SLP RS 102 Topic 2: Synapse PDF

SLP RS 102 TOPIC 2: SYNAPSE OBJECTIVES 1. Explain how an action potential causes neurotransmitter release from the presynaptic terminals. 2. Discuss how excitation of the postsynaptic membrane occurs. 3....

SLP RS 102 TOPIC 2: SYNAPSE OBJECTIVES 1. Explain how an action potential causes neurotransmitter release from the presynaptic terminals. 2. Discuss how excitation of the postsynaptic membrane occurs. 3. Discuss how inhibition of the postsynaptic membrane occurs. 4. Familiarize yourself with the common neurotransmitters. 5. Compare the three different states of a neuron (resting, excited, inhibited) in terms of a. changes in membrane potential in mv b. ions involved and the direction of movement 6. Define EPSP and IPSP. 7. Differentiate EPSPs and IPSPs from an action potential. 8. Define temporal and spatial summation. 9. Describe how action potentials are generated in a neuron from excitation at its soma.. 10. Discuss the role of the axon hillock in the generation of action potentials in a neuron. 11. Compare the excitability of a membrane with a high threshold and with a low threshold. 12. Explain what “facilitated neurons” mean. CONCEPTUAL MAP Watch these YouTube videos https://www.youtube.com/watch?v=L41TYxYUqqs&t=302s The Synapse (7:08 min) Bozeman Science Published on Feb 6, 2017 https://www.youtube.com/watch?v=aDKz3GUVAzg Postsynaptic Potentials (2:35 min) Steven Barnes https://www.youtube.com/watch?v=NUIGGvzLd3g Neuron Neuron Synapses (EPSP vs. IPSP) (11:46 min) Dr. Umar Azizov Published on Apr 11, 2018 https://www.youtube.com/watch?v=ZnC8v9Dl_O4 EPSP & IPSP (2:42 min) Stens Biofeedback Mechanism by Which an Action Potential Causes Transmitter Release from the Presynaptic Terminals-Role of Calcium Ions The membrane of the presynaptic terminal is called the presynaptic membrane. It contains large numbers of voltage-gated calcium channels. When an action potential depolarizes the presynaptic membrane, these calcium channels open and allow large numbers of calcium ions to flow into the terminal. The quantity of transmitter substance that is then released from the terminal into the synaptic cleft is directly related to the number of calcium ions that enter. Excitatory or Inhibitory Receptors in the Postsynaptic Membrane Some postsynaptic receptors, when activated, cause excitation of the postsynaptic neuron, and others cause inhibition. The importance of having inhibitory, as well as excitatory, types of receptors is that this gives an additional dimension to nervous function, allowing restraint of nervous action and excitation. The different molecular and membrane mechanisms used by the different receptors to cause excitation or inhibition include the following. Excitation is achieved through any of the following 1. Opening of sodium channels to allow large numbers of positive electrical charges to flow to the interior of the postsynaptic cell. This raises the intracellular membrane potential in the positive direction up toward the threshold level for excitation. It is by far the most widely used means for causing excitation. 2. Depressed conduction through chloride or potassium channels, or both. This decreases the diffusion of negatively charged chloride ions to the inside of the postsynaptic neuron or decreases the diffusion of positively charged potassium ions to the outside. In either instance, the effect is to make the internal membrane potential more positive than normal, which is excitatory. 3. Various changes in the internal metabolism of the postsynaptic neuron to excite cell activity or, in some instances, to increase the number of excitatory membrane receptors or decrease the number of inhibitory membrane receptors. Inhibition is achieved through any of the following 1. Opening of chloride ion channels through the postsynaptic neuronal membrane. This allows rapid diffusion of negatively charged chloride ions from outside the postsynaptic neuron to the inside, thereby carrying negative charges inward and increasing the negativity inside, which is inhibitory. 2. Increase in conductance of potassium ions out of the neuron. This allows positive ions to diffuse to the exterior, which causes increased negativity inside the neuron; this is inhibitory. 3. Activation of receptor enzymes that inhibit cellular metabolic functions that increase the number of inhibitory synaptic receptors or decrease the number of excitatory receptors. Examples of important small-molecule transmitters Acetylcholine – usually excitatory Norepinephrine – usually excitatory Dopamine – inhibitory Glycine – inhibitory GABA (gamma-aminobutyric acid) – inhibitory Glutamate – excitatory Serotonin – inhibitory to pain Membrane Potentials of the Neuronal Soma The resting membrane potential is always negative. Decreasing the voltage to a less negative value makes the membrane of the neuron more excitable, whereas increasing this voltage to a more negative value makes the neuron less excitable (hyperpolarized). This is the basis for the two modes of function of the neuron-either excitation or inhibition. The concentration differences of the three ions across the neuronal somal membrane that are most important for neuronal function are sodium ions, potassium ions, and chloride ions. There are three states of a neuron possible. A, Resting neuron, with a normal intraneuronal potential of -65 millivolts. B, Neuron in an excited state, with a less negative intraneuronal potential (-45 millivolts) caused by sodium influx. C, Neuron in an inhibited state, with a more negative intraneuronal membrane potential (-70 millivolts) caused by potassium ion efflux, chloride ion influx, or both. When a presynaptic terminal has secreted an excitatory transmitter into the cleft between the terminal and the neuronal somal membrane, that transmitter acts on the membrane excitatory receptor to increase the membrane's permeability to Na+. Because of the large sodium concentration gradient and large electrical negativity inside the neuron, sodium ions diffuse rapidly to the inside of the membrane. (Guyton & Hall, 2011). The rapid influx of positively charged sodium ions to the interior neutralizes part of the negativity of the resting membrane potential. The resting membrane potential has increased in the positive direction from -65 to -45 millivolts. This positive increase in voltage (meaning the potential becomes less negative) above the normal resting neuronal potential-that is, to a less negative value-is called the excitatory postsynaptic potential (or EPSP).If this EPSP rises high enough in the positive direction reaching threshold, it will elicit an action potential in the postsynaptic neuron, thus exciting it. (In this case, the EPSP is +20 millivolts-i.e., 20 millivolts more positive than the resting value.) Always remember: Discharge of a single presynaptic terminal can never increase the neuronal potential from - 65 millivolts all the way up to -45 millivolts. An increase of this magnitude requires simultaneous discharge of many terminals-about 40 to 80 for the usual anterior motor neuron-at the same time (spatial summation) or discharge of the same neuron in rapid succession (temporal summation). This occurs by a process called summation. Spatial summation Temporal summation  (Guyton & Hall, 2011) Excitatory postsynaptic potentials and an action potential. This shows that simultaneous firing of only a few synapses will not cause sufficient summated potential to elicit an action potential. Generation of Action Potentials in the Initial Segment of the Axon Leaving the Neuron-Threshold for Excitation When the EPSP rises high enough in the positive direction, there comes a point at which this initiates an action potential in the neuron (threshold is reached). However, the action potential does not begin adjacent to the excitatory synapses. Instead, it begins at the axon hillock where the axon leaves the neuronal soma. The main reason for this point of origin of the action potential is that the soma has relatively few voltage-gated sodium channels in its membrane which makes it difficult for the EPSP to open the required number of sodium channels to elicit an action potential. Conversely, the membrane of the axon hillock has seven times as great a concentration of voltage-gated sodium channels as does the soma and, therefore, can generate an action potential with much greater ease than can the soma. The EPSP that will elicit an action potential in the axon initial segment is between +10 and +20 millivolts. This is in contrast to the +30 or +40 millivolts or more required on the soma. This shows that at the axon hillock, the membrane is already excitable since it only requires EPSPs of +10 to +20 mv to reach threshold (lower threshold, greater chance to excite and cause action potentials). Compared to the EPSPs of at least +30 or +40 mv to reach threshold at the soma membrane (higher threshold, more difficult to excite and cause action potentials). The threshold for excitation of the neuron is shown to be about -45 millivolts, which is 20 millivolts more positive than the normal resting neuronal potential of -65 millivolts. Electrical Events During Neuronal Inhibition Effect of Inhibitory Synapses on the Postsynaptic Membrane-Inhibitory Postsynaptic Potential 1. The inhibitory synapses open mainly chloride channels, allowing easy influx of chloride ions. 2. Opening potassium channels will allow positively charged potassium ions to move to the exterior, and this will also make the interior membrane potential more negative than usual. Thus, both chloride influx and potassium efflux increase the degree of intracellular negativity, which is called hyperpolarization. This inhibits the neuron because the membrane potential is even more negative than the normal intracellular potential. Therefore, an increase in negativity beyond the normal resting membrane potential level is called an inhibitory postsynaptic potential (IPSP). EXCITATION OF POST-SYNAPTIC MEMBRANE SUMMARY 1. Action potentials (nerve impulse) are generated at the presynaptic membrane and reaches the voltage- gated Ca2+ channels. 2. The voltage-gated calcium channels open and there is an increased permeability to calcium. 3. Calcium enters and causes the presynaptic vesicles containing neurotransmitters to fuse its membranes with the presynaptic membrane. 4. The neurotransmitters are released at the synaptic cleft by exocytosis 5. The neurotransmitters attach to the receptors at the post-synaptic membrane. 6. Ligand-gated sodium channels open, sodium enters.  7. Depolarization occurs. This is the excitatory post-synaptic potential (EPSP). The EPSPs on the post- synaptic membrane usually need to summate for depolarization to reach threshold. If threshold is reached, action potentials are generated at the post-synaptic membrane. 8. The action potentials open the voltage-gated sodium channels, sodium enters. 9. Action potentials spread and the post-synaptic membrane is in an excited state. INHIBITION OF POST-SYNAPTIC MEMBRANE SUMMARY 1. Action potentials are generated at the presynaptic membrane and reaches the voltage-gated Ca2+ channels. 2. The voltage-gated calcium channels open and there is an increased permeability to calcium. 3. Calcium enters and causes the presynaptic vesicles containing neurotransmitters to fuse its membranes with the presynaptic membrane. 4. The neurotransmitters are released at the synaptic cleft by exocytosis 5. The neurotransmitters attach to the receptors at the post-synaptic membrane. 6. Chloride channels open, chloride enters. OR potassium channels open, potassium effluxes 7. Hyperpolarization occurs. This is the inhibitory post-synaptic potential (IPSP) and no action potentials are generated at the post-synaptic membrane. The post-synaptic membrane is in an inhibited state. (Haines, 2006) Presynaptic Inhibition Presynaptic inhibition is caused by release of an inhibitory substance onto the outsides of the presynaptic nerve fibrils before their own endings terminate on the postsynaptic neuron. In most instances, the inhibitory transmitter substance is GABA (gamma-aminobutyric acid). This has a specific effect of opening anion channels, allowing large numbers of chloride ions to diffuse into the terminal fibril. The negative charges of these ions inhibit synaptic transmission because they cancel much of the excitatory effect of the positively charged sodium ions that also enter the terminal fibrils when an action potential arrives. Presynaptic inhibition occurs in many of the sensory pathways in the nervous system. In fact, adjacent sensory nerve fibers often mutually inhibit one another, which minimizes sideways spread and mixing of signals in sensory tracts. "Spatial Summation" in Neurons-Threshold for Firing Excitation of a single presynaptic terminal on the surface of a neuron almost never excites the neuron. The reason for this is that the amount of transmitter substance released by a single terminal to cause an EPSP is usually no greater than 0.5 to 1 millivolt, instead of the 10 to 20 millivolts normally required to reach threshold for excitation. However, many presynaptic terminals are usually stimulated at the same time. Even though these terminals are spread over wide areas of the neuron, their effects can still summate. When the EPSP becomes great enough, the threshold for firing will be reached and an action potential will develop spontaneously in the initial segment of the axon. This effect of summing simultaneous postsynaptic potentials by activating multiple terminals on widely spaced areas of the neuronal membrane is called spatial summation. "Temporal Summation" Caused by Successive Discharges of a Presynaptic Terminal The successive discharges from a single presynaptic terminal, if they occur rapidly enough, can add to one another and "summate." This type of summation is called temporal summation. Not all summations lead to action potentials. Simultaneous Summation of Inhibitory and Excitatory Postsynaptic Potentials If an IPSP is tending to decrease the membrane potential to a more negative value while an EPSP is tending to increase the potential at the same time, these two effects can either completely or partially nullify each other. Thus, if a neuron is being excited by an EPSP, an inhibitory signal from another source can often reduce the postsynaptic potential to less than threshold value for excitation, thus preventing an action potential from happening. "Facilitation" of Neurons Often the summated postsynaptic potential is excitatory but has not risen high enough to reach the threshold for firing by the postsynaptic neuron. When this happens, the neuron is said to be facilitated. That is, its membrane potential is nearer the threshold for firing than normal, but not yet at the firing level. Consequently, another excitatory signal entering the neuron from some other source can then excite the neuron very easily. Diffuse signals in the nervous system often do facilitate large groups of neurons so that they can respond quickly and easily to signals arriving from other sources. Test Yourself Part I True or False. 1. An excitatory post-synaptic potential (EPSP) is not the same as an action potential. 2. Electrical synapses do not involve neurotransmitters unlike chemical synapses. 3. Excitation is caused by opening of the voltage-gated sodium channels. 4. Excitation of motor and sensory neurons involved in reflexes use the small molecule system of transmitters. 5. For excitation to take effect, either the chloride channels or the potassium channels open. 6. If ever potassium channels open, potassium enters the cell. 7. If ever the chloride channels open, chloride ions enter the membrane. 8. Ligand-gated sodium channels are only present in presynaptic membranes. 9. Most of the neural synapses are chemical in nature that use neurotransmitters. 10. The receptors where the neurotransmitters attach are closely associated with the ion channel. 11. Voltage-gated sodium channels should open and allow calcium to enter prior to exocytosis of neurotransmitters.  LEARNING SCENARIO You can easily pick up fine beads using your bare hands and transfer these to a container one by one. With gloves, you hardly feel the beads and have difficulty picking these up. Why is this so? REFERENCES Azizov, U. (2018, April 11). Neuron-Neuron Synapses[Video file]. Retrieved from https://www.youtube.com/watch?v=NUIGGvzLd3g Barnes, S. (2014, August 10). Postsynaptic Potentials[Video file]. Retrieved from https://www.youtube.com/watch?v=aDKz3GUVAzg Bozeman Science. (2017, February 6). The Synapse[Video file]. Retrieved from https://www.youtube.com/watch?v=L41TYxYUqqs&t=302s Guyton, A. & Hall, J. (2011). Central nervous system synapses. Textbook of Medical Physiology, 12th ed., pp 546-557. Saunders Elsevier. Koeppen, B. & Stanton, B. (2008). Berne and Levy Physiology (6th ed., p. 69). Mosby, imprint of Elsevier. Stens Biofeedback. (2017, July 27). EPSP & IPSP[Video file]. Retrieved from https://www.youtube.com/watch?v=ZnC8v9Dl_O4