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Communication between Neurons Properties of Synaptic Conduction Temporal Summation: Spatial Summation Inhibitory Synapses The Structures of the Synapse: Vessicles Pre-synaptic membrane Post synaptic membrane Sequence of chemical events at the synapse Synthesis of neurotransmitters Release of neurotransmitters Action of neurotransmitters on Post Synaptic membrane Reuptake or break down of neurotransmitters Reading Pinel, Biopsychology, Section 4.5-4.8 Or Carlson Physiology of Behavior, Pages 42-52 Aims To provide you with a list of the basic structures and chemicals involved with information passing between neurones and to describe the various steps involved. To point out how this process differs from how the message travels along the neurone. Objectives By the end of this lecture you should be able to list the important structures at the terminal button. You should also be able to describe the stages of the process and how it differs from an action potential. How do we know this is different from communication within a nurone? Initially we thought it was one long bit of neurone with all communication via electrical action potentials and saltatory conduction, branching into spinal cord (Whytte 1730) Santiago Ramon y Cajal late 1800 studied slides of infant brains under the microscope. He wanted to be an artist so he illustrated nerve cells and demonstrated that neurones did not merge they were separated by a gap. Charles Sherrington in 1906 called this gap a synapse and from his largely behavioural studies was able to deduce most of the major properties of the synapse. What Sherrington did was to very lightly pinch the paw of a dog and to time how long before the dog would pull back his foot. He was basically looking at the same type of reflex we’ve looked at before where you burn your finger and withdraw your hand. He found this reflex withdrawal was happening too slowly if this was all happening via action potentials. Eg speed of action potential 40 m/s conduction through a reflex arc is 15m/s. delay must be happening at synapse. Properties of Synaptic Conduction Sherington discovered 3 important properties of the synapse i) Temporal Summation: He discovered if you pinched the dogs foot very very lightly there was no response, if you did this 3 times in rapid succession the dog would withdraw the foot. The more rapid each pinch followed on from the other the more strong the response. Sherington surmised a single light pinch was too light to set off an action potential in the next cell along but another pinch just after the first would combine in some way with the first to set off the next cell. John Eccles (1964) recorded activity in single neurones to show temporal summation. ii) Spatial Summation: same sort of thing except instead of doing ligth pinches in the same place one after another, he did 3 light pinches simultaneously but in different places on the dogs paw. the important thing about this is the next cell along the arc is not just getting info from one cell but from lots of different cells. Again one pinch from one cell was not enough to set off the action potential in the next cell but one pinch coming from 3 different cells at the same time was enough to set off the action potential. Again Eccles confirmed spatial Summation. iii) Inhibitory Synapses: When Sherrington pinched the dog vigorously the dog apart from biting Sherington would not only contract its flexor muscle in its leg, it would also relax its extensor muscle. Contraction of the extensor muscle moves the paw away from the body while contraction of the flexor moves the paw toward the body. So in order the paw is withdrawn after the pinch it has to excite the contraction of the flexor muscle and inhibit contraction of the extensor muscle. Again Eccles years later demonstrated the interneurone has an exictatory synapse on the motor neurone of the flexor muscle and a inhibitory synapse on the motor neurone to the extensor muscle. Chemical communication at the synapse One thing Sherington got wrong was he reckoned synaptic transmission was still done by electricity. Otto Loewi (1920) showed this was not the case. He stimulated the vagus nerve to a frogs heart which decreased the heart rate. He then collected the liquid in the heart and transfered it to a second frogs heart and saw a decrease in heart rate. He repeated the experiment only this time stimulating the accelerator nerve to the heart, collecting the fluid and transferring it to a second heart and this time observing an acceleration in heart rate. Loewi reckoned however the nerves were affecting the heart it had to be through chemicals rather than electricity. Important Neurotransmitters The chemicals taking the message from one nerve cell to the next are known as neurotransmitters, below is a schematic diagram of the most important groups of Neurotransmiters Amino Acid Neurotransmitters Glutamate- excitatory GABA (gamma-aminobutyric acid)- inhibitory allow Cl- ions into membrane The neurotransmitters in the vast majority of fast acting,. Directed synapses in the CNS. Monamines Single amino acid Catecholamines- dopamine, norepinephrine, epinephrine (noradrenaline and adrenaline) Dopamine involved with reward centres in the brain Norepinephrine parasmypathetic ns Epinephrine smypathetic ns Indolamines- serotonin Serotonin – mood drugs affecting serotonin include prozac Acetylecholine – efferent neurones at muscle synapses Peptide – endorphins involved with pain centres, naturally occurring analgesics, non natural morphine Soluble Gasses The Structures of the Synapse At the end of the axon is the terminal button, contained within the button is mitochondia, concerned as they are in the cell body of the neurone with breakdown of nutrients to provide energy, their presence indicates synaptic communication is costly in terms of energy. Golgi bodies involved here with packaging up the neurotransmitters as vesicles (small bladders) and microtubules which are involved in transport of certain types of neurotransmitters synthesised by the ribosomes in the cell body of the axon. There many different types of neurotransmitters and we will be looking at these and their different functions in more detail in next weeks lecture. The flat area of the terminal button is known as the pre-synaptic membrane, the corresponding membrane on the dendrite of the adjacent neurone is known as the postsynaptic membrane and between the two is known as the synaptic cleft. The majority of axons terminate at the dendrite of the adjacent cell, more precisely at dendritic spurs - small synaptic buds covering the surface of many dendritesand are known as axodendritic synapses. However there are Axosomatic synapses, located between the axon and cell body, and Axoaxonal synapses, between two axons of adjacent cells and even dendrodendritic synapses between the dendrites of two neurones capable of transferring information in either direction. The different functions of these different types of synapses will be explained later in terms of neural integration. The sequence of chemical events at the synapse i)Synthesis of neurotransmitters As I said earlier cetrain neurotransmitters are made in the cell body or soma of the neurone. These are called Peptides and are made from chains of amino acids are basically short proteins. They are packaged up in vesicles by the Golgi bodies and sent along the axons down the microtubules at the hair raising speeds of between 1 -100mm per day. The majority of neurotransmitters are synthesised in the cytoplasm of the terminal button and from products obtained the diet. Acetylcholine for instance, a common neurotransmitter, is synthesised from choline which abundant in cauliflower, so now you know what to eat before the exams. These smaller transmitters are also packed in vesicles and found with the others around the pre-synaptic membrane. ii) Release of neurotransmitters The release of neurotransmitters is triggered by the arrival at the terminal button of an action potential along the axon. Voltage sensitive Ca ion gates in the presynaptic membrane are opened. When the Calcium ions enter the terminal button the vesicles fuse with the pre-synaptic membrane. The Calcium is believed to be important in the process, following fusion of the vesicles to the membrane, of breaking the vesicle apart and releasing the neurotransmitters into the synaptic cleft. When the vesicle joins with the pre-synaptic membrane it increases the size of the membrane slightly. Obviously if this went on indefinitely you’d have huge terminal buttons, so what happens is at the tip of the button where it meets the axon, some membrane breaks off into the cytoplasm and migrates to the golgi body where it is recycled into more vesicles for neurotransmitters. iii) Action of neurotransmitters on Post Synaptic membrane The neurotransmitter diffuses across the synaptic cleft until it binds with a specific receptor on the post-synaptic membrane. There are two types of receptors a) Ion channel linked receptors and b) G-Protein linked receptors. Once the neurotransmitter binds to an ion-channel receptor, the ion channel will open allowing ions to flow into the membrane. If the ion channel allows Na, sodium in then providing enough channels are open and enough Sodium flows in then the voltage of the cell is made less negative and an action potential is set off running down the axon, such a potential is known as an Excitatory Post Synaptic Potential (EPSP). If on the other hand the channel allows Potassium ions out then the voltage is made more negative making it more difficult for a subsequent action potential to start. This is known as an Inhibitory Post Synaptic Potential (IPSP). The second type of receptor is a G-Protein linked receptor and requires the cell to be expend energy so are also called metabotropic receptors. Binding to one of these receptors results in a sub-unit of the protein breaking away which either directly opens an ion gate or it activates an enzyme in the cell membrane which synthesises a second messenger. Once created the second messenger does one of three things opens an ion channel, directly influences the metabolic rate of the cell or enters the cell nucleus, binds with the DNA thereby influencing the genetic material of the cell. Usually Peptide neurotransmitters are involved with these long lasting changes in cell activity, the other smaller neurotransmitters being only involved with rapid production of EPSP’s or IPSP’s. iv) Reuptake or break down of neurotransmitters The neurotransmitters do not stay attached to the receptors forever, if they did there would be no point in sending any more messages as the postsynaptic potential would be continually firing anyway. There are two ways the neurotransmitters are removed from the receptor, either it is broken down by an enzyme, eg acetylecholine is broken down by acetylcholinesterase, or it is reabsorbed whole by the pre-synaptic membrane, repackaged in vesicles and eventually to be released back into the synaptic cleft when the next Action potential shows up.