MOLECULAR NEUROBIOLOGY MCDB 4777
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This 26 page Class Notes was uploaded by Mrs. Willis Mante on Thursday October 29, 2015. The Class Notes belongs to MCDB 4777 at University of Colorado at Boulder taught by Staff in Fall. Since its upload, it has received 10 views. For similar materials see /class/231842/mcdb-4777-university-of-colorado-at-boulder in Molecular, Cellular And Developmental Biology at University of Colorado at Boulder.
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Date Created: 10/29/15
MCDB 47775777 Molecular Neurobiology Lecture 10 Synapse mechanisms calcium vesicle cycle and postsynaptic permeability changes Topics for today Experimental evidence for vesicle fusion and reuptake Experimental evidence for calcium role in transmitter release Molecules of the core complex regulating release Rusty nails and wrinkles Neurotransmitters in action 51 Electrical and chemical synapses differ fundamentally in their transmission mechanisms A ELECTRONIC SYNAPSE B CHEMICAL SYNAPSE Microtubule Presynaptic neuron Postsynap c neuron Gap junction NEUROSCIENCE Third Edition Figure 51 o 2004 Smalls Associaies in 57 Quantized distribution of EPP amplitudes evoked in a low Ca2 solution Bernard Katz s expts Number of EPPs 20 1 2 16 20 EPP amplitude mV r Pam 57 Quantized distribution of EPP amplitudes evoked in a low Ca2 solution Part 2 13 Number of MEPPs J O p O O llllll llll illl IIIN III III LII iwil wgii I39ll II III II IWII II III III lli II Illw Il El ij i I I t 0 04 08 MEPP amplitude mV K num n 1 pm 2 tress 3 gamma my 4AP concentration 10 3M 39 3000 2000 Number of vesicles fusing 1000 O 0 1000 2000 3000 4000 5000 6000 Number of quanta released r m am n m Vesicle fusing with plasma membrane NEUROSCIENCE Fourth Edition Figure 58 Part 1 Dzuussmauemssccmawnc 58 Relationship of synaptic vesicle exocytosis and quantal transmitter release Part 2 C F nn s A Dan 59 Local recycling of synaptic vesicles in presynapticterminals Part 1 A B Wash away Brie extracellular HRP stimuilate wait 5 minutes gt gt presynap c terminal Horseradish peroxidase C 1 hour later r Inm nl n1 59 Local recycling of synaptic vesicles in presynaptic terminals Part 2 E Endocytosis Budding 39 39 2 J O Q xi Budding Docking Fusion Exocytosis 510 Entry of Ca2 through voltagedependent calcium channels causes transmitter release Part 1 A Presynap dc neuron Voltage clamping a squid synapse V th TTX and K Postsynaptic Channel block 1 neuron pre B 0 CONTROL CADMIUM ADDED Presynaptic membrane potential 111V cam P Msunmtsm wmm am Presynap c current lIA cmz Fostsynaptic potential mV 12 e3 0 Time ms mmmmmmmmnwm mum m 511 Evidence that a rise in presynaptic Ca2 concentration triggers transmitter release Part 1 A l l 250um Presynaptic Ca injection Ca is sufficient for neurotransmitter release E Q g 5 A E 2 Imaging Ca Influx after 5 action potentials with a 3 5g fluorescent dye 3 g a 6 O m Time s 511 Evidence that a rise in presynaptic Ca2 concentration triggers transmitter release Part 2 C 25 CONTROL INJECT Ca2BUFFER 9 E 9 0 E 5 S TU 25 a g 50 i a 93 75 at 0 EA 25 Presynaptic Ca buffer a E injection Ca is necessary 35 0 for neurotransmitter release 35 39E 25 3 50 59 A 8 L 75 0 1 2 3 4 5 0 1 2 3 4 5 Time ms 512 Differential release of neuropeptide and smallmolecule cotransmitters Small molecule neuro transmitter in small clear core vesicles Neuropeptide in large dense core vesicles Localized increase in Ca2 concentration LJL Lowfrequency stimulation More diffuse increase in Ca2 Q a On Highfrequency stimulation NEUROSCIENCE Third Edition Figure 512 o 2004 summer Assumes In 514 Molecular mechanisms of neurotransmitter release Part 3 Hsc 7O Auxilin Synaptojanin Endosome Dynamin Clathrin Ca2 Synaptotagmin NSF SNAPS SN ARES Figure 513 Presynaptic proteins and their roles in synaptic vesicle cycling Part 1 A SNAPZS Synaptobrevin Vt39ila r Synaptotagmin V ATPase wr I r 1C3 Synaptophysin SNAP29 CSP 8V2 VAMP4 SCAMP Syntaxin v 39 Synaps39m VGLUT munc18 Rab3A Trimeric Other GTPase transporter NEUROSCIENCE Fourth Edition Figure 513 Part 1 2005SinauerAssucMesnnu 3 11mm you mama Clamrln Am Syndlpm WASP NSF 5m synmphilln SNU39 Figure 514 Molecular mechanisms of exocytosis during neurotransmitter release Part 1 Synaptobrevili My M 4 mMui v w A 3 1 that gawk F i Presynaptic plasma membrane NEUROSCIENCE Fourth Edition Figure 514 Part 1 Dzuussinauer Assocmasinc Figure 514 Molecular mechanisms of exocytosis during neurotransmitter release Part 2 i 1 Vesicle docks Synaptobrevin Vesicle K g Ca2 channel I I Syntaxin 5N A1125 2 SNARE complexes form to pull membranes together Regulated by NSF NEM sensitive fusion protein and SNAPs soluble NSF attatchment proteins also involved in ERGolgi membrane fusions SNARE SNAP receptors Figure 514 Molecular mechanisms of exocytosis during neurotransmitter release Part 3 3 Entering Ca2 binds to synaptotagmin 4 CaZbound synaptotagmin catalyzes membrane fusion 2005 sinauer Associates inn Box 50 Toxins That Affect Transmitter Release 1 Synaptobrevin mg gs 9 P91 3 quotT 3 39 m mwa M r quotfgw a 39 9 V ttttt T Wt I tattttwttttt Syntaxin Presynap c plasma membrane NEUROSCIENCE Fourth Edition Box 50 e sssssssssssssssssssssss c Figure 515 Molecular mechanisms of endocytosis following neurotransmitter release A Clathrin triskelion NEUROSCIENCE Fourth Edition Figure 515 2006 Slnauar Associates inc 515 Activation ofACh receptors at neuromuscular synapses Part 1 membrane patch ACh receptor 515 Activation ofACh receptors at neuromuscular synapses Part 2 B Currents produced by 1 SINGLE OPEN CHANNEL lt ACh release by stimulating motor neuron Number 0 q w 0 of open 1 H 2 Channels zr ii WWWWWW h 74 E 2 FEW OPEN CHANNELS 5 1 Q Q Number 0 0 B of open 39 H channels 10 20 g 3 ALL7CHANNELS OPEN Es 0 1 0 Number of Open 200000 Channels 300000 600000 4024 6 8101214 Timems
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