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L32 2009 Synapses

L32 2009 Synapses - SYNAPSES Nov 11 2009 Scanning EM of...

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Unformatted text preview: SYNAPSES Nov. 11, 2009 # Scanning EM of synaptic terminals on the cell body of a neuron in the sea slug Aplysia illustrate the density of cell-cell contacts within the nervous system Lecture 32 !" $ ( 6 ,- . /0 & $ $ - 3 $# & '( ) * + $ ! $%# %1 $& ! 23 $ 4 5 3$ 5# , FIGHT HUNGER! . Shoals Marine Laboratory OPEN HOUSE Shoals ! " #$ % &' && (') *+ November 11: Tatkon Center, 5 – 7 pm 4 summer courses and internships 4 financial aid available www.sml.cornell.edu Webquiz question cut-off Here is the full question: “The process of countercurrent exchange appears frequently in biology. Consider the flow of blood to a ducks feet in the winter. The temperature of the arterial blood as it enters the leg from the body is 40 oC and when it enters the foot, the temperature has been reduced to 5 oC. Assuming efficient exchange of heat between the arterial and venous blood in the leg, which answer most closely approaches the maximum possible temperature of the venous blood leaving the foot ___ oC and the maximum possible temperature of the venous blood returning to the body from the leg is __ oC. HINT: It is strongly recommended that you draw yourself a picture to answer this question.) " Neuronal concepts & terms action potential activation gate all-or-none astrocyte axon axon hillock axon initial segment axon terminal dendrite depolarization equilibrium potential falling phase glia hyperpolarization inactivation gate membrane potential soma myelin sheath spike Nernst equation threshold neuroglia undershoot oligodendrocyte voltage-gated channels overshoot polarization potassium current propagation resting potential rising phase Schwann cell sodium current sodium-potassium ATPase This was also posted on the announcements website: http://courses.cit.cornell.edu/biog1101/announcements.htm Where we’re going today 1. voltage-gated channels 2. synapse types 3. neurotransmitters 4. receptor types 5. synaptic integration The ionic basis of action potential was worked out in the giant axon of the squid How do we know about channels? TOXINS! Na+ channels Tetrodotoxin (TTX) (from Japanese Puffer Fish, or FUGU) selective blocker of Na+ channels. Alan Hodgkin Andrew Huxley Nobel Prize 1963 K+ channels Axon diameter 0.5 mm Ionic composition determined by squeezing out contents (high K+, low Na+) Inserted wire electrode records voltage TEA (Tetraethyl ammonium ion) blocks K+ channels selectively TTX Voltage gated channels in myelinated axons are found only at the Nodes of Ranvier. Teased sciatic nerve to reveal individual neurons Green: Na+ channels Blue: K+ channels Red: Caspr (a protein marker of the paranodal region) Fugu Sashimi MS is an autoimmune attack on myelin Myelinated Neurons –saltatory conduction Current jumps from one node to the next. The velocity can reach 150 m/s. Na+ Voltage-gated Potassium Channel Single subunit K+ cell body + + Na+ K+ + Active channel is composed of 4 subunits that can vary depending upon the tissue Variation provides different dynamics and binding properties Voltage-gated sodium channel Voltage-gated sodium channel 4 subunits in the channel keeps channel open longer DDT Very large protein. No structure yet, but 4 repeat domains, each with 6 TM domains. S4 region acts as voltage sensor (+ charged positive). Region between S5 and S6 is selectivity filter. Voltage-gated calcium channel Patch recordings confirm channel existence Fine glass microelectrode, polished tip, isolates patch of membrane Tight seal (suction) Trans-membrane currents: transient opening and closing of channels E. Neher B. Sakmann Nobel Prize 1991 current (pA) Synapses A. Electrical fast excitatory “gap junction” connexon Synapses B. Chemical slower excitatory inhibitory post-synaptic cell synaptic cleft vesicles of transmitter pre-synaptic cell axon terminal Chemical synapses 0 Action potential invades the axon terminal 5 Axon terminal Synaptic vesicles containing neurotransmitter K+ Na+ (tyrosine) Presynaptic membrane (tyrosine) Voltage-gated Ca2+ channel 1 Ca2+ 2 3 4 (tryptophan) Postsynaptic membrane 6 Synaptic cleft Ligand-gated ion channels 7 Neurotransmitter is degraded by enzymes in the cleft recycled into the pre-synaptic terminal by pinocytosis First transmitter discovered in 1926 “Vagusstoff” = Acetylcholine (ACh) LOEWI’s EXPERIMENT Stimulator Two types of acetylcholine receptors on muscle: Nicotinic & Muscarinic Nicotinic Otto Loewi, Nobel Prize 1936 Muscarinic Muscarine (Amanita muscaria) Agonist Antagonist Nicotine (Nicotiana tabacum) Vagus nerve Curare (Strychnos toxifera) Atropine (Atropa belladonna) Frog Heart donor stimulus on Receptor type ionotropic recipient Acetylcholine inhibits contraction of heart muscle metabotropic Agonist: a drug or compound that mimics the effect of the neurotransmitter Antagonist: a drug which blocks the neurotransmitter or the agonist. Original Sources for Nicotine, Muscarine, Curare, Atropine Nicotiana tabacum Solanaceae ACh receptor types nicotinic muscarinic Amanita muscaria Strychnos toxifera Loganiaceae Atropa belladonna Solanaceae GABA and the GABA Receptor - amino butyric acid GABA and the GABA Receptor Agonists: Antagonists: Diazepine (i.e. Valium) Picrotoxin, Bicuculline (relaxant) (convulsant) Where found: • Central nervous system (diverse pathways) e.g., Purkinje cells of cerebellum • Crayfish stretch receptor Physiology: • ligand-gated ion channel • sudden increase in Chloride ion permeability • hyperpolarization of post synaptic membrane (IPSP). • rapid (delay = c. 1 ms). Single subunit Clicker question During an action potential when voltage-gated sodium channels initially open, sodium ions … A. flow down their concentration gradient by passive diffusion B. move down their electrical gradient C. move against their electrical gradient by active transport D. flow down their concentration gradient and down their electrical gradient E. flow down their concentration gradient and against their electrical gradient ++ +++ -65 mV -70 mV 0 2 4 6 8 10 12 14 ms Excitatory synapse Inward positive current depolarizes post-synaptic cell in a graded manner (typically Na+) (not all-or-none) excitatory post synaptic potential EPSP Inhibitory synapse Inward negative or positive outward current hyperpolarizes post-synaptic cell (typically Cl-) (typically K+) (in a graded manner) Q: Why are there so many synaptic contacts? A: Synaptic integration. inhibitory post synaptic potential IPSP 8 _____ -70 mV 0 -75 mV 2 4 6 10 12 14 ms Scanning EM of axon terminals contacting a neuron in the sea slug Aplysia. Integration and decision making at chemical synapses Integration and decision making at chemical synapses membrane voltage (mV) threshold membrane voltage (mV) threshold time time Two EPSPs separated in time (no spike) Two EPSPs close in time (=> spike). TEMPORAL SUMMATION Two EPSPs from different synapses (=> spike) SPATIAL SUMMATION EPSP + IPSP (=> no spike) INHIBITION Two EPSPs separated in time (no spike) Two EPSPs close in time (=> spike). TEMPORAL SUMMATION Two EPSPs from different synapses (=> spike) SPATIAL SUMMATION EPSP + IPSP (=> no spike) INHIBITION Up next Sensory systems ...
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