Chapter 3 - Synaptic Transmission Flashcards
1
Q
Ions
2 types
A
Ions–electrically charged molecules.
Anions are negatively charged.
Cations are positively charged.
2
Q
Ions are dissolved in _________ fluid, separated from the ___________ fluid by the ______________
A
Ions are dissolved in intracellular fluid, separated from the extracellular fluid by the cell membrane.
3
Q
Movement down the Axon
A
Orthodromic
Antidromic – backwards
4
Q
Electrical Synapses Work with No Time Delay
Diagram
Synaptic Transmission:
Sequence of Events:
A
- Action potential travels down the axon to the axon terminal.
- Voltage-gated calcium channels open and calcium ions (Ca2+) enter.
- Synaptic vesicles fuse with membrane and release transmitter into the cleft.
- Transmitters bind to postsynaptic receptors and cause an EPSP or IPSP.
- EPSPs or IPSPs spread toward the postsynaptic axon hillock.
- Transmitter is inactivated or removed–action is brief.
- Transmitter may activate presynaptic autoreceptors, decreasing release
5
Q
Ligands
2 types
A
Ligands fit receptors exactly and activate or block them:
Endogenous ligands–neurotransmitters and hormones
Exogenous ligands–drugs and toxins from outside the body
6
Q
A Nicotinic Acetylcholine Receptor
A
Some chemicals can fit on cholinergic receptors and block the action of ACh:
Curare and bungarotoxin block ACh receptors–are antagonists
However, muscarine and nicotine mimic ACh and are agonists of the receptor.
7
Q
Receptors control ion channels in two ways:
A
Ionotropic receptors open when bound by a transmitter (also called a ligand-gated ion channel).
Metabotropic receptors recognize the transmitter but instead activate G-proteins and change intracellular activity.
8
Q
Pinocytosis
A
is the process of repackaging transmitter into vesicles.
9
Q
Types of synapses:
A
Axo-dendritic–axon terminal synapses on a dendrite
Axo-axonic–between two axons
Dendro-dendritic–between two dendrites
Retrograde–uses gas to signal presynaptic cell to release transmitter
10
Q
neurophysiology
A
The study of the life processes within neurons that use electrical and chemical signals.
A neuron at rest is a balance of electrochemical forces.
11
Q
We’ll learn that information flows within a neuron via ________ signals, while information passes between neurons through
_____________ _____________
A
Electrical
Chemical signals
12
Q
ion
A
An atom or molecule that has acquired an electrical charge by gaining or losing one or more electrons.
13
Q
anion
A
A negatively charged ion, such as a protein or chloride ion.
14
Q
intracellular fluid
A
Also called cytoplasm. The watery solution found within cells.
15
Q
extracellular fluid
A
The fluid in the spaces between cells (interstitial fluid) and in the vascular system.
16
Q
cell membrane
A
The lipid bilayer that ensheathes a cell.
17
Q
microelectrode
A
An especially small electrode used to record electrical potentials from living cells.
18
Q
resting membrane potential
A
A difference in electrical potential across the membrane of a nerve cell during an inactive period.
19
Q
millivolt (mV)
A
A thousandth of a volt.
20
Q
Living cells are more negative on the _____ than on the ________
A
Inside
Outside
21
Q
Of the many ions that a neuron contains, a majority are?
A
anions
22
Q
Can large protein anions that exit the cell?
A
no
23
Q
Where are the ions dissolved?
A
Intercellular fluid
24
Q
What is the measurement of resting membrane potential?
A
–60 mV (values may range between –50 and –80 mV)
thousandths of a volt, or millivolts (mV)
25
What divides the intercellular and extracellular fluid?
the cell membrane
26
Cell membranes are made up of?
lipid bilayer
27
sorts of specialized proteins in the lipid bilayer?
ion channel
28
Some ion channels stay _____ all the time.
open
29
the cell membrane of a neuron channels that selectively allow to cross the membrane.
potassium ions (K+)
30
What is the symbol for potassium and is it a positive or negative ion.
K+
31
If a cell membrane has selective permeability to potassium it ….
that is, K+ ions can enter or exit the cell fairly freely, while other ions are impeded by the cell membrane
32
The resting potential of the neuron reflects a balancing act between WHAT two opposing forces that drive K+ ions in and out of the neuron?
Diffusion
| electrostatic pressure
33
Diffusion
The spontaneous spread of molecules of one substance among molecules of another substance until a uniform concentration is achieved.
the force that causes molecules of a substance to diffuse from regions of high concentration to regions of low concentration.
34
negative polarity
A negative electrical-potential difference relative to a reference electrode.
35
lipid bilayer
The structure of the neuronal cell membrane, which consists of two layers of lipid molecules, within which float various specialized proteins, such as receptors.
36
ion channel
A pore in the cell membrane that permits the passage of certain ions through the membrane when the channels are open.
37
selective permeability
The property of a membrane that allows some substances to pass through, but not others.
38
concentration gradient
Variation of the concentration of a substance within a region.
39
Molecules tend to move down their ____________ ____________until they are evenly distributed.
concentration gradient
40
electrostatic pressure
The propensity of charged molecules or ions to move, via diffusion, toward areas with the opposite charge.
41
Because of electrostatic pressure positively charged ______ are thus ________ to the negatively charged interior of the cell; and conversely, ________ are ________by the cell interior and so tend to exit to the extracellular fluid.
Cations
Attracted
Anions
repelled
42
sodium-potassium pump
The energetically expensive mechanism that pushes sodium ions out of a cell, and potassium ions in.
It pumps three sodium ions (Na+) out of the cell for every two K+ ions pumped in.
43
sodium ion (Na+)
A sodium atom that carries a positive charge because it has lost one electron.
44
What is the symbol of a sodium ion? Is it positive or negatively charged?
Na+
45
In fact, a large fraction of the energy consumed by the brain is used to ….
Maintain the ionic differences across neuronal membranes.
46
How does the sodium-potassium pump causing a net buildup of negative charges inside the cell?
And how does the electrostatic pressure inside the cell compensate to create equilibrium
The sodium-potassium pump causes a buildup of K+ ions inside the cell, but recall that at rest the membrane is much more permeable to K+ ions than Na+ ions. That means K+ ions will tend to leave the interior, down their concentration gradient, causing a net buildup of negative charges inside the cell.
As negative charge builds up inside the cell, it begins to exert electrostatic pressure to pull positively charged K+ ions back inside.
47
Equilibrium
Here, the point at which the movement of ions across the cell membrane is balanced, as the electrostatic pressure pulling ions in one direction is offset by the diffusion force pushing them in the opposite direction.
48
Nernst equation
An equation predicting the voltage needed to just counterbalance the diffusion force pushing an ion across a semipermeable membrane from the side with a high concentration to the side with a low concentration.
49
action potential
The propagated electrical message of a neuron that travels along the axon to the presynaptic axon terminals.
The very brief but large changes in neuronal polarization, which are propagated at high speed along the axon.
(sometimes referred to as a spike because of its shape)
It is a rapid reversal of the membrane potential that momentarily makes the inside of the membrane positive with respect to the outside.
50
Hyperpolarization
An increase in membrane potential (the interior of the neuron becomes even more negative, relative to the outside)
51
So if the neuron already has a resting membrane potential of, say, –60 mV, hyperpolarization does what
makes it even farther from zero, maybe –70 mV
52
Depolarization
A reduction in membrane potential (the interior of the neuron becomes less negative).
In other words, depolarization of a neuron brings its membrane potential closer to zero.
53
What is the reverse of depolarization?
hyperpolarization
54
Capacitance
the distortions at the beginning and end of the neuron’s response are caused by the membrane’s ability to store electricity, known as capacitance
55
The greater the stimulus, the greater the response; so the neuron’s change in potential is called what?
graded response (only with passive graded potentials and not action potentials)
56
local potential
An electrical potential that is initiated by stimulation at a specific site, which is a graded response that spreads passively across the cell membrane, decreasing in strength with time and distance.
Local potentials are graded and diminish over time and distance, also arise at synapses in response to other neurons.
57
The application of depolarizing pulses to the membrane follows the same pattern as for hyperpolarizing stimuli, producing local, graded responses until when?
The stimulus depolarizes the cell to –40 mV or so (the exact value varies slightly among neurons). At this point, known as the threshold, a sudden and brief (0.5–2.0 millisecond [ms]) response the action potential is provoked
58
Threshold
The stimulus intensity that is just adequate to trigger an action potential. (–40 mV or so)
After which , a sudden and brief (0.5–2.0 millisecond [ms]) response the action potential is provoked.
59
How is the action potential unlike the passive graded potentials
the action potential is actively propagated (or regenerated) down the axon, through ionic mechanisms
60
all-or-none property
The fact that the amplitude of the action potential is independent of the magnitude of the stimulus.
Larger depolarizations produce more action potentials, not larger action potentials. In other words, the size (or amplitude) of the action potential is independent of stimulus magnitude.
61
Afterpotential
The positive or negative change in membrane potential that may follow an action potential.
electrical oscillations immediately following the spike; these changes
which are also related to the movement of ions in and out of the cell
62
voltage-gated Na+ channel
A Na+- selective channel that opens or closes in response to changes in the voltage of the local membrane potential; it mediates the action potential.
It is a tubular, membrane-spanning protein, but its central Na+-selective pore is ordinarily closed. When the cell membrane becomes depolarized to threshold levels, the channel’s shape changes, opening the pore to allow Na+ ions through.
the voltage-gated Na+ channel, is really quite a complicated machine. It monitors the axon’s polarity, and at threshold the channel changes its shape to open the pore, shutting down again just a millisecond later. The channel then “remembers” that it was recently open and refuses to open again for a short time. These properties produce and enforce the properties of the action potential.
63
Ionic mechanisms underlie the action potential
the action potential is created by the movement of sodium ions (Na+) into the cell, through channels in the membrane.
At its peak, the action potential approaches the equilibrium potential for Na+ as predicted by the Nernst equation: about +40 mV.
At this point, the concentration gradient pushing Na+ ions into the cell is exactly balanced by the positive charge pushing them out.
The action potential thus involves a rapid shift in membrane properties, switching suddenly from the potassium-dependent resting state to a primarily sodium-dependent active state, and then swiftly returning to the resting state.
This shift is accomplished through the actions of a very special ion channel: the voltage-gated Na+ channel.
64
English neurophysiologists Alan Hodgkin (1914–1998) and Andrew Huxley (1917–2012)
They established that the action potential is created by the move-
ment of sodium ions (Na+) into the cell, through channels in the membrane.
Studied squid axons
65
Why study the giant axon of the squid
More than half a millimeter in diameter, the squid’s giant axon is readily apparent to the naked eye and therefore much better suited to experimentation than mammalian axons.
Microelectrodes can be inserted into a giant axon without greatly altering the properties of the axon; it is even possible to push the intracellular fluid out of the squid axon and replace it with other fluids to study various properties of the action potential.
66
As long as the depolarization is below threshold, Na+ channels remain closed. But when the depolarization reaches threshold …
a few Na+ channels open at first, allowing ions to start entering the neuron, depolarizing the membrane even further and opening still more Na+ channels. Thus, the process accelerates until the barriers are removed and Na+ ions rush in.
67
By the time the voltage-gated Na+ channels close
The membrane potential has approached the sodium equilibrium potential of about +40 mV. Now, positive charges inside the nerve cell push K+ ions out, and voltage-gated K+ channels open, increasing the permeability to K+ even more, so the resting potential is quickly restored.
68
The upper limit to the frequency of action potentials becomes apparent at about …
1200 spikes per second.
69
Refractory
Transiently inactivated or exhausted.
Beyond a certain point, only the first stimulus is able to elicit an action potential. The axonal membrane is said to be refractory (unresponsive) to the second stimulus
The overall length of the refractory phase is what determines a neuron’s maximal rate of firing.
70
absolute refractory phase
A brief period of complete insensitivity to stimuli.
A brief period immediately following the production of an action potential, no amount of stimulation can induce another action potential, because the voltage-gated Na+ channels are either still open or unresponsive
71
relative refractory phase
A period of reduced sensitivity during which only strong stimulation produces an action potential, because K+ ions are still flowing out, so the cell is temporarily hyperpolarized after firing an action
potential
72
What are refractoriness two phases:
absolute refractory phase
| relative refractory phase
73
You might wonder if the repeated inrush of Na+ ions would allow them to build up, affecting the cell’s resting potential.
In fact, relatively few Na+ ions need to enter to change the membrane potential (Alle et al., 2009), and the K+ ions quickly restore the resting potential.
74
The cell membrane tends to repel water because…
is made up of fatty molecules
75
Why can’t ions in body fluids easily pass directly through neuronal membranes which are highly selective for particular types of ions?
Because ions in body fluids are usually surrounded by clusters of water molecules
76
Why can minor even minor alteration of channel functioning can cause serious health problems
Given the extreme precision with which these ion channels must operate
77
Channelopathy
A genetic abnormality of ion channels, causing a variety of symptoms.
Is a medical condition in which the form and function of ion
channels is altered as a result of mutation of the genes that encode those channels.
Sodium channelopathy—a problem with sodium channels—is associated with a variety of seizure disorders, as well as heritable muscle diseases and certain types of cardiac ailments.
78
tetrodotoxin (TTX) and saxitoxin
| (STX) selectively block
voltage-gated sodium channels,
| thereby preventing the production of action potentials; paralysis and death rapidly follow.
79
Tetrodotoxin
A toxin from puffer fish ovaries that blocks the voltage-gated sodium channel, preventing action potential conduction.
80
batrachotoxin,
A toxin, secreted by poison arrow frogs, that selectively interferes with Na+ channels
it forces Na+ channels to stay open, with lethal results.
81
How does the same specificity that makes channel toxins so deadly, makes them useful tools in the laboratory.
In the lab, these toxins have provided important clues about how those channels work
82
Why blocking channels isn’t always a bad thing.
Local anesthetics like lidocaine can be injected into nerves to block voltage-gated sodium channels, stopping action potentials that would otherwise signal pain to the brain.
83
In general, the transmission of action potentials is limited to _______
_______ ________ and ___________ usually have few voltage-gated Na+ channels, so they do not conduct action potentials.
axons
Cell bodies
Dendrites
84
The cell body and dendrites have very different ion channels then the axon. They are stimulated __________ at the __________.
chemically at the synapses
85
once an action potential starts at the ______ ________, the action potential regenerates itself down the length of the axon
axon hillock
86
How action potentials are actively propagated along the axon
another function for which voltage-gated channels are crucial
It is important to understand that the action potential is regenerated along the length of the axon.
the action potential is a spike of depolarizing electrical activity (with a peak of about +40 mV), so it strongly depolarizes the next adjacent axon segment. Because this adjacent segment is similarly covered with voltage-gated Na+ channels, the depolarization immediately creates a new action potential, which in turn depolarizes the next patch of membrane, which generates yet another action potential, and so on all down the length of the axon.
An analogy is the spread of fire along a row of closely spaced match heads in a matchbook. When one match is lit, its heat is enough to ignite the next match and so on along the row.
87
axon hillock
A cone-shaped area from which the axon originates out of the cell body. Functionally, the integration zone of the neuron.
88
Why does the axon normally conducts action potentials in only
one direction—from the axon hillock toward the axon terminals
because as it progresses along the axon, the action potential leaves in its wake a stretch of refractory membrane
also
Propagated activity does not spread from the axon hillock back over the cell body and dendrites, because the membranes there have very few voltage-gated Na+ channels, so they cannot produce an action potential.
89
the size of the action potential is _____ ________ at each point along the axon.
the same
90
conduction velocity
The speed at which an action potential is propagated along the length of an axon (or section of peripheral nerve).
It varies with the diameter of the axon. Larger axons allow the depolarization to spread faster through the interior.
91
nodes of Ranvier
A gap between successive segments of the myelin sheath where the axon membrane is exposed.
small gaps spaced about every millimeter along the axon
92
saltatory conduction
The form of conduction that is characteristic of myelinated axons, in which the action potential jumps from one node of Ranvier to the next.
because the myelin insulation offers considerable resistance to the flow of ionic currents across the membrane, the action potential jumps from node to node.
93
The evolution of rapid saltatory conduction in vertebrates has given them a major behavioral advantage over invertebrates, in which axons
are unmyelinated and mostly small in diameter, and thus slower in conduction.
94
neurotransmitter
Also called synaptic transmitter, chemical transmitter, or simply transmitter. The chemical released from the presynaptic axon terminal that serves as the basis of communication between neurons,
95
Synapses Cause_________, _________ changes in the Postsynaptic Membrane Potential
Graded
| Local
96
electrical synapses
Also called gap junction. The region between neurons where the presynaptic and postsynaptic membranes are so close that the action potential can jump to the postsynaptic membrane with-out first being translated into a chemical message.
the presynaptic membrane comes even closer to the postsynaptic membrane than it does at chemical synapses.
At electrical synapses, the facing membranes of the two cells have relatively large channels arranged to allow ions to flow from one neuron directly into the other.
As a consequence, the electrical current that is associated with neural activity in one neuron can flow directly across the gap junction to affect the other neuron.
Transmission at these synapses closely resembles action potential conduction along the axon.
Electrical synapses therefore work with practically no time delay, in contrast to chemical synapses, where the delay is on the order of a millisecond—slow in terms of neurons.
Because of the speed of their transmission, electrical synapses are frequently found in neural circuits that mediate escape behaviors in invertebrates.
They are also found where many fibers must be activated synchronously, as in the system for moving our eyes.
Clinically,
it is suspected that electrical synapses contribute to the spread of synchronized seizure discharges in epilepsy
97
postsynaptic potential
A local potential that is initiated by stimulation at a synapse, can vary in amplitude, and spreads passively across the cell membrane, decreasing in strength with time and distance.
Neurotransmitters released into synapses briefly alter the membrane potential of the postsynaptic cell.
98
excitatory postsynaptic potential (EPSP)
A depolarizing potential in the postsynaptic neuron that is caused by excitatory connections. EPSPs increase the probability that the postsynaptic neuron will fire an action potential.
99
A given neuron, receiving synapses from hundreds of other cells, is subject to _________ or _________ of ____________ ____________. When integrated, this massive array of local potentials determines whether the neuron will ______ _________ and therefore generate an ______ ___________ of its own.
A given neuron, receiving synapses from hundreds of other cells, is subject to hundreds or thousands of postsynaptic potentials. When integrated, this massive array of local potentials determines whether the neuron will reach threshold and therefore generate an action potential of its own.
100
It is important to remember that excitatory and inhibitory neurons get their names from their actions on ________ _______, not from their ________ ___ __________.
It is important to remember that excitatory and inhibitory neurons get their names from their actions on postsynaptic neurons, not from their effects on behavior.
101
Stimulation of an excitatory presynaptic neuron causes it to
produces an all-or-none action potential that spreads to the end of the axon, releasing transmitter.
102
Generally, the _________ _______of many excitatory synapses is needed to elicit an action potential in a ___________ ________.
combined effect
| postsynaptic neuron
103
synaptic delay
The brief delay between the arrival of an action potential at the axon terminal and the creation of a postsynaptic potential.
there is a delay: in the fastest cases, the postsynaptic depolarization begins about half a millisecond after the presynaptic action potentials arrive at the axon terminals.
This synaptic delay reflects the time needed for the neurotransmitter to be released and diffuse across the synaptic cleft,
104
inhibitory postsynaptic potential
| IPSP
A hyperpolarizing potential in the postsynaptic neuron that is caused by inhibitory connections. IPSPs decrease the probability that the postsynaptic neuron will fire an action potential.
When the inhibitory neuron is stimulated, the postsynaptic effect is an increase of the resting membrane potential. This hyperpolarization moves the cell membrane potential away from threshold—decreasing the probability that the neuron will fire an action potential
105
chloride ion (Cl –)
A chlorine atom that carries a negative charge because it has gained one electron.
Usually IPSPs result from the opening of channels that permit chloride ions (Cl –) to enter the cell. Because Cl– ions are much more concentrated outside the cell than inside (see Figure 3.4), they rush into the cell, making it even more negative.
106
The action potential of an inhibitory presynaptic neuron looks _______ _____ _____ __ ___ excitatory presynaptic neuron; all neurons use the ____ ____ of propagated signal.
The action potential of an inhibitory presynaptic neuron looks exactly like that of the excitatory presynaptic neuron; all neurons use the same kind of propagated signal
107
The nervous system treads a narrow path between overexcitation, which leads to ________, and underexcitation, which leads to _______ and _________.
Seizures
| coma and death
108
What determines whether a synapse excites or inhibits the postsynaptic cell?
One factor is the particular neurotransmitter released by the presynaptic cell.
The same neurotransmitter may be excitatory at one synapse and inhibitory at another, depending on the receptors present in the postsynaptic cell.
Transmitter chemicals that can be either depolarizing (excitatory) or hyperpolarizing (inhibitory).
The presynaptic terminals provide excitatory (depolarizing) or inhibitory (hyperpolarizing) stimulation to the postsynaptic cell membrane. If the membrane potential rises (depolarizes) above a threshold level, an action potential is fired.
109
Two types of summation
Spatial
| temporal
110
spatial summation
The summation at the axon hillock of postsynaptic potentials from across the cell body. If this summation reaches threshold, an action potential is triggered.
111
temporal summation
The summation of postsynaptic potentials that reach the axon hillock at different times. The closer in time that the potentials occur, the more complete the summation.
112
How do glial cells also play a role in synaptic transmission?
they increase the strength of the postsynaptic potential, overlying the presynaptic terminal and thereby preventing neurotransmitter from leaking out of the synaptic cleft.
113
8 step in Synaptic Transmission
1. The action potential traveling down the axon arrives at the axon terminal.
2. This depolarization opens voltage-gated calcium channels in the membrane of the axon terminal, allowing calcium ions (Ca2+ ) to enter the terminal.
3. The Ca2+ causes synaptic vesicles filled with neurotransmitter to fuse with the presynaptic membrane and rupture, releasing the transmitter molecules into the synaptic cleft.
4. Transmitter molecules cross the cleft to bind to special receptor molecules in the postsynaptic membrane, leading to the opening of ion channels in the postsynaptic membrane.
5. This ion flow creates a local EPSP or IPSP in the postsynaptic neuron.
6. Synaptic transmitter is either (a) inactivated (degraded) by enzymes or (b) removed from the synaptic cleft by transporters, so the transmission is brief and accurately reflects the activity of the presynaptic cell.
7. Synaptic transmitter may also activate presynaptic autoreceptors, regulating future transmitter release.
8. The IPSPs and EPSPs in the postsynaptic cell spread throughout its interior. If the integration of all the EPSPs and IPSPs depolarizes the axon hillock enough, the postsynaptic neuron will fire an action potential of its own. Now let’s examine these steps in detail.
114
calcium ion (Ca 2+)
A calcium atom that carries a double positive charge because it has lost two electrons.
115
exocytosis
The process by which a synaptic vesicle fuses with the presynaptic terminal membrane to release neurotransmitter into the synaptic cleft.
Synaptic vesicles are about 50 nanometers (nm) in diameter and are quite complex structures, with protein machinery to move the vesicles toward the synapse, where they fuse with the presynaptic membrane.
116
ligand
A substance that binds to receptor molecules, such as those at the surface of the cell.
Just as a particular key can open a door, a molecule of the correct shape, called a ligand, can fit into a receptor protein and activate or block it.
117
acetylcholine (ACh)
A neurotransmitter produced and released by parasympathetic postganglionic neurons, by motoneurons, and by neurons throughout the brain.
ACh acts on at least four kinds of cholinergic receptors; nicotinic and muscarinic are the two main kinds.
118
receptor molecule
Also called receptor. A protein that binds and reacts to molecules of a neurotransmitter or hormone.
119
Steps 2 and 3
| in Synaptic Transmission
2. This depolarization opens voltage-gated calcium channels in the membrane of the axon terminal, allowing calcium ions (Ca2+ ) to enter the terminal.
3. The Ca2+ causes synaptic vesicles filled with neurotransmitter to fuse with the presynaptic membrane and rupture, releasing the transmitter molecules into the synaptic cleft.
When an action potential reaches a presynaptic terminal, it opens voltage-gated calcium channels that allow an influx of calcium ions (Ca 2+), rather than K+ or Na+, into the axon terminal. These Ca2+ ions activate enzymes that cause vesicles near the presynaptic membrane to fuse with the membrane and discharge their contents into the synaptic cleft. The higher the frequency of action potentials arriving at the terminal, the greater the influx of Ca2+, and the more vesicles that dump transmitter into the synapse. Most synaptic delay is caused by the time needed for Ca2+ to enter the terminal. Both the diffusion of the transmitter across the cleft and the interaction of transmitter molecules with their receptors also take some time.
120
The rate of production of transmitter is governed by …
The rate of production of transmitter is governed by enzymes that are manufactured in the neuronal cell body and transported down the axons to the terminals. Intense activity of the neuron reduces the number of available vesicles, but soon more vesicles are produced to replace those that were discharged.
121
Explain how ACh can function as either an inhibitory or an excitatory neurotransmitter, at different synapses.
Each nicotinic ACh receptor consists of five subunits. The two ligand-binding sites normally bind ACh molecules, but they also bind exogenous ligands like nicotine and other nicotinic drugs.
122
endogenous ligand
Any substance, produced within the body, that selectively binds to the type of receptor that is under study.
123
exogenous ligand
Any substance, originating from outside the body, that selectively binds to the type of receptor that is under study.
124
curare
An alkaloid neurotoxin that causes paralysis by blocking acetylcholine receptors in muscle.
(exogenous ligand)
125
bungarotoxin
A neurotoxin, isolated from the venom of the banded krait, that selectively blocks acetylcholine receptors.
(exogenous ligand)
126
agonist
A molecule, usually a drug, that binds a receptor molecule and initiates a response like that of another molecule, usually a neurotransmitter.
Examples
carine and nicotine
127
antagonist
A molecule, usually a drug, that interferes with or prevents the action of a transmitter.
128
cholinergic
Referring to cells that use acetylcholine as their synaptic transmitter.
129
Various chemicals can fit onto receptor proteins and ______ the entrance of the key.
Block
130
Neurotransmitters and hormones made inside the body are examples of __________ ligands; drugs and toxins from outside the body are _________ ligands.
Endogenous
| exogenous
131
Some exogenous ligands
curare
| bungarotoxin
132
Lock and Key analogy
The action of a key in a lock is a good analogy for the action of a transmitter on a receptor protein. Just as a particular key can open a door, a molecule of the correct shape, called a ligand, can fit into a receptor protein and activate or block it
The lock-and-key analogy is strengthened by the observation that various chemicals can fit onto receptor proteins and block the entrance of the key. (endogenous ligands and exogenous ligands)
Just as there are master keys that fit many different locks, there are submaster keys that fit a certain group of locks, and keys that fit only a single lock. Similarly, each chemical transmitter binds to several different receptor molecules.
In the case of receptor-selective drugs, though, we have to think of keys (drug molecules) trying to insert themselves into all the locks (receptor molecules) in the neighborhood; each such key fits into only a particular subset of the locks. Once the drug (the key) binds to the receptor (the lock), it alters the activity of the receptor, activating it or blocking it. But the binding is usually temporary, and when the drug or transmitter breaks away from the receptor, the receptor returns to its unbound shape and functioning.
133
Nicotinic cholinergic receptors
found at synapses on muscles and in autonomic ganglia; it is the blockade of these receptors that is responsible for the paralysis caused by curare and bungarotoxin (see Box 3.1). Most nicotinic cholinergic synapses are excitatory, but there are also inhibitory nicotinic synapses
acetylcholine receptor
134
up-regulation
A compensatory increase in receptor availability at the synapses of a neuron.
135
down-regulation
A compensatory reduction in receptor availability at the synapses of a neuron.
136
ionotropic receptor
A receptor protein that includes an ion channel that is opened when the receptor is bound by an agonist.
A directly control an ion channel. When bound by the transmitter, the ion channel opens and ions flow across the membrane. (Ionotropic receptors are also known as chemically gated ion channels, or ligand-gated ion channels.)
137
ligand-gated ion channel
Also known as chemically gated ion channel. An ion channel that opens or closes in response to the pres-ence of a particular chemical.
138
metabotropic receptor
A receptor protein that does not contain an ion channel but may, when activated, use a G protein system to alter the functioning of the postsynaptic cell.
Recognize the synaptic transmitter, but they do not directly control ion channels. Instead, they activate molecules known as G proteins.
139
G proteins
A class of proteins that reside next to the intracellular portion of a receptor and that are activated when the receptor binds an appropriate ligand on the extracellular surface.
Are proteins that bind the compounds guanosine diphosphate (GDP), guanosine triphosphate (GTP), and other guanine nucleotides. Sometimes the G protein itself acts to open ion channels, but in other cases the G protein activates another, internal chemical signal to affect ion channels.
About 80% of the known neurotransmitters and hormones activate cellular signal mechanisms through receptors coupled to G proteins, so this coupling device is very important (Birnbaumer et al., 1990). The G protein is located on the inner side of the neuronal membrane. When a transmitter molecule binds to a receptor that is coupled to a G protein, parts of the G protein complex separate from each other.
140
second messenger
A slow-acting substance in the postsynaptic cell that amplifies the effects of synaptic activity and signals synaptic activity within the postsynaptic cell.
If we think of the neurotransmitter as the first, external messenger arriving at the receptor on the cell’s surface, then the next chemical signal, activated inside the cell, is a second messenger. Several different second messengers—such as cyclic adenosine monophosphate (cyclic AMP), diacylglycerol, or arachidonic acid—amplify the effect of the first messenger and can initiate processes that lead to changes in electrical potential at the membrane. An important feature of second-messenger systems is their ability to amplify and prolong the synaptic signals that a neuron receives.
141
In general, an increase in receptor numbers is referred to as ___________, and a process that decreases receptor density is called
_____________of that receptor type.
up-regulation
| down-regulation
142
The recognition of transmitter molecules by receptor molecules controls the opening of ion channels in two different ways.
Ionotropic receptors
| Metabotropic receptors
143
When a chemical transmitter such as ACh is released into the synaptic cleft, its post-synaptic action is not only prompt but usually very brief as well. This brevity ensures that the message is repeated faithfully. Accurate timing of synaptic transmission is necessary in …
many neural systems—for example, to drive the rapid cycles of muscle contraction and relaxation essential to many coordinated behaviors.
144
The prompt cessation of transmitter effects is achieved in one of two ways
1. Degradation. Transmitter can be rapidly broken down and thus inactivated by a special enzyme—a process known as degradation
2. Reuptake. Alternatively, transmitter molecules may be rapidly cleared from the synaptic cleft by being taken up into the presynaptic terminal—a process known as reuptake.
145
degradation
The chemical breakdown of a neurotransmitter into inactive metabolites.
Degradation. Transmitter can be rapidly broken down and thus inactivated by a special enzyme—a process known as degradation For example, the enzyme that inactivates ACh is acetylcholinesterase (AChE). AChE breaks down ACh very rapidly into choline and acetic acid, and these products are recycled (at least in part) to make more ACh in the axon terminal. AChE is found especially at synapses, but also elsewhere in the nervous system. Thus, if any ACh escapes from a synapse where it is released, it is unlikely to reach other synapses intact, where it could start false messages.
146
reuptake
The process by which released synaptic transmitter molecules are taken up and reused by the presynaptic neuron, thus stopping synaptic activity.
Reuptake. Alternatively, transmitter molecules may be rapidly cleared from the synaptic cleft by being taken up into the presynaptic terminal—a process known as reuptake. Norepinephrine, dopamine, and serotonin are examples of transmitters whose activity is terminated mainly by reuptake. In these cases, special receptors for the transmitter, called transporters, are located on the presynaptic axon terminal and bring the transmitter back inside. Once taken up into the presynaptic terminal, transmitter molecules may be repackaged into newly formed synaptic vesicles. Malfunction of reuptake mechanisms has been suspected to cause some kinds of mental illness, such as depression.
147
transporters
Specialized receptors in the presynaptic membrane that recognize transmitter molecules and return them to the presynaptic neuron for reuse.
148
autoreceptor
A receptor for a synaptic transmitter that is located in the presynaptic membrane, telling the axon terminal how much transmitter has been released.
Some neurotransmitter molecules never make it to the postsynaptic membrane. They may bind to receptors on the presynaptic membrane, a so-called autoreceptor. Through autoreceptors, the presynaptic cell is informed about the net concentration of transmitter in the synaptic cleft and may regulate future neurotransmitter release to adjust that concentration.
149
axo-dendritic
Referring to a synapse in which a presynaptic axon terminal synapses onto a dendrite of the postsynaptic neuron, either via a dendritic spine or directly onto the dendrite itself.
150
axo-somatic
Referring to a synapse in which a presynaptic axon terminal synapses onto the cell body (soma) of the postsynaptic neuron.
151
4 Different Types of Synaptic Connections
1. Most synapses are formed by an axon stimulating a dendrite (Axo-dendritic),
2. but axons also sometimes synapse upon cell bodies (Axo-somatic)
3. or even other axons (Axo-axonic)
4. And in some instances, specialized dendrites synapse upon other dendrites (Dendro-dendritic).
152
axo-axonic
Referring to a synapse in which a presynaptic axon terminal synapses onto another axon’s terminal.
153
retrograde synapse
A synapse in which a signal (usually a gas neurotransmitter) flows
from the postsynaptic neuron to the presynaptic neuron, thus counter to the usual direction of synaptic communication.
Transmission starts with classic axo-dendritic synaptic activity, but the postsynaptic cell subsequently releases a gas neurotransmitter, which signals the presynaptic cell to release more transmitter.
154
dendro-dendritic
Referring to a type of synapse in which a synaptic connection forms between the dendrites of two neurons.
allowing coordination of their activities
155
ectopic transmission
Cell-cell communication based on release of neurotransmitter in
regions outside traditional synapses.
Occurs between many neurons; in this mode of transmission, the location of transmitter release and the sites at which the transmitter acts are both well outside the conventional boundaries of nearby synapses
156
varicosity
The axonal swelling from which neurotransmitter diffuses in a nondirected synapse.
And throughout the brain are found axons with regular swellings, called varicosities, along their length; like a drip-irrigation system, these nondirected synapses steadily release neurotransmitter to broadly affect surrounding areas.
157
nondirected synapse
A type of synapse in which the presynaptic and postsynaptic cells
are not in close apposition; instead, neurotransmitter is released by axonal varicosities and diffuses away to affect wide regions of tissue.
158
neural chain
A simple kind of neural circuit in which neurons are attached linearly, end-to-end.
159
Circuits of Neurons: two kinds of processes
1. analog-like signals that vary in strength (such as graded potentials at synapses)
2. and digital-like, all-or-none signals (such as action potentials) that vary in frequency.
160
Neurons and Synapses Make Circuits
The nervous system comprises many different types of neural circuits to accomplish basic functions in cognition, emotion, and action—all the categories of behavior and experience.
161
knee jerk reflex
A variant of the stretch reflex in which stretching of the tendon beneath the knee leads to an upward kick of the leg.
For example, the basic circuit for the stretch reflex, such as the knee jerk reflex, consists of a sensory neuron, a motor neuron, and a single synapse where the sensory neuron communicates with the motor neuron. Note that this reflex is extremely rapid: only about 40 ms elapse between the stimulus and the initiation of the response.
162
Three factors account for this rapidity of the knee jerk reflex:
Electrical circuits can represent signals in either analog or digital ways— that is, in terms of continuously varying values or in terms of integers.
Neurons similarly feature two kinds of processes: analog-like signals that vary in strength (such as graded potentials at synapses)
digital-like, all-or-none signals (such as action potentials) that vary in frequency.
163
Two other features that are common to many kinds of neural circuits:
convergence and divergence
164
divergence
The phenomenon of neural connections in which one cell sends signals to many other cells.
165
convergence
The phenomenon of neural connections in which many cells send signals to a single cell.
166
electroencephalogram (EEG)
A recording of gross electrical activity of the brain recorded from large electrodes placed on the scalp.
167
epilepsy
A brain disorder marked by major sudden changes in the electrophysiological state of the brain that are referred to as seizures.
168
seizure
An epileptic episode.
Generalized seizures are characterized by loss of consciousness and symmetrical involvement of body musculature.
Seizures are an unfortunate manifestation of the electrical character of the nervous system. Because of the extensive connections among its nerve cells, the brain can generate massive waves of intense nerve cell activity that seem to involve almost the entire brain. In the normal, active brain, electrical activity tends to be desynchronized; that is, different brain regions carry on their functions more or less independently. In contrast, a seizure features widespread synchronization of electrical activity: broad swaths of the brain start firing in simultaneous waves of excitation,
Many abnormalities of the brain, such as trauma, injury, or metabolic problems, can predispose brain tissue to produce synchronized epileptiform activity, which can easily spread.
169
grand mal seizure
A type of generalized epileptic seizure in which nerve cells fire in high-frequency bursts.
Abnormal EEG activity is evident all over the brain. The person loses consciousness and makes characteristic movements: an enduring toniccontraction of the muscles for 1 or 2 minutes, followed by jerky, rhythmic clonic contractions and relaxations. Minutes or hours of confusion and sleep follow the seizure.
170
petit mal seizure
Also called an absence attack. A seizure that is characterized by a spike-and-wave EEG and often involves a loss of awareness and inability to recall events surrounding the seizure.
are a more subtle variant of generalized seizures, in which the
characteristic spike-and-wave EEG activity is evident for 5–15 seconds at a time, sometimes occurring many times per day. The person is unaware of the environment during these periods, and later cannot recall events that occurred during the petit mal episode. Behaviorally, the person does not show unusual muscle activity, except for a cessation of ongoing activity and sustained staring.
171
“spike-and-wave” pattern
| of brain activity
a seizure features widespread synchronization of electrical activity: broad swaths of the brain start firing in simultaneous waves of excitation, which are evident in the EEGs as an abnormal “spike-and-wave” pattern of brain activity.
172
complex partial seizure
In epilepsy, a type of seizure that doesn’t involve the entire brain and therefore can cause a wide variety of symptoms.
Do not involve the entire brain and thus can produce a wide variety of symptoms, often preceded by an unusual sensation, or aura.
173
Three types of seizures
grand mal seizure
petit mal seizure
complex partial seizure
174
aura
In epilepsy, the unusual sensations or premonition that may precede the beginning of a seizure.
175
kindling
A method of experimentally inducing an epileptic seizure by repeatedly stimulating a brain region.
In other words, the kindling stimulations somehow change the tissue and make it more epilepsy-prone. Interestingly, after years of epilepsy some human patients develop multiple foci for the initiation of seizures, perhaps because of a kindling process
176
event-related potential (ERP)
Also called evoked potential. Averaged EEG recordings measuring brain responses to repeated presentations of a stimulus. Components of the ERP tend to be reliable because the background noise of the cortex has been averaged out.
Gross potential changes evoked by discrete sensory stimuli, such as light flashes or clicks.
177
Controlling seizures
Many seizure disorders can be effectively controlled with the aid of antiepileptic drugs. Although these drugs have a wide variety of different targets, they have in common a tendency to selectively modulate the excitability of neurons, either by counteracting problems with ionic balance or by promoting inhibitory processes
178
Optogenetics
The use of genetic tools to induce neurons to become sensitive to light, such that experimenters can excite or inhibit the cell by stimulating it with light.
uses genetic tools to insert light-sensitive ion channels into neurons
so that stimulating the brain with light, delivered by fiber-optic cables, can excite or inhibit those targeted neurons
179
channelrhodopsin
A protein that, in response to light of the proper wavelength, opens a channel to admit sodium ions, which results in excitation of neurons.
The first opsin that was studied, channelrhodopsin, responds to blue light by allowing Na+ ions to enter the cell, depolarizing it
180
Halorhodopsin
A protein that, in response to light of the proper wavelength, opens a channel to admit chloride ions, which results in inhibition of neurons.
which when stimulated by yellow light, pumps Cl – ions
into the cell, hyperpolarizing it
181
calcium ion (Ca 2+
A calcium atom that carries a double positive charge because it has lost two electrons.
182
exocytosis
The process by which a synaptic vesicle fuses with the presynaptic terminal membrane to release neurotransmitter into the synaptic cleft.
183
ligand
A substance that binds to receptor molecules, such as those at the surface of the cell.
184
acetylcholine (ACh)
A neurotransmitter produced and released by parasympathetic postganglionic neurons, by motoneurons, and by neurons throughout the brain.
185
receptor molecule
Also called receptor. A protein that binds and reacts to molecules of a neurotransmitter or hormone.
186
the sequence and timing of events in the knee jerk reflex
Tap on patellar tendon stimulates stretch receptor in quadriceps muscle and starts chain of events.
Action potentials are triggered when threshold receptor potential reaches initial segment of sensory neuron.
Action potentials speed along large sensory neuron at about 100 m/s.
Action potentials in axon terminal cause release of synaptic transmitter glutamate. About 0.5 ms later, excitatory postsynaptic potential (EPSP) appears in motor neuron.
EPSP spreads passively to axon hillock, where it triggers action potentials.
Action potentials speed down large motor axon at about 100 m/s.
Action potentials reach neuromuscular junctions. ACh is released as the neurotransmitter.
Neuromuscular junction potential starts about 0.5 ms after arrival of presynaptic action potential. Action potentials are generated in the muscle fibers, which contract and cause leg to kick, about 40 ms after the hammer tap.
