Neurobiology Lectures:   Cell to Cell Chatter 3. The Synapse

THE SYNAPSE: COMMUNICATION BETWEEN NEURONS - INDEX

Synapse 1:  Gap Junctions and Chemical Synapses; MEPPs, Fatt and Katz, Quantal Release
Synapse 2:  Pre-synaptic Events - Quantal Release, Neurotransmitters - Vesicle Release
Synapse 3:  Post-synaptic Events - Ligand Gated Ion Channels, G-protein Coupled Receptors, 2nd Messenger Networks
Synapse 4:  Synaptic Inactivation, Dendritic Integration.
Synapse Papers

• Third Essay Assignment (due Week 8):  The Synapse: Structural, Ionic and Molecular Propterties; Diversity, Dynamics and Integration.

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Full Set of Synapse References

Synapse 1: Neural Connections: Gap Junctions and Chemical Synapses. Neuromuscular Junction (NMJ) of the frog and Miniature End Plate Potentials (MEPPs). Quantal Release Theory (Neurotransmitter). (Fatt, Katz, Kuffler, Eccles, del Castillo)

• Topic Outline (Synapse1)
• Lecture Notes (S1)
  
• Synapse Slides #1 (Powerpoint)

• PAPER: Adrian & Lucas (1912) Prototype physiological study of frog muscle.
• PAPER: Eccles, Katz & Kuffler (1941) Characterization of End Plate Potentials (EPPs) in frog muscle - relationship between EPP and Action Potential (AP), summation of EPPs (equivalent to summation of synapses / ion currents in neuronal dendrites).
• Fatt & Katz (1951) Intracellular studies of EPPs - decay with distance from synapse; use of curare to block ACh receptors - allowing visualization of EPPs without AP.
• PAPER: Fatt P & B Katz (1952) Miniature End Plate Potentials (MEPPs) - fundamental units of synaptic activation.
• PAPER: del Castillo J & B Katz (1954b) Histogram analysis of MEPP sumation - suggesting MEPPs are activated by "quanta" of neurotransmitter (note: neurotransmitter vesicles had not yet been observed).

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Full Set of Synapse References

Synapse 2: Pre-synaptic Events: More Quantal Release; Neurotransmitters (ACh, catacholamines, amino acids, peptides); Neurotransmitter synthesis, storage and release. Neurotransmitter vesicles.

• Topic Outline (Synapse2)
• Lecture Notes (S2a), Part 1
  
• Lecture Notes (S2b), Part 2
  
• Synapse Slides #2 (Powerpoint)

• Excellent course web site with focus on release of synaptic vesicles

• PAPER: del Castillo & Katz (1954a) Ca++ stimulates ACh release; Mg++ blocks it - study of use of Mg++ to reduce MEPPs.
• PAPER: del Castillo J & B Katz (1954b) Histogram analysis of MEPP sumation - suggesting MEPPs are activated by "quanta" of neurotransmitter (note: neurotransmitter vesicles had not yet been observed).
• PAPER: Robertson (1956) First electronmicrograph showing synaptic vesicles (quanta?)
• PAPER: Hartzell, Kuffler & Yoshikami (1975) How much ACh is in a Quanta? Quantification!
• PAPER: Hurlbut, Iezzi, Fesce & Ceccarelli (1990) Correlation between quantal secretion and vesicle loss at the frog neuromuscular junction.
• PAPER: Stevens (1993) Quantal release and Long-Term Potentiation. (review)
• PAPER: Kelly (1993) Storage and release of neurotransmitters. (review)
• PAPER: Whittaker, Michaelson & Kirkland (1964) Synaptosomes: the tissue preparation that opened the door on synaptic biochemistry.
• PAPER: Albright, Jessell, Kandel & Posner (2000) Neural Science @ 2000. See Figure 7 re. synaptic vesicle biochemistry.
• PAPER: Yoshihara et al. (2003) The roles of Ca++ and synaptotagmin in vesicle release.
• PAPER: Han and Jackson (2006) Recent paper describing Ca++ and fusion pore proteins in vesicle release.

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Full Set of Synapse References

Synapse 3: Post-synaptic Events: Receptors, Second Messengers and Ion Channels. Ligand Gated Ion Channels and G-protein Coupled Receptors.

• Topic Outline (Synapse3)
• Lecture Notes (S3)
  
• Synapse Slides #3 (Powerpoint)
  
• G-Protein Transduction Pathways (drawings) (Adobe PDF)

• PAPER: Unwin (1993) Structure of Nicotinic ACh receptor (ligand gated ion channel). (review)
• PAPER: Vogt (2006) "How sensitive is a nose?" Sci. STKE 2006, pe8. [Comments on the common transduction mechanisms in vision and olfaction.]

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Full Set of Synapse References

Synapse 4: Turning Off the Synapse (including Neurotransmitter inactivation). Synaptic Integration: competition of synaptic biochemical pathways; summation of dendritic currents.

• Topic Outline (Synapse4)
• Lecture Notes (S4)
  
• Synapse Slides #4 (Powerpoint)
  
• Ionic Currents in Dendrites and Axons: Summation of Dendritic Currents and Propagation of Action Potentials

• PAPER: Gonzalez & Robinson (2004) Neurotransmitter Inactivation: Neurotransmitter Transporters.

• PAPER: Segev (1992) Modeling ion currents in dendrites and action potentials in axons.
  
• PAPER: Eilers & Konnerth (1997) Dendritic signal integration.
  
• PAPER: Hausser & Mell (2003) Integrative Compartments within Dendrites
  
• PAPER: Bourne & Nicoll (1993) Parallel post-synaptic transductory pathways integrate multiple NT signals.
  
• PAPER: Stuart etal, 1997, Action potentials in dendrites - modulating integration.
  
• PAPER: vanWelie & Spier, 2002, Initation of Action Potentials in Axons.
  
• PAPER: Williams & Stuart (2002) Influence of individual synapses on the generation of Action Potentials.
  

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G-Protein Web Links
     Cartoon movies showing GPCRs in action.
     G-protein structure ? Requires free Chime plugin to view structures.
     Another Structure of G-proteins - Requires free Chime plugin to view structures.
     Interaction with G-proteins and Adenylate Cyclase (PDF).
     Interactions between G-protein / Adenylate Cyclase / Protein Kinase (PDF)

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Synapse References

Synapse I

• PDF Adrian ED & K Lucas (1912) On the summation of propagation disturbances in nerve and muscle. Journal of Physiology 44, 68-124.

• PDF Katz B, Kuffler SW (1941) Multiple motor innervation of the frog's sartorius muscle. Journal of Neurophysiology 4, 207-223.

• PDF Eccles JC, B Katz & SW Kuffler (1941) Nature of the "endplate potential" in curarized muscle. Journal of Neurophysiology 4, 362-387.

• PDF Fatt P & B Katz (1951) An analysis of the end-plate potential recorded with an intra-cellular electrode. Journal of Physiology 115, 320-370.

• PDF Fatt P & B Katz (1952) Spontaneous subthreshold activity at motor nerve endings. Journal of Physiology 117, 109-128.

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Quantal release theory.

• PDF del Castillo J, Stark L (1952) The effect of calcium ions on the motor end-plate potentials. Journal of Physiology 116, 507-515.

• PDF del Castillo J & B Katz (1954a) The effect of magnesium on the activity of motor nerve endings. Journal of Physiology 124, 553-559.

• PDF del Castillo J & B Katz (1954b) Quantal components of the end-plate potential. Journal of Physiology 124, 560-573.

• PDF del Castillo J & B Katz (1954c) Statistical factors involved in neuromuscular facilitation and depression. Journal of Physiology 124, 574-585.

• PDF del Castillo J & B Katz (1954d) Changes in end-plate activity produced by pre-synaptic polarization. Journal of Physiology 124, 586-604.

• PDF Robertson JD (1956)The ultrastructure of a reptilian myoneural junction. Journal of Biophysical and Biochemical Cytology 2, 381-394. [The first Electronmicrographs of synaptic vesicles]

• PDF Hartzell HC, SW Kuffler & D Yoshikami (1975) Post-synaptic potentiation: interaction between quanta of acteylcholine at the skeletal neuromuscular synapse. Journal of Physiology 251, 427-463.

• PDF Kuffler SW & D Yoshikami (1975) The number of transmitter molecules in a quantum: an estimate from iontophoretic application of acetylcholine at the neuromuscular synapse. Journal of Physiology 251, 465-482.

• PDF Hurlbut WP, Iezzi N, Fesce R, Ceccarelli B 1990) Correlation between quantal secretion and vesicle loss at the frog neuromuscular junction. Journal of Physiology 425, 501-526.

• PDF Stevens CF (1993) Quantal release of neurotransmitter and Long-Term Potentiation. Cell 72 / Neuron 10 (suppl.), 55-63.

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Synaptosomes and Synapsin: Birth of Pre-Synaptic Biochemistry

• PDF Whittaker VP, Michaelson IA, Kirkland RJA (1964) The separation of synaptic vesicles from nerve-ending particles ('Synaptosomes'). Biochemical Journal 90, 293-303.

• PDF Ueda T, Greengard P (1977) Regulation of endogenous phosphorylation of specific proteins in synaptic membrane fractions from rat brain by adenosine 3':5'-monophosphate. Journal of Biological Chemistry 248, 8295-8305.

• PDF Ueda T, Greengard P (1977) Adenosine 3':5'-monophosphate-regulated phosphoprotein system of neuronal membranes. I. Solubilization, purification, and some properties of endogenous phosphoprotein. Journal of Biological Chemistry 252, 5155-5163.

• PDF de Camilli P, Ueda T, Bloom FE, Battenberg E, Greengard P (1979) Widespread distribution of Protein I in the central and peripheral nervous systems. Proceedings of the National Academy of Sciences USA 11, 5977-5981.

• PDF Bloom FE, Ueda T, Battenberg E, Greengard P (1979) Immunocytochemical localization, in synapses, of Protein I, an endogenous substrate for protein kinases in mammalian brain. Proceedings of the National Academy of Sciences USA 11, 5982-5986.

• PDF de Camilli P, Cameron R, Greengard P (1983) Synapsin I (Protein I), a neve terminal-specific phosphoprotein. I. Its general distribution in synapses of the central and peripheral nervous system demonstrated by immunofluorescence in frozen and plastic sections. Journal of Cell Biology 96, 1337-1354.

• PDF de Camilli P, Harris Jr. SM, Huttner WB, Greengard P (1983) Synapsin I (Protein I), a neve terminal-specific phosphoprotein. II. Its specific association with synaptic vesicles demonstrated by immunocytochemistry in agarose-embedded synatpsomes. Journal of Cell Biology 96, 1355-1373.

• PDF Huttner WB, Schiebler W, Greengard P, de Camilli P (1983) Synapsin I (Protein I), a neve terminal-specific phosphoprotein. III. Its association with synaptic vesicles studied in a highly purified synaptic vesicle preparation. Journal of Cell Biology 96, 1374-1388.

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Special and joint issue of Cell (v.72) and Neuron (v. 10), 1993, reviewing contemporary issues relating to synapses and circuits:

• PDF Jessell TM & ER Kandel (1993) Synaptic transmission: a bidirectional and self-modifiable form of cell-cell communication. Cell 72 / Neuron 10, (suppl.), 1-30.

• PDF Unwin N (1993) Neurotransmitter action: opening of ligand-gated ion channels. Cell 72 / Neuron 10 (suppl.), 31-42.

• PDF Kelly RB (1993) Storage and release of neurotransmitters. Cell 72 / Neuron 10, (suppl.), 43-54.

• PDF Bourne HR, Nicoll R (1993) Molecular machines integrate coincident synaptic signals. Cell 72 / Neuron 10, (suppl.), 65-75.

• PDF Hall ZM & JR Sanes (1993) Synaptic structure and development: the neuromuscular junction. Cell 72 / Neuron 10, (suppl.), 99-122.

• PDF Stevens CF (1993) Quantal release of neurotransmitter and Long-Term Potentiation. Cell 72 / Neuron 10, (suppl.), 55-63.

• PDF Goodman CS, Shatz CJ (1993) Developmental mechanisms that generate precise patterns of neuronal connectivity. Cell 72 / Neuron 10, (suppl.), 77-98.

• PDF DeVries SH, Baylor DA (1993) Synaptic circuitry of the retina and olfactory bulb. Cell 72 / Neuron 10, (suppl.), 139-149.

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Special and joint issue ofCell (v. 100) and Neuron (v. 25, 2000, reviewing contemporary issues:

• PDF Albright TD, Jessell TM, Kandel ER, Posner MI (2000) Neural Science: a century of progress and the mysteries that remain. Cell 100 / Neuron 25, S1-S55.

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Circuits and Synaptic Configurations.


• PDF DeVries SH, Baylor DA (1993) Synaptic circuitry of the retina and olfactory bulb. Cell 72 / Neuron 10, (suppl.), 139-149.

• PDF Getchell TV, Shepherd GM (1975a) Synaptic actions on mitral and tufted cells elicited by olfactory nerve volleys in the rabbit. Journal of Physiology 251, 497-522. (front page and figure only)

• PDF Getchell TV, Shepherd GM (1975b) Short-axon cells in the olfactory bulb: dendrodentritic synaptic interactions. Journal of Physiology 251, 523-548. (front page and figure only)

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Developmental Mechanisms, axonal guidance to synaptic targets & synaptogenesis


• PDF Goodman CS, Shatz CJ (1993) Developmental mechanisms that generate precise patterns of neuronal connectivity. Cell 72 / Neuron 10, (suppl.), 77-98.

• PDF Chiba A, Rose D (1998) "Painting" the target: how local molecular cues define synaptic relationships. BioEssays 20, 941-948.

• PDF Keshishian H, Chiba A (1993) Neuromuscular development in Drosophila: insights from single neurons and single genes. Trends in Neuroscience 16, 278-283.

• PDF Hall ZM & JR Sanes (1993) Synaptic structure and development: the neuromuscular junction. Cell 72 / Neuron 10, (suppl.), 99-122.