Test II Study Guide
Test II Study Guide NSCI 3310
Popular in Cellular Neuroscience
Joseph Merritt Ramsey
verified elite notetaker
Popular in Neuroscience
This 37 page Study Guide was uploaded by Joseph Merritt Ramsey on Sunday October 11, 2015. The Study Guide belongs to NSCI 3310 at Tulane University taught by Jeffery Tasker in Fall 2015. Since its upload, it has received 190 views. For similar materials see Cellular Neuroscience in Neuroscience at Tulane University.
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Date Created: 10/11/15
September 25 2015 Action Potential Propagation o Conduction of an Action Potential 0 Interplay of Passive and Active Potentials I Action potentials are generated through the balance of active and passive potentials 0 Its propagation begins at the Hillock and ows down to the Terminal 0 This process even occurs in long axons such as projections to spinal cord extending multiple feet I The Hillock is the site for charge aggregation it all sums up on the hillock which is a PASSIVE process 0 Pathway of an Action Potential I 1 Hillock o If the cell is depolarized to threshold it occurs on the Hillock o This is where each the charge from the stimuli aggregates o Passively spreads and collects I 2 Initial Segment 0 Here is where the passive signaling turns into the initial action potential 0 That initial action potential leads to passive spreading and creates the Propagation down the axon I 3 Next Segment 0 The passive spreading from the initial in ux that diffused downstream causes depolarization at the next segment and revitalizes the signal I 4 Regeneration o The process is regenerative so every time the Sodium in ux passively diffuses to the next segment the full Depolarization is revitalized 0 Fires the full potential again I 5 Refractory Period And its In uences o The refractory period of an Action potential prevents current from owing backwards up the cell back to the Soma 0 During the absolute refractory period which occurs as the cell is Repolarizing so Potassium Channels are open and Sodium is Inactivated Sodium cannot enter and thus AP cannot occur 0 Figure A 03911 A in Q l L m l i r L I a 1 x H k Cm 271 quot 39 1 x a Mg V N a 39l ii l li l JEIVk I l 5 f I39 quot1 39l l y 7 pi I V x y I L H r w you A A 3 y e 1J2 nglxxo 7M gt G lt quot mgr1 r all A W l 7 quotHR Ck 0020 R L k K flft39 H I39 39 I Iv riff quot 2 k A quot w7 39 V 4 r l f p J J I O I Iquot 5 amp 39 r gut V l x N 39 Q a A P m U f 3 l Nif kA p m M xx 08 K1 39 woi iquot o Cm J 3 39 I Pun H N a ll i 7 II 0 As you can see in the figure if we were to artificially introduce charge directly in the center of the cell the AP would travel up the cell because no Refractory Period is occurring I This is strictly experimental and does not occur naturally I But this Antidromic Current is useful for tracking neural pathways because the AP occurs in both direction and reveals all I All in all the pathway for AP Propagation is a continual balance of passive and active forces and potentials o Myelination and Action Potentials Moving Down an Axon 0 Figure B 39 a m n ohaa Cl39ll Diquot J 39 x quot quot I 7 7V 7 3 7 l1 lEp AW NO Nam W Ni z 39quot quot quot H V 7 VV r r V LV 39 n 39 39 39 7 H1 39 4r J SHMOE Q bdrm L plrsttfi 0 Note that the AP is sent down the axon because of charge diffusion so there are gaps noted with a as the first depolarization repolarizes and the next channels begin to open 0 Myelination widens those gaps in essence making the signal quotjumpquot between the gaps called Node of Ranvier o Directional Traveling 0 Terms to Know I 1 Orthodromic one direction down the axon in this case I 2 Antidromic backward propagation 0 Back Propagation and its Role I If the Charge aggregate is large enough the passively diffusing forces ow back up into the Soma and into the Dendrites I These dendrites have 1 Channels 2 Neurotransmitters and 3 Synapses 0 These factors can in uence and quotcommunicate withquot other neurons that are upstream to the given cell 0 Axonal Antidromic Propagation vs Back Propagation I Back propagation is possible and vital to proper cell functioning ANTIDROMIC PROPAGATION ON AN AXON IS NOT o Conductivity I Factors 0 1 Myelination 120ms with myelinated neurons 2ms without 0 2 Diameter thicker is better I Duration a short 2miliseconds span I Diameter Overview 0 Larger thicker diameter increases conductivity efficiency 0 Examples 0 C5er Neurons are thin unmyelinated sensory neurons on the skin 0 Touch neurons are generally myelinated for quicker response 0 Pain receptors are thin and unmyelinated the re ex occurs before the realization o Conduction 0 Factors In uencing diameter and myelin presence 0 Glia Cells and Their Roles I Oligodendrocytes in the CNS Central Nervous System one wraps its extensions around numerous neurons in the CNS I Schwann Cells in the PNS Peripheral Nervous System each cell anchors itself to an axon section and produces myelin o Myelin I Figure C 7 a w 391 nr lrr39 r39 u n l a It separated inner and outer charges normally they rest right on the membrane but with Myelin the charges are more separated They no longer collect and congregate on the whole membrane but instead on the nodes September 28 2015 Propagation Continued o Saltatory Conduction o Axon Image Figure A li x a Q1 HUM orquot0 Q h P1VLL 3RJ quot 39i 39 39quot39391 12 M r 39 quot WW 39IC LWEM r T 39 A JC rquot 3quot 4 xwff Hul t 4 l 1w a Elam Y l I 192 i 7 1 4 a 1 r k x 7 74 quotquot Now 3 fr 39 We have a decreased A Number and B Accessibility to channels in the internode space 0 This myelination creates a strong Capacitance I The potential to store charge I An electrical machine idea Figure B we MN l39mtif mcc l f l xixxv I nkltquot39 UK fl LU qu Y w ltt pumpquot I ffquot l l le Mom 0 Presents a similar picture as the membrane in a neuron o The myelin portion correlates to the interspace 0 Charge diffuses rapidly only interacting at the plates or nodes for the neuron o Internode Interaction I Action Potential Generated and Regenerated at each Node Sped up and Propagated at each Internode 0 There is a very small amount of charge interaction and interference at the internode 0 Because of this the charge is kicked out and propagated rapidly ion diffusion is incredibly fast 0 But at the nodes we have normal channel levels 0 So the charge collects and interferes with the propagation 0 That s where the charge diffusion occurs into the axon initiating another AP I Passive Diffusion that occurs is incredibly rapid both 0 1 Moving over the internodes o 2 Moving down the neuron o DeMyelinating Diseases 0 These diseases dramatically slow the normal functioning of the human body I 1 Multiple Sclerosis MS CNS I 2 Guillan Barre Disease PNS Passive Properties 0 How is Passive Charge Conducted 0 Consider these three properties I 1 Membrane Capacitance I 2 Membrane Resistance So inherently Conductance I 3 Axial Resistance 0 Active and Passive Interplay 0 Active Potential is always the same size an allornone response I Axonal occurring through propagation and regeneration recharges so to say 0 Synaptic Potential is different diffusing throughout the cell J I A received stimulus causes a cellular response I That stimulus multiple stimuli spread from dendrites point of stimulus into the Soma where they aggregate o The Two Together Figure C quot Md lilony Jimuh m0 gmmct ouch Hex H Howww l rlli u ulu l D o l N W r UHl V J V I J A I A 39 MWQ Polmhm 39 Bj39 miwulm j chtk f C Mk Sumpl it Oxlluslm w 1 1 ca cl 3 0 W l d l l39 139 I Notice the charge readings for the Axon always and consistently the same 9 ACTIVE I Notice the arrows on the right however the dendritic stimuli are not strong but they combine in the Soma 9 PASSIVE 0 Important Properties 0 1 Membrane Capacitance charge accumulation on the membrane I Denoted at Cm Measured in Farads I Surface area of the axon increases Conductance o 2 Membrane Resistance the membrane s resistance to ow running through I Denoted Rm Measured in Ohms Q I This is a function of the channel probabilities 0 And is therefore inversely and proportionately related to Conductance g o 3 Axial Resistance the resistance present in the axonal cytoplasm I Denoted Ra Measured in Ohms Q o The Membrane Circuit 0 Components I 1 Capacitor Membrane Capacitance 0 Stores charge I 2 Resistor Membrane Resistance 0 Determined by Leak Channels I 3 Battery Membrane Potential 0 Leak Channels determine Resistance Conductance o Capacitor Holds the charge 0 Membrane Current 1M Capacitator Current 1c Ionic Current lion 0 Ohm s Law 0 Measures the magnitude of PASSIVE MEMBRANE POTENTIAL response Membrane Potential V I x R Membrane Current x Total Resistance therefore AV RAI 0 Figure E l gj39vltcquot V U lL wQI V I39Llll ljZKLU39V J Qk kj sv M glad1 5 1 J 9U l LL I P rl Ifl quot J 39 haw 39 f d quot Hm I 394 C K E r 0 3 quot quot3 HE ma quotnlxoctwwq I quot3 I0quotqc d0 39lt I d s panho39ulc Cumm 4 Ilm39xskmcc oI39NcthnQ I gimbb WM quotlic U IM r NIH in n J NCU C Pquot quot I quot WIIQVE Ifquot I39Yf 0 w l39139ju1 W vi 39 pg 2 m 0 39 3 l I AUX Ognv AV Kl M5 Mu I g 4 0 punk 0 ifaom R I li f io 7quot W Y 9 9h 1 L I Notice the linear proportionality of the charges 0 This proportionality is based on Ohm s Law I Dependent on a constant value for quotRquot Resistance which is typical and makes sense 0 So if R changes Resistance then everything changes 0 Consider the potential of R to change based on Channels interactions and responses R can shift I But for Passive Interactions Constant Channel state considering they are voltage gated Ohm s Law tells us the Potential and the magnitude of the cell s response 0 Strictly a review of Passive Interactions 0 Kinetics of Membrane Potential Response to Current Flow 0 Membrane Time Constant I speedrate of charging and discharging curren t for the cell I In essence how quickly does the cell respond to current changes and how does the speed of that response affect its function 4 I Dependent on Resistance if the resistance is high recharging won t occur quickly and Capacitance a high potential to store charge is easier to recharge o Designated as the Measure of Time I 1 To Charge to 63 Of Maximun I 2 Or to Discharge back to 37 So a 63 drop if at maximum action potential firing 0 Rate of Change is a Function of I Membrane Resistance I Membrane Capacitance o FigureF 39L quotIL quotquotl Jl quotJ 39 LAM1r J N J J39 0 I p Hl nanit ll m Eolmilol quot quot quot 7 x aquotl A rquot J coo16d Am 1r quotL39 momma I luvq ow I W H 59 lf amp A t VJ O gtO Ll 1393 lLl l1 gtM mayquot C1lttoiqu I am iiCCUC AP AIHMH mnml odd i 3m WE r I t LUle m J U f f SEW L x I Notice that with a small T the membrane recharges quickly making it very difficult for oncoming stimuli to aggregate and create and Action Potential Left Side I With a large T however the response time for recharging is slow and elongated allowing successive stimuli to add on the neuron and potentially cause an Action Potential Right Side September 30 2015 Passive Properties Continued 0 Idea of an RC Circuit Series 0 Cellular Comparison 0 Components in a Circuit I Capacitor stores the charge has the potential Intermembrane Charge Storage in Neuron I Resistor conducts the charge Channels in Neurons 0 Figure A xh IL Aquot til L k39l 139 FL quot IV MH quot h39lluquot quotquotl M Tquot 39 quot 4 1 a J 1 u v Luau m 39ra39i f 1 w i 2 L I txn ulwm msvwl L39tb U r hj C n T t K l l1 k N L a l l l 2 c hh gwc1397Uxa3 x39t H lUWC 39 1 x V l R j l 33th ll J f ws ll L WW I Ann39xf c 39 AALx 139 l N x Jdvk M A a MK uL Ci L J L l l C quotquotquotquot a u b d W don t in I g 39 l a W Gilcount 1v 5s m UH Ul wax quot LukUH MW Jot u J W43 m u past 1 39 8 f I r quot ii 39 f V1quot v r 7 a 3 l b J x quot Em r 3ucmsgn c tom low 1 as R polox ah q I We see the display in a Circuit View Part A o Cm Membrane Capacitance 0 Decreases at each segment because some will naturally diffuse out o rm Membrane Resistance 0 Contributes to how much ows out through the membrane 0 Fa Axial Resistance 0 Contributes to how much ows out based on axial properties And the Cellular mV View Part B 0 Figure B V ZW Imam 107le I mu7 x cu 4 l W Q J a 39le Cmul n mommt ow quot I And then we have a simple visual of what is at work within the cell the charge as the current travels down the cell passively decreases at each part 0 This leads to the idea comparable to that of T I T dealt with passive charge degeneration over TIME focused on a single point in space I But now we have A dealing with passive charge degeneration over DISTANCE time is not regarded at all in this case 0 A Membrane Length Constant 0 Only has two factors in uencing its value I 1 Axial Resistance ra I 2 Membrane Resistance rm 0 Expressed as 1 rm Ya I So from this equation we can see the relationship 0 The higher the rm Membrane Resistance the farther down the charge can travel because the Membrane is more resistant to charge escaping I So the larger the Length Constant A the farther the Current can travel without decaying too much 0 Figure C 39I1Hi1b WTHWubuwuwt NU Hwy A algvxou a A s tx deq w DbA70 93 lod CmO DHNC h M 0m mag disinoccgt mmmmawt awwwn 1 J VICMVE C Similar to Tao the Length Constant is a measure of The DISTANCE the current takes to decay by 63 or down to 37 of each initial measurement 37 of the maximum is considered the distance similar to Tao 0 Figure D l oovo An EXPOWGWllQl lt1th CCUt 3 ohle m G mm Uta Mm 39 m 39 H GLUZE o 7 quot 90qu Physiological Impact of Lambda 0 FigureE ionic as um I 35 Ir If M mm I 4 ON 4 6 3 TM ml H39ulOJL 9044511quot lowlnhc h ltTMquotgtC1 l LCHQC 93A L1H 391 WW wY H W Ilmt e b l w 1 J c 1L Cells mm H 2 3 1 l1 CjH C39ClClb L Notice that the initial stimuli are equivalent the Presynaptic Cell produces the same response on the dendrites of two separate cells I But by the time the signals arrive to the Axon Hillock the different A values result in different charges being present 0 Test Examples 0 1 We have a 1mm A and need to get this particular cell to 55th0 reach threshold If we give the cell a 10chharge 1mm away from the hillock will an action potential occur I By the time the cell reaches the hillock it will have gone the distance of the Distance Constant and will therefore have decayed by 63 So the value is 37 of what it began with or 37mV I Recall that we need to rest at 60mV so we need a depolarizing effect of SmV I 37mV is not large enough reach threshold 50mV needed 2 The above scenario remains true except now we give the cell a 10chharge on two separate dendritic extensions simultaneously Will and AP occur now I Now we use the same math and simply add the charges as they aggregate at the Hillock I 2 x 37 74 which is enough to reach threshold and cause an AP 3 In this scenario we have two separate dendritic extensions upon which we induce a 10chharge each of which are 1 A away from the Hillock Each extension also has an equivalent time constant given as T This time we induce a charge and wait one 139 to induce the next Will we have enough charge to induce an AP I So here we have two charges at two separate times but each at lOmV I The math is the same for our Length Constant by the time the first reaches the Hillock it measures at 37mV I The same is true of the second charge by the time is reaches the Hillock it also 37mV I So now we must consider time o For the second current it is irrelevant as soon as it arrives it s a 37mV and combining with the First 0 For the first however we must consider the Time Constant One time Constant later the charge that we began with at time t 0 will have decreased by 63 so will equal 37 of what we began with o In this instance we began with 37mV so applying the 37 we now have a current of 13mV I Adding that to the 37 we have exactly 50mV enough to cause an AP Synaptic Transmission 0 Intro 0 Types of Synapses I 1 Electrical I 2 Chemical 0 Electrical Overview M It s a direct passive connection allowing ow to occur directly between synapses Electronic Coupled The passive spread of the current or charge Current can directly ow between the two Incredibly rapid 0 Chemical Overview I Much slower not as immediate of an effect No direct transmission of charge occurs The Chemical neurotransmitter must go through Vesicle Secretion and then Bind to the postsynaptic portion and then the charge is initiated All of the binding and opening and interactions occur in the synaptic cleft Gap Iunctions Electrical 0 Two HalfChannels I FigureF 39J M WowK lxci1ctr new 1 K W p j fq vhxptux we optx w lg l0 ltl 39 ail4 quot BK lClllY Uleulg 0mm W up lushwm LC a q39l no law ltisLntme 39 39 39l I133 WWCulxsollctled DEBll u39 10m These half cells are called Connexons o Connexons are made of Connexins The HalfChannels are known as HemiChannelsquot Pre and Post Synapse Cells contribute a half 0 Concept of quotPrequot and quotPostquot Signal Cells I This is determined merely by the origin of the signal Neurons always have a Pre Axon and Post Dendrite or Body site But Gap Iunctions don t really just a mix and ow ad interaction of charges 0 Allows for synchronized and rapid response I All connected cells are affected Kind of like one long extended cell that can interact together 0 Affects gap Iunctions I 1 pH and Specific Ions 2 But They are almost always open I 3 Charge ows by the gradient present because the ow is free and open This trait means that all cells will be affected 0 Chemical vs Electrical 0 FigureG 39 I I quot inf Il4lpl I 5 3 PW I quot I f Cl Ln m 39 39V V s quotll Iquot r 39 I l 1 I The current spreads passively but there are two passive points of travel 0 1 Through the cell Axial Resistance 0 2 Through the HemiChannels Gap Iunction Resistance 0 These channels increase resistance I This displayed resistance difference is expressed as The Coupling Coefficient o Described as the Ration of Postsynaptic Response to Presynaptic Response 0 PostPre o It is a function of the number of Gap Iunction Channels 0 More Greater Coefficient 0 Fewer Smaller Coefficient October 2 2015 Synaptic Transmission Continued 0 Coupling Coefficient 0 Electronic Coupling I FigureA n I U A L 39 l mid A7 J Voltage vecoudcd m A 0 C qc 1cm ltd iv 7 j P I lr tliht mm39oem S WS M39SLquot o B KNU I in N3XRCP A 0 With this number we can induce the relative frequency of channels present at the Gap Iunction more channels means closer number to 1 0 Chemical Signals 0 Figure B llml mutloko H1 39 UK 3 Mn m KL JJNAXL 2 u mplC llL I ll PCltMIquotquot llu kl39 nlmp 4 0qu WI 0 t 0 Ca C llx NC I 3 l 11 aimp l lf39 mfm 39uL w l 9 l 339 I 0 W3quot quot5 39l U l39iL lU W C l39lx WK J tJLIuolCI39 1Miler L b39m 9 glow r N I W8 ilezL HCA quotJ x s Quid or gm WW d V Wfklv lCIKC 0M 5 393 7 x EXOFJ l39JJ x mung N x 3 quot 4 39jxI39lpno lm as 39 Ih39v mu xGUim 04ch 3 H xixL ei rq uc girmr l lo up w VJLlQiVClIl It can he E PS P and IVS 3 I 1 Presynaptic Neuron 0 AP Causes Depolarization o Depolarization A ects Voltage Gated Calcium Channels 0 Calcium In ux Leads to Calcium Binding to Neurotransmitter Vesicles leading to Exocytosis I 2 Post Synaptic Neuron 0 Has Specific Neurotransmitter Receptors on the Membrane o The NeurotransmitterReceptor Complex Leads to Channels Opening Which can Cause EPSP Excitatory Post Synaptic Potential or an IPSP Inhibitory Post Synaptic Potential I 3 Glial Cells Astrocytes o Neurotransmitter Cannot Sit in the Cleft it Needs to Be Taken Back or the Signal Will Keep Turning 0n and O o Astrocytes Run the Process Called Reuptake o Ohm s Law I V IR I Consider Resistance 0 At rest only the Leak Channels are open to resistance is relatively high But if we change the resistance ie affect the channels we change the excitability 0 Changing Resistance Changes quotrquot in Ohm s Law Decreased o Decreased quotrquot means decreased quotVquot which means a more positive value altering excitability remember to consider I the charge coming in as well So V Potential for the currents changes 0 We also see a Current Created De Hyper Polarization Occurs 0 Figure C Relation of Chemical Synapses to Electrical Signals A j P 39 1 l7l i quotlquotll A I quot quot I a I Tull THAN l c Ibelggmpm kg 39 l d A Tquot l Hewitt 39 Iquot quot 3 92 L L lquot l 1 Cl m quot w Notice the response can be Inhibitory eg Potassium Flow Positive Current or Excitatory eg Sodium Flow Negative Current 0 Synaptic Types 0 They all vary based on location within the body and type of neuron I 1 Axodendritic Synapse 0 Can be on two parts of a Dendrite o I Dendritic Spine generally excitatory so Glutamate is used 11 Dendritic Shaft generally inhibitory so GABA is used The functioning of GABA and Glutamate display the common and extremely frequent use of these two Neurotransmitters 0 They Modulate all bodily actions other neuropeptides are merely secondary tweaking and regulating Inhibitory or Excitatory responses here and there Inhibitory Axodendritic Synapses Shaft are more Proximal to the Soma than Excitatory Spines 2 Axosomatic Synapse O O o Directly onto the Soma almost always inhibitory 0 These synapses are more powerful at controlling Neural Response than the Axodendritic Synapses 0 Their proximal location to the Soma means there is more direct control 0 On top of the fact that inhibitory synapses have more control You also can t have only one excitatory synapse that has the capacity to induce an Action Potential I Except in the Neuromuscular junction where is fact is true I 3 Axoaxonic Synapse o Axon is Synapsing on another Axon 0 Always occurs at the Axon Terminal not on the Axon Extension 0 The other to synapse types affect and in uence AP Generation Through EPSP and IPSP s 0 They can accomplish this because each occurs upstream before the AP actually occurs 0 But the Axoaxonic is different 0 Axoaxonic synapse in uences neurotransmitters that are present 0 Occurs downstream so it makes logical sense in the cascade of a neuron AP 0 How does it affect Neurotransmitters o 1 Alters Membrane Potential Which affect calcium gates and vesicle release 0 2 Alters intercellular machinery on the synapse o Synaptic Classes 0 Asymmetric vs Symmetric I Figure D 39J 39 W quot w U n itWhi All C o Differentiated by the Postsynaptic Protein Density 0 EPSP s and IPSP s 0 Individual Considerations I Excitatory PostSynaptic Potential I Inhibitory Post Synaptic Potential 0 While the above descriptions describe the individual effects of an EPSP or IPSP the actual functioning of a neuron involves their interaction integration and summation which ultimately affect if an Action Potential Occurs 0 Calcium Dependent Exocytosis o How is the Neurotransmitter even released 0 1960 s Experiment I Used a voltage clamp to measure to record membrane current the cell s response 0 So they recorded the AV under the clamp the change in potential was equal to the membrane current The EPSP I They then began blocking channels and inducing current 0 1 Sodium the blocked channel had no effect on EPSP in Post synaptic cell 0 The provided current still induced the opening of channels 0 2 Calcium EPSP no longer occurred it was contingent on the calcium channels for Neurotransmitter release and subsequent EPSP October 5 2015 Synaptic Transmission Continued 0 Continuing on Calcium Dependence From October 2 0 Figure A shows the current recordings from the experiment revealing Calcium s importance I Blocking calcium channels blocks the ability for the post synaptic cell to produce an AP I The Calcium dependent membrane depolarization is what allows for neurotransmitter release and Postsynaptic Action Potential 0 But the Neurotransmitter Release IS NOT voltage dependent it is a CALCIUM DEPENDENT process through exocytosis o Exocytotic Proteins Figure B f i39quot r vmvn 39 v Wt f fch r am 1 3 396 n t39 239 L f N V v A c Fall mm a k z Jl quot 39 J I a CI 39 7 lf 391 l hquot Li W W quotw law 1 iv r3 CU Izr 1 flUH lCl l LNCR quotk WC 9 Lock pita too to lbw H 3 l V J I The proteins are called quotSnaresquot the membrane and vesicle proteins that interact with each other not Synaptotagmin which interacts with Clacium o Vesicle Snares o SNAP 25 o Syntaxin o Membrane Snares o Synaptobrevin I Calcium Binds to spot on Synaptotagmin causing a conformational change in the protein which binds the vesicle and the membrane together 0 This allows the phospholipids to interact Vesicle Cycle 0 As the vesicles are released terminal surface area changes so there must be a constant cycle recycling the Phospholipids o The Cycle Figure C I 1 Storage Pool 0 The vesicles are stored and held together by the Protein Synpasin 0 They are eventually moved down the Terminal by Calcium Dependent Processes I 2 Readily Releasable Pool 0 Priming Occurs to release can happen 0 SNAP proteins mediate the priming I 3 Fusion Pool 0 SNARE proteins mediate the fusion of the vesicle to the Plasma Membrane I 4 BuddingEndocytotic Pool 0 Clathrin begins the budding process for Endocytotic Vesicles to Crow 0 Dynamin clips the vesicles from the membrane 0 With the constant increase of surface area we observe an increase in Cell Capacitance Capacitance is a function of Surface Area I This increase gives rise to more stored charge which changes the properties of the cell I So to balance the constant increase in Surface Area endocytosis must occur o The rate of endocytosis in the axon terminal is a function of exocytosis of Synaptic Vesicles o Quanta Release 0 Neurotransmitters are released in specific Quanta 0 Experiment performed in Motor Neuron Endplate A Specified Name for 0 Motor Neuron Synapse I The Axon is stimulated and the Endplate Potentials EPP are Recorded I The Findings 0 1 We Find Miniature Endplate Potentials 0 These occur upon the release of a single vesicle of Neurotransmitter 0 Small random blips in the EPP Recordings 0 2 Most Small Artificial Stimulations Fail To Produce a Response 0 When we began to input charge into the Endplate most of them never resulted in a response change in EPP I This is because chemicals were present to inhibit in an attempt to isolate a unitary response I So the Release Probability was decreased the probability of a response is a function of release probability 0 But the times there were multiple responses the superimposed responses were found to aggregate the response was added 0 Also found I A Numerous Failures I B Occasional Minis minis are always spontaneous o 3 By Observing the Invoked Stimuli these aggregate for their voltage recording and the Minis we Observe a Quantum value for Neurotransmitters 0 We see that the smallest invoked response and the minis result in equal EPP values peak at the same levels 0 The spontaneous responses Minis always fall within 35mV o In Induced Responses we see peaks at multiples of 4 0 Figure D Measuring the Frequency of Induced Responses Number of Induced Responses on YAxis mVof Response on XAxis I 39 l 39I u g 4 l I 39E U H l3939 l l 39 I I 1 l 39 l x hll ll H 39 I lily l l lull lquot ill ll v lJl 1 l 39 l 391 H K ID39II 13I 5lk II 39IIII I All I Iquot 1 I rm f s I l l 39 W I mu m Ir Hi i g 39 ml I l l lquot I lid 1 Fill391 quotJl k l l I I I7 Ii II l 39 I f quotE 39v l l I I I I l I l I I I I r I l l 39 I V quot Ijk L quot L J ll 39 l I l l I II39 l quot quot 7 I I I l I L um I uI I 39quot I I I 39 A 39 I 39 I D 4 L1 si39 l a kc I ll dlt39 l2 Ik39 lgquot IC39 I quotq f 9 1x 39 Li l quot l I H ZIIL IJII ILllllMQC l Hat LI39I o lltsl Iyqui 4 mV I We see the congregation of potentials at particular values this reveals the Quantum Value of 04m V per Vesicle of Transmitter 0 These are seen as a series of Peaks in the Data representing multiple of the smallest unit 0 All a multiple of 4mV o Reveals the constant level at which Neurotransmitter values are packed in the Terminal they induce the same response 0 So for more PolarizingDePolarizing Stimuli it is caused because of the NUMBER OF VESICLES not the AMOUNT OF NEUROTRANSMITTER I What causes the Variability in the Curves in Between the Quantum Values o 1 Faulty vesicle timing 0 2 Random Diffusion and Interaction with Receptors o 3 Receptor are Affected By Membrane Properties I But the More Vesicles that are present decreases variability I Threshold Mathematics 0 Say we need to depolarize the cell by 20mv standard number how many vesicles would it take o 50 vesicles at 4mV per Vesicle would Depolarize the Cell by ZOmV o This Quanta Amount Became Known as the Unitary Response it is standard 0 EPSP and IPSP Generation 0 The same concept and idea of the EPP on a Motor Endplate I Neurotransmitters have specific Quanta 0 But we also see that each type of synapse has its own type of Neurotransmitter I Motor Inhibitory Does not exist I Motor Excitatory Acetylcholine I Neural Inhibitory GABA I Neural Excitatory Glutamate I Other Inhibitory Glycine 0n Spinal Cord and Retina o Inhibitory Potentials are produced by an outward current which is mediated by Chlorine I Outward current produces Hyperpolarization in the Cell October 7 2015 Synaptic Transmission The Postsynaptic Perspective 0 Chemical Synapse Receptors 0 Types of Synapse Receptors I 1 Ionotropic o Ligand Gated has a specific domain on the protein for ligand binding 0 Causes a conformational change 0 The 13 Domain and the 23 Channel are all part of the same protein complex 0 It is Tropic for Ions it directly mediates ion ow I 2 Metabotropic o GProtein Coupled Channel 0 Signaling cascade activates response leads to 2nd Messenger 0 It is a 7 Spanning Membrane Protein 0 Voltage Gated Receptors and Channels were vital to Neurotransmitter Release these types of Ligand Induced receptors and Channels are vital to NeurotransmitterAcceptance o Neurotransmitter Receptors o Neurotransmitters have the ability to bind on various types of Receptors I Most often they can bind on a fast acting Ionotropic as well as a Slow Acting Metabotropic GProtein I Some Examples 0 1 Catacholamines only bind to Metabotropic Receptors o 2 Glutamate GABA Acetylcholine all have both 0 Acetylcholine Example I Acetylcholine is an Endogenous Agonistic Ligand 0 Figure A o Curare Nicotinic o Atropine Muscarinic r irr Iifj39fljf 7quot l Jll I gt A f x 39439 r 1quot 39 Xl I f r r 17 z T A it l39v39 l II L H k l l I But Antagonistic Ligands play a role as well 0 1 They can bind to the receptor and block the binding site 0 2 Or they can cause a conformational change that drastically reduces a inity for the transmitter The antagonistic ligands inhibit proper Endplate functioning so they inhibit muscular use curare is a paralytic o Neuromuscular Iunction Endplate o Diagrams I Figure B o Neuromuscular Junction is Innervated directly on the Muscle Fiber 39 39 39 j39 quot39 39 7 I II Hi 11 s 39 m I 1 r39 v 39 ill 539quot Nat UH My 7 r 1 a f it V lquot l i l l 39quot 397 4 J rrquotquot39 I r r a t f 1r l u f i l I I Figure C o Synaptic Boutons are the places of Axon Terminal innervation o The receptor is always Nicotinic and Ionotropic for an Endplate 0 We also see the Endplate defined x i l 14 l l j 1 U A r 7 39 I 1 l 0 l l quotI 39 l 1 quot lllL 11 x39Jl Kl n l f f lq J l3f 1 tgtL2 39 quotwill 1 quot 1Lziquot 1q otfh 39l N LLJH MC a r quotfquot 39lquotr wk 391 7 Mira p V quot 4 391 H 39b I gt J 31 1 W a T I I 39 x J 19 for U LU 1 4 mi nd a In n39f i Y ig j 39n ll 139 K V lulu 1 7 I Figure D o Vesicles o Mitochondria o Myelin Sheath Schwann Cells 0 Basement Membrane contains Acetycholinase that breaks down Acetylcholine into Choline and Acetate 0 Has numerous Iunctional Folds T 39 39 3939 H quotuquot u39 397quot i quotquot fl 3 V I p E Iy x 39 1 xquot Lillll39l0ftl139l I Q w l f 0155quot 39 1 gill ail link 391LJT LTquotk739H quotDEM 2 quotwhiff I Q quot 1 quot I 31 quot K5 1 lHQQKWW Kl 5 fl quot 1l N l We 1 r WrJf395quot lt u5quotlt forelmWC C l l 2 quot 391quot l 39I I llquot Ru39quot0quotquot if i i3977l t 1 l l Clfl fl 3939s vi WI quot 1 KlLV vun wom t ti ab WUl7 to Y C 1049 CL ii 1101 WC mmmic v M mhxichd Vt x m w w J M I mm x a c 1 r it 0 Random Occurrences along the Endplate are called Minis o Nicotinic Receptors 0 Extremely important aspect of Acetylcholine Effect on the body 0 Components I 1 Two a Sub Units 0 2 Alpha Units are always present for Nicotinic receptors 0 This is the site where AcH binds requires two to bind I 2 At Least One Y Sub Unit I 3 At Least One 8 Sub Unit 0 Figure E 4 mm m it lquott quot 39 l v x q quot 7quot A 39 RAJ quotl K 2 4 xi a quot 39I I 39 l rquotx 39339 039quot ii 39 L f 1quot Liltquot390 11 C U quotI L WY 39 l 39 quot 39IJl ll39lquotquot f l c 13quot 31 393 lquot 39L k s 39 g L39 l I 39 39C39 39 39 jfjrvll39lrf 411 C quotLLquot I my 39 f l 339 39f 4 39 w I I J F ill lJ l 1 l r u l I l l lA L f n A a l 6 l L x gt l l l I 4 f 2 l 39l J l I l l l quot r I ll J V k 5 In l I A o Acetylcholine induced opening I Sodium and Potassium can pass through the channel I But consider Driving Force Sodium will rush in much faster than Potassium rushes out I So we see a depolarization that occurs in the Post Synaptic Cell I So EPP End Plate Potential is excitatory in response to an Action Potential 0 Nicotinic Channel Currents Recorded Through Patch Clamp I Figure F 0 We observe an inward current Negative Current Depolarization 0 We also see they re all square so a particular amount of charge is produced because of the channel 0 These charges sum I l Iquot i if llil 1 l g u r l f k LI v r Jr liequot l 1 t 39 iquot m ll iquotquot Ui k 1Nw39wi ii v 1 39 1r quotquotw I wit quotquotlv l I i u r l l 39L l 4 k gtl l1k l lJ Il l I ll 0 EPP Reversal Potential 0 So we know this involves 13 The Binding of Acetylcholine 23 A Nicotinic Receptor and 33 Potassium and Sodium Ion Flow I So at what point does the Current Peak and switch directions I What are the current properties associated with an open nicotinic Channel I When does the High Driving Force of Sodium weaken and reverse 0 To record we Need I 1 Open Nicotinic Channel I 2 Control of the Membrane Potential Vm 0 Searching For Vrev 39 lNa 1K 9 1m lout I Experimentally Determined the Vrev OmV 0 Diagram Figure G I The channel is more permeable to Sodium so the Reverse Potential is not quite at the Theoretical Value I EPC EndPlate Current I EPP EndPlate Potential 1 ll 1 U1 r L 1 H r n K l I 39 1 l r 39Tt r i 39 w t M 1 1 39 l 39ltlll39l quot 1 jl 44 Li 1 o39c 1 7 3 i I 39 vii 39x I 39 F l l I it l39m V 39 l quotllquotin ll llquot I J 397quotlt 39 lquot H Unix 1 u V l I4 139 I 1139Il llz Pl L L ar f 0 Consider the Driving Force of Each Particularly How it Progresses as the Channel Remains Open I Driving Force Vm Vion I So consider Vm as it grows more positive Potassium continues to rush out and does so even more 0 violently because the Potential is drifting away from the Ion Potential 0 So the Driving Force is growing 0 Meanwhile Sodium Driving Force begins to slow down 0 Eventually when the cell is so positive Sodium Gains a small Positive Driving Force So it no longer ows in So consider Vm as it grows more negative Sodium continues to rush in and does so even more violently 0 because the Potential is drifting away from the Ion Potential 0 So the Driving Force is growing 0 Meanwhile Potassium Driving Force begins to slow down it began with a large outward hyperpolarizing positive ow 0 Eventually when the cell is so negative Potassium Gains a small Negative Driving Force So it no longer ows out and begins to ow in 0 So in the Diagram to understand the current and potential interactions we must understand and consider I 1 EPP I 2 EPC I 3 Single Channel Current I 4 Transmitter Gated Channel Response I 5 Resting Channel Response 0 In those considerations we take into account the Resting Channels response I The cell must get back to resting potential in response to the large change in Potential I It accomplishes this in part through the resting channels which are constantly working to counteract the Nicotinic Channel e ects October 9 2015 Synaptic Transmission The Postsynaptic Perspective Continued 0 EPSP o Glutamate Use 0 3 Types of Glutamate Receptors so Excitatory Receptors in the Nervous System EPSP I 1 AMPA I 2 Kainate I 3 NMDA o The receptors are named because of their Agonists o AMPA and Kainate 0 Very similar to Nicotinic receptors as far as current and ow are concerned 0 Glutamate Binds and causes Sodium and Potassium ow I Sodium rushes in faster 120mV Driving Force than potassium ows out ZOmV DF 0 AMPA and Kainate are purely Ligand Sensitive I NMDA also has voltage considerations 0 Reversal Potential for AMPA and Kainate I Like Nicotinic Receptor these have a Vrev OmV I The reversal potential was studied through the peripheral neurons and spinal cord connections specifically looking at a re ex motor neuron o For this specific type of synapse we have almost entirely AMPA receptor but it acts the same as Kainate I In the experiment they observed o 1 Presynaptic Potential 0 2 Responses at Clamped Membrane Potentials o 3 Postsynaptic Responses of the Cells I Figure A o NMDA Receptor 0 This receptor is a bit more complicated it also has voltage sensitivity I So it is called Voltage Dependent Ligand Receptor 0 But unlike the ions that we studied before AMDA is not voltage sensitive because of Charged amino acids regions in the protein I It is instead due to an affinity spot for Magnesium which is drawn toward the gate by the potential of the cell I At resting potential the cell is negative enough to attract the Mg to bind 0 But after enough depolarization the Mg is kicked out and the channel is open assuming Glutamate is present 0 FigureB xx 3 i K L l39 l in g c ll l I l l 39 C l l39 I l I l l l U l rquotquottf lv39 H x U V l 39 l 4quot 39139 l l I u I l 1 l l 1 l l In ll 1 39Ji39 1 ll 1 Vaquot 1 ll 39 t Hquot I l039 399 l U l quot l quotWINquot ll quotx llM I x l quotx l39 o NMDA is mixed with AMPA and Kainate the synapse generally has both present 0 NMDA is also a Calcium Channel Vrev remains OmV o NMDA is a complex protein that also contains other modulatory sites I 1 Glycine CoAgonist o CoAgonist means that NMDA cannot actually function without Glycine being present 0 It needs both Glutamate and Glycine to bind in order to open up the channel 0 But Glycine is present in abundance Glial Cells excrete Glycine I 2 Zinc 2 Antagonist I 3 PCP Drug Antagonist 0 Typical Synapse 0 Has a mixed population of receptor types so we have to consider the effects of potential and charge on how the cell functions I 1 Resting Potential 0 An EPSP only has an effect on AMPA and Kainate receptors because NMDA are closed off due to Magnesium I 2 Action Potential 0 At such depolarization however Mg is kicked out o This means that Calcium can enter in rushes in 0 Calcium actually affects the Physical Properties of a Cell 0 One effect is the increased density of AMPA receptors 0 If more AMPA receptors are present then the EPSP response is larger and has a greater effect even under resting baseline potentials o This increased sensitivity and AMPA density relates to synaptic density 0 AMPA and NMDA Currents o How can we view the separated charges and currents that each induces I Recall doing so with Sodium and Potassium broke apart AP into components by clocking one discovering that Sodium is rapid and Potassium is slow I Similar technique here APV blocks NMDA Channels use of a selective Antagonist I We then View the Current NOT the Potential 0 Figure C 39 r l H V gijLJ H39 I quotX quotI LAquot t v I J I A 1 Q 39 Nquot 539 1quot li39 a 739 1311 39 39 6 39Ji 0939 1 I til 3939 f39 3 H quot439 H 39 4 I J 1 i I x I l x r I l quot R IllI 2 I Jquot J 39 39 I m a r I r 39V l39 Wig V xiii g l xii1 quot 39l 3 4 c I I 39 J l th39ztg 39ll g 39JL lf tquot H u in 39 1 v I 4 I 39 a 7quot itquot P4 4 39n39w39 i r MW a t 1 W E if I V I L h J iv A AI my AWN Wt L 0 1 r v Limi ML xle minim quotgm 2 gt quot 9 I i 39 l39 I l s I I 7 quotkl It I l 1 39L39 39a 4 Ui x law L 39 h A it 1 J l A I We see that when NMDA is blocked we only find an NMDA current after Mg has been kicked out a process that is seen at 40mV but very noticeable at ZOmV 8 Current voltage telattonshup at late component of the synaptic cunem Div 100 Late current romamwg atte39 blockade with APV l 1150 1 00 A 30 n bijV lv Late current NMDA A A q 00 A A l t zoo I lI A I A l I A Peak early current j nonNMDA 300 0 So we can then plot that data I When that is plotted we can compare the actual and theoretical NMDA currents 0 Would be linear but because of the probability associated with the Voltage and Magnesium block we find a curve until the Reversal change in which case Magnesium is completely gone and the curve is linear This linear curve matches the experimentally determined linear curve created by placing a neuron in a dish deprived of Magnesium It becomes the same as the Nicotinic curve
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