ) some of the positive charge ( ions ) that enters the cell during the rising phase of the action potential spreads to the adjacent bit of membrane , that membrane and opening sodium channels there , producing an action potential , which spreads onwards to the next bit of membrane , such that a wave of and spreads down the axon all the way to the axon terminals . Sodium channel inactivation prevents upstream spread of the action potential back towards the soma because the upstream membrane is in the absolute refractory period , the action potential can only spread downstream to membrane in which sodium channels are not .

214 i TRANSMISSION , moan TED AXON . co a a men Move or Fig 326 . Action potential propagation in myelinated and unmyelinated axons Increasing the axon diameter and the axon increases conduction speed Action potentials spread quite slowly along small unmyelinated axons around because each bit of membrane has to fire an action potential and propagate it to the next bit of membrane . This speed of conduction would be too slow to get information about what is going on

NEURONAL 215 at the far end of our bodies imagine wiggling your toe and only knowing seconds later that you actually had wiggled it ! Luckily , action potential conduction can be increased in two major ways . Firstly , conduction speed is increased by increasing the diameter of the axon , which reduces the resistance to current within the axon , allowing to passively spread further down the axon and therefore more rapidly activate action potential in downstream membrane . Secondly , myelination of axons increases conduction speed . The layers of myelin that are tightly wrapped around axons by ( in the ) or cells ( in the ) insulate the axon membrane from current loss across the membrane . Axon membrane in myelin layers does not contain ion channels it has low permeability and high resistance to current flow . This allows current to spread further inside the axon without leaking out of the cell , allowing current to spread Further down the axon without being dissipated . The myelin sheath also decreases the membrane capacitance the amount of charge stored at the membrane . Charge gets stored at the membrane when positive and negative charges are attracted to each other across the thin plasma membrane , holding them near each other at opposite sides of the membrane . By wrapping tightly around the membrane , myelin increases the distance between the intracellular and extracellular containing charged particles so they are less attracted to each other across the

216 NEURONAL membrane . The lowered capacitance allows current to spread further ( and faster ) inside the axon as ions do not get stuck at the membrane . The result of myelination is that can rapidly spread passively along relatively long distances of axon , but it can not spread down the whole length of the axon . The signal still needs to be boosted periodically by generating a new action potential . This happens at nodes of , which are gaps in the myelin sheath that are packed with ion channels . When the nodes of , their sodium channels open , triggering a new action potential which can then passively spread across the internode region of the axon to the next node of ( Figure ) Because the action potential rapidly jumps between nodes , this form of conduction is called saltatory conduction ( from Latin to jump ) Large diameter , myelinated axons can conduct action potentials at speeds up to 100 , meaning information about can reach your brain in a respectable Indeed , sensory neurons carrying information about where our bodies are in space have some of the fastest propagating axons of any cell . conditions , such as multiple sclerosis and Syndrome , cause a multitude of symptoms , including altered sensation , muscle weakness and cognitive , due to loss of myelin sheaths , disrupted neuronal communication and eventual axonal degeneration .

I 217 Energy use by action potentials The How of ions through ion channels during the action potential occurs down their electrochemical gradients so it does not itself use energy . During an action potential very few ions actually How so the concentration gradients do not change over the short term . Over the longer term , however these ions need to be pumped back to maintain concentration gradients and the resting membrane potential so that further action potentials can . This is achieved by the , using , Myelination of axons helps speed action potential conduction , but also makes action potential more energy efficient , because fewer ions need to How to the myelinated membrane . Fewer ions therefore need to be pumped back across the membrane , so less is needed by the . Action potential Key takeaways When the membrane reaches a threshold voltage , sodium channels briefly open , the cell

218 NEURONAL potassium channels open and the cell spreads along the membrane activating nearby sodium channels Inactivation of sodium channels means action potential propagates in one direction and sets a limit on frequency Action potentials are , and only occur once the threshold for sodium channel activation is met Myelination speeds action potentials and makes them more . Communication between neurons Neurons signal electrically , using action potentials to communicate between the soma and the axon terminals . The action potential signals that the soma and axon initial segment to the threshold voltage . But what generates that in the first place ?

What is the signal that a neuron to make it an action NEURONAL 219 potential ?

We saw in chapter that neurons integrate lots of inputs and compute whether or not to an action potential . In sensory neurons , these inputs to a neuron might be information from the outside ( or internal ) world , for example stretch of the skin , a painful heat , or a delicious smell . You will learn more about how these types of stimuli generate inputs in neurons in later chapters . But For most neurons , the inputs come from other neurons , via connections , or synapses . While neurons communicate electrically within a cell , communication between neurons is usually chemical a chemical or neurotransmitter is released from one neuron and acts to generate a signal on the next neuron . Synaptic transmission During synaptic transmission , an action potential in a neuron the presynaptic neuron causes a neurotransmitter to be released into a tiny gap called the synaptic cleft between two neurons . The neurotransmitter diffuses across the synaptic cleft and binds to receptors on the neuron receiving the signal the postsynaptic neuron , which produces a change in the postsynaptic cell . Looking into this process in more detail , we can split the processes of synaptic transmission into a number of separate steps ( Figure )

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NE ! anew I my mace ever AV mac ro ) Fig . Synaptic transmission ' An action potential arrives at the axon terminal ( or presynaptic terminal ) of the presynaptic terminal opens a new type ion channel the calcium channel , which has a threshold for activation of around . When these channels open , calcium ( enters the cell down its electrochemical gradient , as there is a higher concentration in the extracellular compared to the intracellular ( outside the cell , inside the cell ) and its positive charge attracts it into the negatively charged cell . Unlike and , is not present at

I 221 high enough concentrations to affect the membrane potential of the cell . Instead , an increase in intracellular concentration can trigger different signalling cascades in the cell , by binding to different proteins . entering through calcium channels binds to a protein called . The presynaptic terminal contains lots of little membrane bags called synaptic , which are packed with neurotransmitter . Some of these are close to an area on the plasma membrane of the cell called the active zone , whereas the that are still being packed with neurotransmitter are further away from the membrane and nearer the centre of the presynaptic terminal . The at the active zone are docked , being held close to the plasma membrane by a complex of proteins called SNARE proteins . When calcium binds to , the membranes of the vesicle and the plasma membrane of the cell are brought even closer together and fuse , releasing the contents of the vesicle ( neurotransmitter molecules ) into the extracellular space of the synaptic cleft . The that are already clocked at the active zone are more readily released so are the first to fuse with the membrane and release their neurotransmitter . The synaptic cleft is very narrow , so neurotransmitter molecules can quickly diffuse across from the presynaptic terminal to the cell .

222 I ' The postsynaptic cell membrane ( usually part of a dendrite ) contains receptors for the neurotransmitter molecules that are released from the presynaptic cell . A receptor is a protein that can bind a molecule termed a . Many of these receptors are part of ion channels . These are ion channels that open when a molecule binds to them . Ions through the open ion channels , down their electrochemical gradients , producing a change in the membrane voltage in the ' To terminate synaptic signalling , neurotransmitter must be removed from the synaptic cleft . This is achieved by transporters on neurons or , proteins which take up neurotransmitter into the cell where it can be broken down , recycled or repackaged . Some neurotransmitters may also be broken down by proteins that are present in the synaptic cleft . Excitatory synapses Excitatory synapses make the neuron more likely to an action potential by producing a in the cell , moving it towards the threshold potential for opening sodium channels . This happens when ions are allowed to How into the cell . The main excitatory neurotransmitter in the brain is glutamate ( acetylcholine is an important excitatory

I 223 neurotransmitter in the peripheral nervous system ) Glutamate main receptors are and receptors . receptors are ion channels that let both and pass through them . Though ions leave the cell when receptors open , the main effect is an of , so when glutamate binds receptors , the membrane towards the threshold for an action potential . This change in membrane potential is termed an excitatory potential ( Figure ) and lasts several ( 10 ) milliseconds , VON mux Runs lass amps cu . Ex , I ( 50 Fig . Glutamate binding to receptors causes

224 NEURONAL receptors are also ion channels and are permeable to as well as and . However they are also , as they are blocked by ions unless the membrane potential is . They are also slower than receptors to open and close . Because of this they do not contribute much to the . However they play a really important role in altering synaptic strength or how much of an effect a presynaptic action potential can have on the postsynaptic cell . glutamate receptors are often also present . receptors are also known as coupled receptors . These proteins bind glutamate but do not directly open an ion channel . Instead they trigger other intracellular signalling pathways that can make other changes to the cell , for example altering the properties of other ion channels . Because their action is via intracellular signalling pathways , they have slower effects than receptors ( receptors such as and receptors that are part of , and directly activate , ion channels )

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low Liam new am mus I mam ma WOW Acre ' re mam VON ME ) RECEPTOR , or tum loll st was scam Fig . and glutamate receptors Usually an from a single synapse won the neuron enough to reach the threshold for an action potential . Instead multiple synaptic inputs need to be summed together to get a big enough ( Figure ) If the presynaptic neuron lots of action potentials in a short space of time , then the inputs into a single synapse can add together to form a larger , This is temporal summation . Additionally , if different excitatory synapses are active at the same time , then these can spatially summate to generate a larger . Both temporal and spatial summation happen to integrate the inputs onto a postsynaptic cell , to determine whether it an action potential .

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ADD am my to AP ! to re ! OF OF Fig . Summation of Inhibitory synapses Inhibitory synapses make the neuron less likely to an action potential , by the membrane , or by preventing it from by holding the membrane below that needed to activate sodium channels . The main inhibitory neurotransmitter in the brain is ( gamma acid ) whose main receptors are and receptors . receptors are ion channels that are permeable to ions when

I 227 is bound . Because ions enter the cell on activation and the equilibrium potential for ( is , opening channels will tend to keep the membrane potential near . As this is below the threshold For activation of sodium channels , this will inhibit the neuron from an action potential . Depending on the membrane voltage of the cell when these channels open , the membrane potential might slightly or the cell . In each case , however , this membrane potential change is inhibitory ( an inhibitory potential or ) because it is holding the membrane potential away from that needed to an action potential . For example , if the neuron membrane potential is when receptors open , the membrane potential will move towards so will slightly to . However the open receptors prevent the membrane from beyond to the threshold for an action potential . If the membrane potential is more positive than EC , then opening channels will make the membrane potential more negative or , until it reaches . In both cases , opening the channels has made the neuron less likely to reach threshold for action potential . receptors are receptors that are linked to activation of potassium channels , increasing permeability . Their activation therefore shifts the membrane potential towards EK , or , the cell .

228 I membrane potential changes are therefore also as they the membrane away from the threshold for action potential , but because they require intracellular signalling these are slower than membrane potential changes . mam An rams , INHIBITOR ) loll . A ' raw aim UN wrath MEMBRANE Fig . Inhibitory synapse Synaptic integration Postsynaptic cells use temporal and spatial summation to integrate all the different synaptic inputs to the cell . If the net effect of all the inputs is to the axon initial segment above the threshold for activating sodium channels , the cell

229 will an action potential . The way in which all these inputs are integrated to generate an output ( action potential ) is therefore the basis of how neurons perform the computations on which our thoughts and feelings depend . Neurons can perform different computations based on their morphology and the spatial organisation of their excitatory and inhibitory inputs , as this alters how they are ( Fig . Most synaptic inputs are onto the dendrites of a neuron , but some may be onto the soma or even the axon . Synaptic inputs to the distal end of dendrites ( far from the soma ) will potentially have a smaller effect on the membrane potential at the axon initial segment than an input onto the soma , because the signal degrades over the distance they need to travel , while inputs onto the axon initial segment itself can have an even stronger effect than those onto the soma . Excitatory inputs onto distal dendrites can also be gated by inhibitory synapses that are more proximal to the soma on the same dendrite , so the can not reach the soma . The ability of and to spread along dendrites is also determined by factors such as the number and type of ion channels in the dendritic membranes , as well as the size of the cell . If there are few ion channels , then charge can not as easily leak out across the membrane and dissipate the potential chance . Similarly , a given input will spread further in a small cell than a larger , highly branched cell , as less charge gets lost at the membrane ( the smaller cell has a lower capacitance )

230 However , dendrites also express ion channels that can boost signals from distal dendrites . AT AXON HEW OF OF ! EFFECTIVE OF FROM ! FROM 31 i I , am Mom me man can sow size an aim we were THAN THAN , Ex aw BE BY 50057217 ) EXPRESSION OF ' MORE VOLTAGE snip A Fig Synaptic integration Neurons computation can therefore be affected by many factors , from the location and strength of individual synapses , to the shape of the cell and the number and location of ion channels expressed . Many of these properties can be based on the cell activity , allowing alterations to the

231 contribution that different synaptic connections play on the decision to an action potential . This plasticity in synaptic connectivity is critical for allowing associations to be formed and broken between neurons , forming the basis of learning and memory as well as shaping how we perceive the world . Gap Junctions While most connections between neurons are via chemical synapses , direct electrical connections also occur . These are called gap junctions and are formed by pairs of , one on each cell , made up of a complex of proteins called . Compared to other ion channels , gap junctions are relatively , allowing ( ions ) and ( ions ) through as well as small molecules such as . Though regulation of their opening is

232 NEURONAL possibly , they are usually open , meaning that electrical signals can spread through connected cells . Gap junctions are more common during development and are rare between excitatory cells in mature nervous systems . They are most common between certain inhibitory in the brain and the retina , as well as between glia , such as . Closed Open monomer Plasma spun space Fig . Gap junction coupling between cells

NEURONAL 233 Other neurotransmitters While glutamate is the main excitatory neurotransmitter in the brain , and is the main inhibitory neurotransmitter in the brain , there are many other neurotransmitters that can also be released at synapses . These can be broadly divided in to different categories , based on the chemical structure of the neurotransmitter molecules . All activate their own receptors . Amino acid neurotransmitters include glutamate , and also glycine , which is the major inhibitory neurotransmitter in the brainstem and spinal cord . Monoamine neurotransmitters include , dopamine and serotonin . There are populations of neurons in the brain that originate in midbrain and brainstem nuclei and send projections to widespread brain regions , modulating processes such as reward , attention and alertness . is also an excitatory transmitter in the peripheral nervous system . Peptide neurotransmitters include naturally occurring opioid peptides endorphins , and that activate the same receptors as opiate drugs such as morphine and heroin . There are numerous other peptide neurotransmitters , including oxytocin and .

234 NEURONAL TRANSMISSION Peptide neurotransmitters are often at synapses with or serotonin . Purine neurotransmitters include , the cell main energy currency , and its breakdown product adenosine . Acetylcholine is unlike other neurotransmitters structurally . It is a common excitatory neurotransmitter in the peripheral nervous system , including at the neuromuscular junction , and is also released by many neurons in the brain , where it is involved in regulating alertness , memory and attention , Synaptic transmission Key takeaways When an action potential arrives at an axon terminal , calcium channels open , allowing influx into the terminal binds , pulling synaptic very close to the plasma membrane . This triggers fusion of synaptic with the plasma membrane , releasing

NEURONAL 235 neurotransmitter into the synaptic cleft . Neurotransmitter diffuses across the synaptic cleft and binds to or receptors on the postsynaptic cell . Receptors for excitatory neurotransmitters such as glutamate trigger entry into the postsynaptic cell , the membrane ( producing an ) making it more likely the postsynaptic cell will to the threshold for an action potential . Inhibitory neurotransmitters such as activate receptors that keep the membrane potential negative with respect to the threshold for an action potential ( generating an ) Postsynaptic neurons integrate different excitatory and inhibitory inputs to decide an action potential . The location and strength of different synapses , as well as the shape of the synaptic cell and expression of different ion channels modify the integration of different inputs changing these can alter the computation done by the cell .

236 I About the Author Catherine Hall UNIVERSITY OF Catherine Hall is a member of the Neuroscience Steering Committee , the University Senate , convenes the core first year module , and lectures on topics relating to basic neuroscience , neurovascular function and dementia .