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Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
Neuroscience: Exploring the Brain, 3e
Chapter 5: Synaptic Transmission
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
Introduction
• Synaptic Transmission
– Information transfer at a synapse
– Plays role in all the operations of the nervous system
– 1897: Charles Sherrington- “synapse”
• Cajal vs Golgi (1906)
– Chemical and electrical synapses
• 1921- Otto Loewi
• 1959- Furshpan and Potter
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
Types of Synapses
• Direction of Information Flow
– In one direction: Neuron to target cell
– First neuron = Presynaptic neuron
– Target cell = Postsynaptic neuron
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
Type of Synapses
Golgi – Continuous
synapse
Cajal – Contiguous
synapse
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
– Gap junction
• Channel
• Connexon- formed by six connexins
– Cells are said to be “electrically coupled”
• Flow of ions from cytoplasm to cytoplasm
Electrical Synapse
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
INSERT FIG. 5.1 (Yes, deliberately out of order)
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
Electrical Synapse
– Very fast transmission
• Postsynaptic potentials (PSPs)
– Synaptic integration: Several PSPs occurring
simultaneously to excite a neuron (i.e. causes AP)
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
Chemical Synapse
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
Chemical
Synapse
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
• CNS Synapses (Examples)
– Axodendritic: Axon to dendrite
– Axosomatic: Axon to cell body
– Axoaxonic: Axon to axon
– Dendrodendritic: Dendrite to dendrite
Types of Synapses
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
• CNS Synapses (Examples)
– Gray’s Type I: Asymmetrical, excitatory
– Gray’s Type II: Symmetrical, inhibitory
Types of Synapses
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
• The Neuromuscular Junction
(NMJ)
– Studies of NMJ established
principles of synaptic
transmission
Types of Synapses
An Actual Neuromuscular Synapse
Goodsell, D. S. (2009), Neuromuscular synapse.
Biochem. Mol. Biol. Educ., 37: 204–210.
doi: 10.1002/bmb.20297
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
Principles of Chemical Synaptic
Transmission
• Basic Steps
– Neurotransmitter synthesis
– Load neurotransmitter into synaptic vesicles
– Depolarization  Vesicles fuse to presynaptic terminal
– Neurotransmitter spills into synaptic cleft
– Binds to postsynaptic receptors
– Biochemical/Electrical response elicited in postsynaptic cell
– Removal of neurotransmitter from synaptic cleft
Synaptic Transmission at Neuromuscular
Junction
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
Principles of Chemical Synaptic
Transmission
• Basic Steps
– Neurotransmitter synthesis
– Load neurotransmitter into synaptic vesicles
– Depolarization  Vesicles fuse to presynaptic terminal
– Neurotransmitter spills into synaptic cleft
– Binds to postsynaptic receptors
– Biochemical/Electrical response elicited in postsynaptic cell
– Removal of neurotransmitter from synaptic cleft
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
– Amino acids: Small organic molecules
Neurotransmitters
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
– Amino acids: Small organic molecules
– Amines: Small organic molecules
Neurotransmitters
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
– Amino acids: Small organic molecules
– Amines: Small organic molecules
– Peptides: Short amino acid chains (i.e. proteins)
stored in and released from secretory granules
Neurotransmitters
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
– ____ ____: Small organic molecules
• e.g., Glutamate, Glycine, GABA
– ____ : Small organic molecules
• e.g., Dopamine, Acetylcholine, Histamine
– ____ : Short amino acid chains (i.e. proteins) stored
in and released from secretory granules
• e.g., Dynorphin, Enkephalins
Neurotransmitters
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
Neurotransmitter Synthesis and Storage
Loading Neurotransmitters
Dense Core Vesicles
Goodsell, D. S. (2009), Neuromuscular synapse.
Biochem. Mol. Biol. Educ., 37: 204–210.
doi: 10.1002/bmb.20297
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
Exocytosis: Process by which vesicles release their contents
Neurotransmitter Release
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
• Process of exocytosis stimulated by release of
intracellular calcium, [Ca2+]i
• Proteins alter conformation - activated
• Vesicle membrane incorporated into presynaptic
membrane
• Neurotransmitter released
• Vesicle membrane recovered by endocytosis
Mechanism of Neurotransmitter release
(Clathrin-mediated endocytosis:
http://biochem.web.utah.edu/iwasa/projects/clathrin.html)
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
- Ionotropic: Transmitter-gated ion channels
Neurotransmitter Receptors and Post-
synaptic Response
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
– Metabotropic: G-protein-coupled receptor
Neurotransmitter Receptors and Post-
synaptic Response
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
• EPSP:Transient postsynaptic membrane depolarization by
presynaptic release of neurotransmitter
• IPSP: Transient hyperpolarization of postsynaptic membrane
potential caused by presynaptic release of neurotransmitter
• Reversal potential
Excitatory and Inhibitory Postsynaptic
Potentials
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
– Diffusion: Away from the synapse
– Reuptake: Neurotransmitter re-enters presynaptic
axon terminal
– Enzymatic destruction inside terminal cytosol or
synaptic cleft
– Desensitization: despite continued presence of ACh,
transmitter-gated channels close
Neurotransmitter Recovery and
Degradation
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
– Effect of drugs on nervous system tissue
– Receptor antagonists: Inhibitors of neurotransmitter
receptors
• Curare
– Receptor agonists: Mimic actions of naturally
occurring neurotransmitters
• Nicotine
– Defective neurotransmission: Root cause of
neurological and psychiatric disorders
Neuropharmacology
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
Principles of Synaptic Integration
– Process by which multiple synaptic potentials
combine within one postsynaptic neuron
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
– Synaptic vesicles: Elementary units of synaptic
transmission. Almost fixed amount of nerotransmitter
• Quantum: An indivisible unit
– Miniature postsynaptic potential (“mini”)
– Quantal analysis: Used to determine number of
vesicles that release during neurotransmission
– Neuromuscular junction: About 200 synaptic vesicles,
EPSP of 40mV or more
– CNS synapse: Single vesicle, EPSP of few tenths of a
millivolt
Quantal Analysis of EPSPs
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
– Allows for neurons to perform sophisticated
computations
– EPSP summation: EPSPs added together to produce
significant postsynaptic depolarization
– Spatial: EPSP generated simultaneously in different
spaces
– Temporal: EPSP generated at same synapse in rapid
succession
Synaptic Integration - EPSP Summation
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
Synaptic Integration - EPSP Summation
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
– Assume: Dendrite as a straight cable (~spinal motor
dendrite)
• Membrane depolarization falls off exponentially
with increasing distance
• Vx = Vo/ex/ 
• Dendritic length constant (): at which, 37% of Vo
– In reality, dendrites are very elaborate structures
that contribute to more complex integrative
properties
The Contribution of Dendritic Properties
to Synaptic Integration
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
Vx=Vo * e-x/λ
The Contribution of Dendritic Properties
to Synaptic Integration
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
– Dendrites of neurons: voltage-gated sodium,
calcium, and potassium channels
• Can act as amplifiers (vs. passive)
– Dendritic sodium channels: May carry electrical
signals in opposite direction, from soma outward
along dendrites (Cajal?)
Excitable Dendrites
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
– Action of synapses to take membrane potential away
from action potential threshold
– Exerts powerful control over neuron output
Inhibition
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
– Excitatory vs. inhibitory synapses: Bind different
neurotransmitters, allow different ions to pass through
channels
IPSPs and Shunting Inhibition
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
– Excitatory vs. inhibitory synapses: Bind different
neurotransmitters, allow different ions to pass through
channels
– Membrane potential more negative: hyperpolarizing IPSP
– ECl = -65 mV ?
• Shunting Inhibition: Inhibiting current flow from soma to
axon hillock
IPSPs and Shunting Inhibition
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
Shunting Inhibition
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
– Excitatory synapses
• Gray’s type I morphology
• Spines: Excitatory
synapses
– Inhibitory synapses
• Gray’s type II
morphology
• Clustered on soma and
near axon hillock
The Geometry of Excitatory and
Inhibitory Synapses
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
Concluding Remarks
• Chemical synaptic transmission
– Rich diversity allows for complex behavior
– Provides explanations for drug effects
– Defective transmission is the basis for many
neurological and psychiatric disorders
– Key to understanding the neural basis of learning
and memory
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
Question of the
Day
How stepping on a rusty nail may result in
muscle spasms and even eventual death?
Hint: It involves synaptic transmission.
- In general, what molecular/cellular events
happened? Are there effective treatments?
- Does the behavior a result of (mostly) defects in
inhibitory or excitatory synapse? How do these
defects affect synaptic integration?
Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
Principles of Synaptic Integration
• Modulation
– Synaptic transmission that
modifies effectiveness of
EPSPs generated by other
synapses with transmitter-
gated ion channels
– Example: Activating NE β
receptor

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Synthesis and Storage of Neurotransmitters

  • 1. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Neuroscience: Exploring the Brain, 3e Chapter 5: Synaptic Transmission
  • 2. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Introduction • Synaptic Transmission – Information transfer at a synapse – Plays role in all the operations of the nervous system – 1897: Charles Sherrington- “synapse” • Cajal vs Golgi (1906) – Chemical and electrical synapses • 1921- Otto Loewi • 1959- Furshpan and Potter
  • 3. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Types of Synapses • Direction of Information Flow – In one direction: Neuron to target cell – First neuron = Presynaptic neuron – Target cell = Postsynaptic neuron
  • 4. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
  • 5. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Type of Synapses Golgi – Continuous synapse Cajal – Contiguous synapse
  • 6.
  • 7. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins – Gap junction • Channel • Connexon- formed by six connexins – Cells are said to be “electrically coupled” • Flow of ions from cytoplasm to cytoplasm Electrical Synapse
  • 8. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins INSERT FIG. 5.1 (Yes, deliberately out of order)
  • 9. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Electrical Synapse – Very fast transmission • Postsynaptic potentials (PSPs) – Synaptic integration: Several PSPs occurring simultaneously to excite a neuron (i.e. causes AP)
  • 10. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Chemical Synapse
  • 11. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Chemical Synapse
  • 12. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins • CNS Synapses (Examples) – Axodendritic: Axon to dendrite – Axosomatic: Axon to cell body – Axoaxonic: Axon to axon – Dendrodendritic: Dendrite to dendrite Types of Synapses
  • 13. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
  • 14. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins • CNS Synapses (Examples) – Gray’s Type I: Asymmetrical, excitatory – Gray’s Type II: Symmetrical, inhibitory Types of Synapses
  • 15. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins • The Neuromuscular Junction (NMJ) – Studies of NMJ established principles of synaptic transmission Types of Synapses
  • 16. An Actual Neuromuscular Synapse Goodsell, D. S. (2009), Neuromuscular synapse. Biochem. Mol. Biol. Educ., 37: 204–210. doi: 10.1002/bmb.20297
  • 17. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Principles of Chemical Synaptic Transmission • Basic Steps – Neurotransmitter synthesis – Load neurotransmitter into synaptic vesicles – Depolarization  Vesicles fuse to presynaptic terminal – Neurotransmitter spills into synaptic cleft – Binds to postsynaptic receptors – Biochemical/Electrical response elicited in postsynaptic cell – Removal of neurotransmitter from synaptic cleft
  • 18. Synaptic Transmission at Neuromuscular Junction
  • 19. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Principles of Chemical Synaptic Transmission • Basic Steps – Neurotransmitter synthesis – Load neurotransmitter into synaptic vesicles – Depolarization  Vesicles fuse to presynaptic terminal – Neurotransmitter spills into synaptic cleft – Binds to postsynaptic receptors – Biochemical/Electrical response elicited in postsynaptic cell – Removal of neurotransmitter from synaptic cleft
  • 20. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins – Amino acids: Small organic molecules Neurotransmitters
  • 21. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins – Amino acids: Small organic molecules – Amines: Small organic molecules Neurotransmitters
  • 22. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins – Amino acids: Small organic molecules – Amines: Small organic molecules – Peptides: Short amino acid chains (i.e. proteins) stored in and released from secretory granules Neurotransmitters
  • 23. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins – ____ ____: Small organic molecules • e.g., Glutamate, Glycine, GABA – ____ : Small organic molecules • e.g., Dopamine, Acetylcholine, Histamine – ____ : Short amino acid chains (i.e. proteins) stored in and released from secretory granules • e.g., Dynorphin, Enkephalins Neurotransmitters
  • 24. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Neurotransmitter Synthesis and Storage Loading Neurotransmitters
  • 25. Dense Core Vesicles Goodsell, D. S. (2009), Neuromuscular synapse. Biochem. Mol. Biol. Educ., 37: 204–210. doi: 10.1002/bmb.20297
  • 26. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Exocytosis: Process by which vesicles release their contents Neurotransmitter Release
  • 27. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins • Process of exocytosis stimulated by release of intracellular calcium, [Ca2+]i • Proteins alter conformation - activated • Vesicle membrane incorporated into presynaptic membrane • Neurotransmitter released • Vesicle membrane recovered by endocytosis Mechanism of Neurotransmitter release (Clathrin-mediated endocytosis: http://biochem.web.utah.edu/iwasa/projects/clathrin.html)
  • 28. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins - Ionotropic: Transmitter-gated ion channels Neurotransmitter Receptors and Post- synaptic Response
  • 29. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins – Metabotropic: G-protein-coupled receptor Neurotransmitter Receptors and Post- synaptic Response
  • 30. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins • EPSP:Transient postsynaptic membrane depolarization by presynaptic release of neurotransmitter • IPSP: Transient hyperpolarization of postsynaptic membrane potential caused by presynaptic release of neurotransmitter • Reversal potential Excitatory and Inhibitory Postsynaptic Potentials
  • 31. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins – Diffusion: Away from the synapse – Reuptake: Neurotransmitter re-enters presynaptic axon terminal – Enzymatic destruction inside terminal cytosol or synaptic cleft – Desensitization: despite continued presence of ACh, transmitter-gated channels close Neurotransmitter Recovery and Degradation
  • 32. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins – Effect of drugs on nervous system tissue – Receptor antagonists: Inhibitors of neurotransmitter receptors • Curare – Receptor agonists: Mimic actions of naturally occurring neurotransmitters • Nicotine – Defective neurotransmission: Root cause of neurological and psychiatric disorders Neuropharmacology
  • 33. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Principles of Synaptic Integration – Process by which multiple synaptic potentials combine within one postsynaptic neuron
  • 34. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins – Synaptic vesicles: Elementary units of synaptic transmission. Almost fixed amount of nerotransmitter • Quantum: An indivisible unit – Miniature postsynaptic potential (“mini”) – Quantal analysis: Used to determine number of vesicles that release during neurotransmission – Neuromuscular junction: About 200 synaptic vesicles, EPSP of 40mV or more – CNS synapse: Single vesicle, EPSP of few tenths of a millivolt Quantal Analysis of EPSPs
  • 35. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins – Allows for neurons to perform sophisticated computations – EPSP summation: EPSPs added together to produce significant postsynaptic depolarization – Spatial: EPSP generated simultaneously in different spaces – Temporal: EPSP generated at same synapse in rapid succession Synaptic Integration - EPSP Summation
  • 36. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Synaptic Integration - EPSP Summation
  • 37. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins – Assume: Dendrite as a straight cable (~spinal motor dendrite) • Membrane depolarization falls off exponentially with increasing distance • Vx = Vo/ex/  • Dendritic length constant (): at which, 37% of Vo – In reality, dendrites are very elaborate structures that contribute to more complex integrative properties The Contribution of Dendritic Properties to Synaptic Integration
  • 38. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Vx=Vo * e-x/λ The Contribution of Dendritic Properties to Synaptic Integration
  • 39. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins – Dendrites of neurons: voltage-gated sodium, calcium, and potassium channels • Can act as amplifiers (vs. passive) – Dendritic sodium channels: May carry electrical signals in opposite direction, from soma outward along dendrites (Cajal?) Excitable Dendrites
  • 40. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins – Action of synapses to take membrane potential away from action potential threshold – Exerts powerful control over neuron output Inhibition
  • 41. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins – Excitatory vs. inhibitory synapses: Bind different neurotransmitters, allow different ions to pass through channels IPSPs and Shunting Inhibition
  • 42. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins – Excitatory vs. inhibitory synapses: Bind different neurotransmitters, allow different ions to pass through channels – Membrane potential more negative: hyperpolarizing IPSP – ECl = -65 mV ? • Shunting Inhibition: Inhibiting current flow from soma to axon hillock IPSPs and Shunting Inhibition
  • 43. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Shunting Inhibition
  • 44. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins – Excitatory synapses • Gray’s type I morphology • Spines: Excitatory synapses – Inhibitory synapses • Gray’s type II morphology • Clustered on soma and near axon hillock The Geometry of Excitatory and Inhibitory Synapses
  • 45. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Concluding Remarks • Chemical synaptic transmission – Rich diversity allows for complex behavior – Provides explanations for drug effects – Defective transmission is the basis for many neurological and psychiatric disorders – Key to understanding the neural basis of learning and memory
  • 46. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Question of the Day How stepping on a rusty nail may result in muscle spasms and even eventual death? Hint: It involves synaptic transmission. - In general, what molecular/cellular events happened? Are there effective treatments? - Does the behavior a result of (mostly) defects in inhibitory or excitatory synapse? How do these defects affect synaptic integration?
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  • 48. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Principles of Synaptic Integration • Modulation – Synaptic transmission that modifies effectiveness of EPSPs generated by other synapses with transmitter- gated ion channels – Example: Activating NE β receptor