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Lecture 2

Lecture 2 - BIo271 Synapses.pdf

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Melanie Woodin

Lecture 2 January 17, 20142:51 AM Synapses are the junction point between two neurons. We are talking about the NT crosses over the synaptic clefts. BIO271 Page 1 Electricl--> chemical to electrical again. This is the tranmission. This allows communication between neurons / cell. Synapse: made from pre cursors. The presynaptic terminal which is the The end of the axon. Sometimes called the presynpstic Axon terminal. Full of NT. This is going to release the NT across the synaptic cleft which is the region ebtween 2 cells. Then we have the receiving end which is the post synaptic cell. We are talking about the transmission going in one direction. The pre synaptic --> synaptic cleft--> post synaptic cell There have been lots of investigation of these signals. Motor neuron: neuron coming out of the spinal cord to a msucle. Basic steps of a synaptic transmission. We have the presynaptic cell, synaptic cleft and the postsynaptic cell. The AP comes from the top to the axon terminal. This is where we now convert the electrical signal/AP into the chemical signal. This happens due to a Ca dependent process. Ca is much more [] outside than inside. If you open a voltage gated Ca channel, Ca floods into the cell. Inside the cell neurons keep Ca incredibly low level. Almost non existing in the cytoplasm. Any Ca comes in we can detect the very readily. Infact many proteins inside the neuron the Ca sense it. This means that the synaptic terminal any ca comes in the ca sense it.when the AP comes down and comes to the axon terminal simply replaces the voltage gated Na channels with voltage gated Ca channels. Acts like the Na channels.They are also + charged, more [] outside than inside. So goes in. Ap comes down and reaches a sudden [] of voltage gated Ca channels and then instead of Na, it becomes Ca, Ca comes in and binds to the Ca centered proteins. Their job is to cause the release of synaptic vesicles which are full of NT. They bind to the membrane of the synaptic vesicles, which then comes and dock on the presynaptic membrane. This is also called the actin zone. They undergo exocytosis and then NT is released. this process fof AP comes down--> opens voltage gated Ca channels --> Ca comes in --> releases NT --> NT is diffused into the synaptic cleft, then if its lucky it binds to a recptor or a post synaptic vesicle. This can do that in a number of ways but we can talk about it later. BIO271 Page 2 Intracellular Ca is poor in the pre synpatic release of the NT. The amount of intracellular Ca, ( the subscript is where we are talking about, so "I" means intracellular. ) Intracellular ca [] in the presynaptic terminal is related to the AP frequency. When the AP comes down by itseld it will bind to small complemet voltage gates Ca channels. Going to increase small Ca [] intracellulary vs 100 AP are coming down at the same time. 1 vs 100 hz. These 100 then goes to a much alrger increase in Ca. the amount of Ca we have in the intracellular terminal results in how much NT we release. Small amounts of Ca --> Maybe one vesicle undergoing exxocytosis. 100 AP --> 100 vesicles. We are goint to maintain the indformation…by pulling the AP frequcny in the [] temrinal, and that is going to then cause relative amounts of NT. We also wants to be able detach subsequent AP coming in. so Ca level is maintained very acutely. If we have one AP then Ca floods in and the presynaptic terminal is trying to cleat that Ca out. So when the next AP comes in we can detect the influx of Ca. Ca is like Na. + charged. And the gradient [] is inverted. When we get a high frequency these mechanisms regulate the Ca gets overwhelmed and Ca deals with it. Has two varieties. [] gradient and the electric gradient. These are even higher than for Na. for Eq pot for Ca is above a 100. much higher than the Na potnetial. This tells us that Ca has a verys trong driving force to get inside the cell. Amount of Ca comes in and how much of them trasnitted NT depends on a number of factors, on how well that terminal can regulate and lower the intracellular Ca []that happened because the terminal is full of buffers that buffers the Ca that comes in. Ca is going to pump Ca right back. This can binds to post synaptic vesicles. and at the same time the presynaptic terminals are going to buffer the increase of Ca so the next AP still has a larger gradeint of Ca.when Ca builds up no more gradient of Ca, no more ability to send it to incoming AP. illustrated the synaptic vesicles covered with synaptic proteins. BIO271 Page 3 illustrated the synaptic vesicles covered with synaptic proteins. These proteins helps direct the vesicles to where to go, when to dock and when to exocytose. Large majorities of these proteins that have been identified to existing number of vesicles are sent to the K channels. Ca plays a critical role in maintaining the synaptic vesicles. This is basic overview of the process. Justbe aware of the details in abcde ( starting with A.) The presynaptic terminal, the synaptic cleft is down here. The AP is come from above. There are vesicles located in different regions closer to the active zone. The recycling pools of vesicles filled with NT which can undergo exocytosis to release the contents. And then endocytosis and these vesicles are recycled in the pretsynaptic membrane. These vesicles are recycled in the presynaptic membrane. Ca comes in and then act as some of the proteins that are in the membrane of the synaptic vesicle and that is going to undergo docking and priming. The vesicles are going to come they are going to be physically attached to the active zone through some of the proteins on it. and they are going to be primed for release. Basically means the vesicles ready to release NT. When Ca influx causes exocytosis where the membranes are going to fuse the vesicles with the presynaptic membrane and then spill contents of the vesicle which is the NT into the membrane. Now you need more membranes, and that is called as release site clearance where you are clearing all the transmitter from the region. Then you are going to undergo endocytosis. Basically scooping up part of the membrane again, form vesicles which then gets loaded and return to recycling. This vesicles are going through these processes exocytosis and from a recycling pool, docked and primed, exocytosis are all ca dependent and then exo and endo and refilled back to the recycling BIO271 Page 4 Summary This was heavily studies intitially. Main NT of the neuromuscular junctions. When you move your skeletal parts of the body, you are tighting and Ach is releasesd from motor neurons to your muscles. This is also used in many parts of the brain not just muscles. Important principle: NT has many different functions on the body and the function depends on the receptor. Whether this NT is going to excite or inhibit a postsynaptic region …Is not a property of the NT itself. But depends upon the response of the postsynapse. When you talk about Ach being released, these synapses are called cholinergic. We need to form NT at the presynaptic vesicles. Where the acetyl CoA which is produced by mitochindria, is combined to choline and the enzyme called choline acetyl transferase catalyses this reaction to produce acetylcholine. Ach gets then packaged into vesicles. And undergoes exocytosis where its released into the synapse. We don’t want any NT to be hanging out outside in the cleft for along time. Because when the next AP retained and the NT wouldn’t be able to detect due to the build up of the other NT that was already there. We need mechainsms so that when the NT comes and binds to the receptors, we want to clear it away. So when the next AP we can released the NT and detect. There is a number of ways that happens. 5,6,7. 1)One is diffusion so it can diffuse away but is not highly efficient. 2)the other way is to reuptake the choline and recycle. And put it back into the vesicle. 3)Or we can have enxyme acetyl choline esterase break down. Diff NT’s use diff strategies or combinations of the diff 3 aspects diffusion, reuptake and enzymatic degradation. You can see the enzymatic degradation happens first. Part of the choline is reuptaken and a part of it diffuses away. What doesn’t undergo that process combines to the receptor produces a post synaptic response. This process of deggradation of the NT stays in the synaptic cleft is a major site for pharamceutical development and drug action. If BIO271 Page 5 and a part of it diffuses away. What doesn’t undergo that process combines to the receptor produces a post synaptic response. This process of deggradation of the NT stays in the synaptic cleft is a major site for pharamceutical development and drug action. If someone has a decrease in certain type of NT, and the NT system is not as effective as it should be one strategy is to modify how long the existing transmitter is going to be. Eg: serotonin: important in regulating mood and anxiety. If you have a mood disorder, one stratgey is to ensure that serotionin is kept in the synapse for a longer time for Eg: ddecraeseig the enzymatic degradation for the reuptake which happens in serotonin you can allow the reptake to slow down So now when you release serotonin, which has+ effect on mood, you can keep the effect for longer. This is used in many synapse types in other places in the body to target NT function. This NT itself doesn’t determine what's going to happen. The post synaptic response has specific receptors that neuron expresses. post synaptic neurons has reciprocal recptors for transmitters eg: neuromuscular junction we have Ach receptor which is called nicotinic receptor. Some made odd terms to these recptors. Many diffenr receptors are named because of the outer ligands they activate. This specifical recpor is activated by ach but this can also be activated by nicotine so this is called as nicotinic acetylcholine recptor. When the NT binds the recptor and opens the gate, we are going to increase the permeability of the opst sunaptic memrbane to what ever ions flos to that recptor causing changes in the mem pot in the post synaptic site. Or changes in the mem pot is called graded pot. We talked about graded pot in dendrites. Saw How they create AP. And how they travel down the neurons. See slide. More recptors we have the larger the response. The amount of transmitter that stays in the cleft depends on the number of things. See slide. Synapses shown are isolared by neurons or neuronal muscles and the region os flanked by glial cells which uptake many of the transmitters and put these away. BIO271 Page 6 BIO271 Page 7 Weve being talking about synaptic transmission. There are also electrical synapses. Usually when someone talks about a synapse we can assume theya re talking about a chemical synapse unless they say otherwise. Then it would be an electrical synapse. Electrical synapse is also known as a gap juncion. The major dif between these two, is as we learned in chemical transmission the action potential comes down to an electrical signal and then converts to a chemical signal it used to transmit across the cleft and then produces an electrical signal then. That is different only, electrical synapse where the electrical charge is transferred from directly from one side to the other side because they are physically connected by a protein that makes gap and that is shown here. In this case, we have the presynaptic neuron but instead of releasing transmitter the ions can flow the charge can flow the small molecules can flow directly through this channel which is called gap junction directly to the next. Even things like ca signals can flow directly to the next. This is what it looks like more close up you have this concentrations of gap junctions and the gap junctions are made out of seven proteins that come together in presynaptic side or the post synaptic side. Because they are directly connected the signals can go both ways. Chemical synapses you have it from pre synaptic to the post synaptic. But here depending on the type of protein you can have charges going on in any direction. But each cell that comes I contact produces a set of proteins and altogether they are called connecxins. Connexins are a composition of multiple subunits. They come together to make this structure. And those individual subunits are caled connexins. Plural connexon. Connecxons comes together and forms the channels. BIO271 Page 8 Why would you want an electrical synapse vs a chemical synapse? Chemical synapses are slow because ca2+ has to come in mobilize the vesicle, undergo exocytosis, binding to the postsynaptic cell.. So many steps but electrical signals are can see this in reflex. If you think about rorganisms such as fish who can have their tail quickly when they sense something negative they have a tail reflex. This si mediated by gap junctions. There is a sensory input and activated by gap junctions. If you want a really fast reposnse you can get it through electrical synapse You can moderate chemical synapses but you cant do a lot of chages in eletcrical synapses and they are pretty stagnant. It is hardto modify electrical synapses because the pre synaptic signal is similar to the post synaptic signal so whenever the charge is enetered the post synaptic cell it goes through the gap junction. Same response from the post synaptic cell. When we want to learn something or thinking, this process happens because we are modifying the strength of the synapses. We are either increasing the strength or decreasing the strength. And we are going to find too many for the strength all the time in dif circumstances. This is essential for _____ functions, cognition. Learning and memory so if you are able to modify the synapses, and the signal is same as the pre/pro syaptic cell you wouldnt be able to undergo the complex operations wheras the cheical synapses are modifiable and different in pre pro synapses. But a chemical synapse opens up a repetoire of dif responses you can hve in the post synaptic cell. We can chage the type of receptors in the postsynaptic cell, we can make tailor mode spots for particular option The take home messages there are electrical synapses. Gap junctions Connexons and connexins. Neurotransimitter - we are going to look at major categories and for one example, receptor for ACH BIO271 Page 9 When we talk about chemical synapses there is a big diversity to them. We are going to see that. We will talk about all the types of receptor types there are. It is also important to see that these synapses can be formed in different locations. So we have being talking about a classic example where the axon in terms f the pre synaptic cell ___ under the post synaptic cell. And tht is You have your axon coming to the pre synaptic terminal and then the synapse, dendritic, post synaptic neuron. That is a classic example for the axon forms a presynaptic cell, and synapse form the dentritic cell. Shown in the iamge. But I assume there are dif functions you can find them in many regions of the brain. A very popular one is the axosomatic synapse where the axon is making a synapse on the dendrite. The cell body and soma. This one is actually pretty powerful because you know that when these synapses occur the post synaptic response is a graded potential and that graded potential has to travel all the way down to the axon hillock. And in last lecture that as it travles it decreases with detriment. So the graded pot decreases as it mmoves. So if you have a synapse as far away the time it reaches the axn hillock it is going to be pretty small. But if you make a synapse right into the soma, tyou havea shoerter distance to travel and the chance you are going to the amuntof decrease reduces. O these types play a pretty important role in generating action potentials. Also we have another one called the axoaxonic synapse. Axons are making the synapse onto the axon as well. Pretty rare but when they do occur they havea major effect. So we are trying to generate an action pot here. And this is where the spiking initiation zone. if this is an inhibitory synapse the type that polarizes the membrane it basically always whenever fires is going to prevent that. so it can really control if you can get an action pot or not. But these are not very common. Perhaps more rarely observed are the dendrodentritic synapse. Not gonna talk anyomroe about it. Neuro transmitters are synthesized in the neuron and they are going to be relased at a presynaptic cell following depolarization. The membrane action pot comes doen polarizes the membrane and intiitates the release. Read slide for the rest BIO271 Page 10 Ssome poepl e say 100 some people say less.lot sof debates. But everybody agree on the number of categories. The categories are on slide. AA- we are goin to see GABA Neuropeptides- short straight Biogenic amines ACH - transmitter on its own category. We will talk quite a bit of time talking about this Miscellaneous It used to be thought that neurons release only one neurotransmiter. But we know that is not the case. It is coomon for one neuron to have only one NT but there is no absolute rule. Many neuron types can have one of these categories lets say catecholamine combined with aa. So there are lot of options. What abstracts you need to know the table and what you don’t need to know. Here ar
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