1. Chapter 8 Synaptic Transmission and Neural Integration
Electrical synapses 電性突觸
Chemical synapses 化學性突觸
Neural integration 神經整合
Presynaptic modulation 突觸前調節
Neurotransmitters: structure, synthesis, and degradation 神經傳導物質: 結構、合成及分解

2. I. Electrical Synapses
Synapses  anatomically specialized junction between two neurons or neuron and effector organ  electrical and chemical synapses
Electrical synapse  two neurons linked together by gap junctions
Function in nervous system  rapid communication; bidirectional communication; excitation/inhibition at same synapse
Some between neurons and glial cells
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3. II. Chemical Synapse Synapse
Presynaptic Cell
Postsynaptic Cell NT R
Synapse
The vast majority of synapses in the nervous system are chemical synapses  one neuron (presynaptic cell 突觸前細胞) secretes a neurotransmitter (NT) into the extracellular fluid  the neurotransmitter then binds to receptor (R) on the plasma membrane of a second cell (postsynaptic cell 突觸後細胞)
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4. Functional Anatomy of Chemical Synapses
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Synapse can occur at dendrites (axodendritic synapses), at the cell body (axosomatic synapses), or with another axon (axoaxonic synapses)
Most often the presynaptic neuron’s axon terminal forms a synapse with either a dendrite or the cell body of the postsynaptic neuron
In some cases the presynaptic neuron’s axon terminal forms a synapse with the postsynaptic neuron’s axon terminal
Signaling across a synapse is unidirectional--the presynaptic neuron communicates to the postsynaptic neuron
Figure 8.1 Neuron-neuron chemical synapses. P

5. Functional Anatomy of Chemical Synapses
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The presynaptic neuron at rest  calcium channels are closed, and no neurotransmitter is being releasing
In all cases, the axon terminal of the presynaptic neuron releases neurotransmitters into the narrow (30-50 nm) space between the two cells, called the synaptic cleft
Figure 8.2 Functional anatomy of a synapses. P

6. Functional Anatomy of Chemical Synapses
The membrane is depolarized by the arrival of action potential ()  Ca2+ channels open ()  Ca2+ enters the cell and triggers the release of neurotransmitter (NT) by exocytosis ()
NT diffuses across the synaptic cleft & some of it binds to receptors on the presynaptic cell membrane ()  a response is produced in the postsynaptic cell ()
Response terminated by NT removing from receptor & some NT is degraded by enzyme (); some NT is take up by the presynaptic cell (); some NT diffuses away from the synaptic cleft ()
Figure 8.2 Functional anatomy of a synapses.
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7. Synaptic Delay
Most neurotransmitters are synthesized in the cytosol of the axon terminal & are actively transported into synaptic vesicles, where they are stored until their eventual release by exocytosis
Most abundant in the membrane of the axon terminal are voltage-gated calcium channels  these channels open when the axon terminal is depolarized
It takes approximately 0.5~5 msec from the time an action potential arrives at the axon terminal before a response occurs in the postsynaptic cell  called the synaptic delay
This time lag is mostly due to the time required for calcium to trigger the exocytosis of neurotransmitter
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8. Signal Transduction Mechanisms at Chemical Synapses--Fast Response
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When the neurotransmitter (NT) binds to receptor  it can induce in a postsynaptic neuron either a fast or a slow response
The fast response occurs whenever a NT binds to a channel-linked receptor, also called an ionotropic receptor
Figure 8.3 Signal transduction mechanisms at chemical synapses.
The binding of the NT opens the ion channel  allow a specific ion to permeate the plasma membrane  change the electrical properties of the postsynaptic neuron
The typical response is a change in the membrane potential, called a postsynaptic potential (PSP)  which occurs very rapidly and turns off rapidly P

9. Signal Transduction Mechanisms at Chemical Synapses--Slow Response
Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings.
Slow responses are mediated through G protein-linked receptors called metabotropic receptors
The G protein can serve as a direct coupling between the receptor and the ion channel
G proteins can trigger either the opening or the closing of ion channels  alters a specific ion to permeate the plasma membrane  change the electrical properties of the postsynaptic neuron
Figure 8.3 Signal transduction mechanisms at chemical synapses.
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10. Signal Transduction Mechanisms at Chemical Synapses--Slow Response
Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings.
When the G protein functions as part of a second messenger system, it either activates or inhibits an enzyme that produces the second messengers, which then either opens or closes an ion channel or produces some other response in the cell
Figure 8.3 Signal transduction mechanisms at chemical synapses.
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11. Postsynaptic Potential
Change in membrane potential in response to neurotransmitter binding to receptor
A depolarization 去極化 is considered an excitation because it brings the membrane potential closer to the threshold to generate an action potential  excitatory synapse 興奮性突觸
A hyperpolarization 過及化 is considered an inhibition because it takes the membrane potential away from the threshold  inhibitory synapse 抑制性突觸
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12. Excitatory Synapses
A excitatory synapse is one that brings the membrane potential of the postsynaptic neuron closer to the threshold for generating an action potential  excitatory postsynaptic potential (EPSP)
EPSPs are graded potentials, with the amplitude of depolarization increasing as more neurotransmitters bind to receptors
Depending on the synapse, EPSPs can be fast or slow
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13. Excitatory Synapses P201 Figure 8.4 Excitatory synapses.
Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings.
Figure 8.4 Excitatory synapses.
The neurotransmitter opens ion channels, allowing Na+ to enter the cell and K+ to leave it  Na+ movement is greater, so that the net effect is a depolarization (an EPSP) lasting several milliseconds
Activation of a G protein by neurotransmitter leads to the series of events depicted  phosphorylation of the K+ channel in the final step decreases the leakage of K+ out of the cell, producing a depolarization lasting several seconds
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14. Inhibitory Synapses
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An inhibitory synapse is one that either takes the membrane potential of the postsynaptic neuron away from the action potential threshold by hyperpolarizing the neuron, or stabilizes the membrane potential at the resting value
An inhibitory synapse, the binding of a neurotransmitter to its receptors opens channels for either K+ or Cl- ions
When a neurotransmitter causes K+ channels to open, K+ will move out the cell, hyperpolarizing it  inhibitory postsynaptic potential (IPSP)
An IPSP, like an EPSP, is a graded potential
Figure 8.5 An inhibitory synapse involving potassium channels.
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15. IPSPs Are Graded Potentials
Higher frequency of action potentials
More neurotransmitter released
More neurotransmitter binds to receptors
to open (or close) channels
Greater increase (or decrease) ion permeability
Greater (or lesser) ion flux
Greater hyperpolarization
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16. Inhibitory Synapses
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In a neuron in which chloride ions are actively transported out of the cell  Cl- is concentrated in the extracellular fluid
When chloride channels are opened by neurotransmitters binding to receptors  Cl- moves into the cell  producing a hyperpolarization or an IPSP
Figure 8.6 The roles of chloride channels in inhibitory synapses. P

17. Inhibitory Synapses P202-203
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Cells that lack Cl- transporters have Cl- leak channels, and Cl- is at equilibrium across their membranes
If binding of neurotransmitter 1 (NT1) causes more Cl- channels to open  no net movement of  occurs  because Cl- is already at equilibrium (b)
If NT1 is present at an inhibitory synapse while NT2 is present at an excitatory synapse  Cl- will move into the cell at the same time that positive charges enter the channel open by NT2  opposing any change in membrane potential
The result is that the EPSP will be diminished, or may even be absent  stabilize the membrane potential  is considered an inhibitory action because it decreases the likelihood that the neuron will reach threshold for an action potential
Figure 8.6 The roles of chloride channels in inhibitory synapses. P

18. III. Neural Integration
A given neuron receives communication from many neurons, an arrangement called convergence
The axon hillock of the postsynaptic neuron acts as an integrator that in effect adds up all the signals arriving from all active synapses  neural integration
Figure 8.7 Divergence and convergence. P

19. Summation
The summing of input from various synapses at the axon hillock of the postsynaptic neuron to determine whether the neuron will generate action potentials
Because EPSPs and IPSPs are graded potentials, they are capable of being added together  summation
This summation can be either spatial or temporal, depending on whether the postsynaptic potentials being summed arise at the same synapse or at different synapses
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20. Temporal Summation From the Same Synapse
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(a)
(b)
Figure 8.8 Temporal and spatial summation.
A postsynaptic neuron receiving excitatory input from neurons A and B, and inhibitory input from neuron C; three different neurotransmitters are involved (a)
If the sum of all synaptic potentials at the axon hillock results in depolarization to threshold, then an action potential is generated (a)
Temporal summation occurs when action potentials arriving from a presynaptic axon terminal of neuron A occur close enough together in time such that the EPSPs produced in response to the binding of neurotransmitter overlap and sum (b) P

21. Spatial Summation From Different Synapses
Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings.
(a)
(c)
Figure 8.8 Temporal and spatial summation.
A postsynaptic neuron receiving excitatory input from neurons A and B, and inhibitory input from neuron C; three different neurotransmitters are involved (a)
Spatial summation occurs when different synapses are simultaneously active (c)
If EPSPs from synapses with neurons A and B occur at the same time, the EPSPs sum and reach threshold, triggering an action potential
Note that if synapses with neurons A and C were simultaneously active, the resulting IPSP and EPSP would tend to cancel each other out, producing little change in membrane potential
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22. Frequency Coding
Strength of depolarization at the axon hillock is coded by the frequency of action potentials
Increases in the strength of such supra-threshold stimuli cause the frequency of action potentials to increase, an effect called frequency coding
A higher frequency of action potentials corresponds to stronger communication to the next neuron in a neural pathway
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23. IV. Presynaptic Modulation
Axo-axonic synapses = modulatory synapses
Regulate communication between a presynaptic neuron with a postsynaptic neuron
Two types:
Presynaptic facilitation  the release of neurotransmitter is enhanced
Presynaptic inhibition  the release of neurotransmitter is decreased
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24. Chemical Synapse Presynaptic Neuron Postsynaptic Neuron Modulating
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25. Presynaptic Facilitation
Figure 8.9 Presynaptic modulation at axoaxonic synapses.
When neurons C and E are both active, neurotransmitter from neuron E enhances the release of neurotransmitter C, increasing the strength of the resulting EPSP to threshold and generating an action potential in neuron X P

26. Presynaptic Inhibition
Figure 8.9 Presynaptic modulation at axoaxonic synapses.
When neurons F and H are both active, neurotransmitter from neuron H decreases the release of neurotransmitter F, decreasing the strength of the EPSP in neuron Y
When neurons F and G are both active, their EPSPs sum spatially, and neuron Y is depolarized to threshold, generating an action potential
When neurons F, G, and H are all activated, the EPSP from neuron F is diminished due to presynaptic inhibition by neuron H, such that the sum of the EPSPs from neurons F and G is sub-threshold, and an action potential is not generated P

27. V. Neurotransmitters: Structure, Synthesis, and DegradationP

28. Acetylcholine
Acetylcholine (Ach) is released from neurons in both central (CNS) and peripheral nervous systems (PNS)
It is the most abundant neurotransmitter in the PNS, where it is found in efferent neurons of both somatic and autonomic branches
Ach is synthesizes in the cytoplasm of the axon terminals of neurons
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29. Cholinergic Synapse P207-208
The enzyme choline acetyl transferase (CAT) catalyzes the reaction combining acetyl CoA with choline to form Ach ()
The Ach is then actively packaged into synaptic vesicles () until an action potential triggers its released by exocytosis ()
Once released, Ach may bind to cholinergic receptors on the postsynaptic cell () or be degraded by the enzyme acetylcholinesterase (AchE) into choline and acetate ()
Choline is actively transported back into the presynaptic neuron (), where it can be used to synthesize more Ach
Figure Neurotransmitter synthesis, action, and degradation at cholinergic synapses. P

30. Cholinergic Receptors
Cells in the nervous system commonly have different types of receptors for a specific neurotransmitter
Receptors for Ach are two types: nicotinic & muscarinic
Nicotinic receptors are ionotropic & are located in several areas of the PNS (autonomic & somatic) and in some regions of the CNS
Muscarinic receptors are metabotropic & are found on some effector organs for the autonomic nervous system (ANS), are the dominant cholinergic receptor type found in the CNS
Even though these receptors share a common messenger—Ach—the effects on the postsynaptic cell are very different  the action of chemical messenger ultimately depends, not on the nature of the messenger, but on the type of receptor to which the messenger binds on the target cell
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31. P
Figure Signal transduction mechanisms at cholinergic receptors.
Nicotinic receptors are receptor-operated channels that permit both Na+ and K+ ions to move through
When Ach binds to these receptors, the channel open  because more Na+ moves in than K+ move, the result is an EPSP
Muscarinic receptors are couple to G proteins that can either directly open/close ion channels or activate/inhibit an enzyme that catalyzes the production of a second messenger
The second messengers produced can have a variety of effects on the postsynaptic cell, including opening or closing ion channels  excitatory (EPSPs) or inhibitory (IPSPs)

32. Biogenic Amines Derived from amino acids
Catecholamines - derived from tyrosine
Dopamine
Norepinephrine
Epinephrine
Serotonin - derived from tryptophan
Histamine - derived from histidine
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33. Synthesis, Release and Degradation of Biogenic Amines
Cytosol of axon terminal
Packaged into synaptic vesicles
Release trigger by action potential  exocytosis
Release
Dopamine and norepinephrine common in CNS
Norepinephrine also in PNS
Epinephrine from CNS, but more commonly released from adrenal medulla as hormone
Enzymes for degrading biogenic amines
Monoamine Oxidase (MAO)--is located in the synaptic cleft, in the axon terminal of the neurons that release the catecholamines, and in some glial cell
Catechol-O-methyltransferase (COMT)--is located in the synaptic cleft P

34. Adrenergic Receptors
Receptors for epinephrine and norepinephrine are called adrenergic receptors, of which there are two main classes: alpha (a) & beta (b)
Adrenergic receptors are G protein coupled
Generally linked to second messengers
Alpha adrenergic Receptors greatest affinity for norepinephrine
Alpha 1
Alpha 2
Beta adrenergic Receptors
Beta 1
Beta 2 greatest affinity for epinephrine
Beta 3
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35. Serotonin Histamine CNS neurotransmitter Main location  brainstem
Functions  regulating sleep; emotions
Histamine
CNS neurotransmitter
Main location  hypothalamus
More commonly known for paracrine actions
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36. Amino Acid Neurotransmitters
Amino Acid NTs at Excitatory Synapses
Aspartate
Glutamate
Amino Acid NTs at Inhibitory Synapses
Glycine
GABA
Figure The amino acid neurotransmitters. P

37. Neuropeptides Short chains of amino acids Examples
Endogenous opiates  endorphins, dynorphins, enkephalins
Vasopressin
Substance P
VIP = Vasoactive Intestinal Peptide
Neurotensin
CCK = Cholecystokinin
TRH = thyrotropin releasing hormone
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38. Other Neurotransmitters
Purines
ATP
NO = Nitric Oxide
Gas
Nitric oxide synthetase P