Neurons & the Nervous System
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The human nervous system
consists of billions of nerve cells (or neurons)plus supporting (neuroglial) cells. Neurons are able to
respond to stimuli (such as touch, sound, light, and so on), conduct impulses,
and communicate with each other (and with other types of cells like muscle
cells).
Nervous system
The nucleus of a neuron is located
in the cell body. Extending out from the cell body are processes called
dendrites and axons. These processes vary in number & relative length but
always serve to conduct impulses (with dendrites conducting impulses toward the
cell body and axons conducting impulses away from the cell body).
http://en.wikipedia.org/wiki/Image:Complete_neuron_cell_diagram_en.svg
Neurons can respond to stimuli and
conduct impulses because a membrane potential is established across the cell
membrane. In other words, there is an unequal distribution of ions (charged
atoms) on the two sides of a nerve cell membrane. This can be illustrated with
a voltmeter:
With one electrode placed inside a
neuron and the other outside, the voltmeter is 'measuring' the difference in
the distribution of ions on the inside versus the outside. And, in this
example, the voltmeter reads -70 mV (mV = millivolts). In other words, the
inside of the neuron is slightly negative relative to the outside. This
difference is referred to as the Resting Membrane Potential. How is this
potential established?
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The membranes of all nerve cells
have a potential difference across them, with the cell interior negative with
respect to the exterior (a). In neurons, stimuli can alter this potential
difference by opening sodium channels in the membrane. For example,
neurotransmitters interact specifically with sodium channels (or gates). So
sodium ions flow into the cell, reducing the voltage across the membrane.
Once the potential difference
reaches a threshold voltage, the reduced voltage causes hundreds of sodium
gates in that region of the membrane to open briefly. Sodium ions flood into
the cell, completely depolarizing the membrane (b). This opens more
voltage-gated ion channels in the adjacent membrane, and so a wave of
depolarization courses along the cell — the action potential.
As the action potential nears its
peak, the sodium gates close, and potassium gates open, allowing ions to flow
out of the cell to restore the normal potential of the membrane (c) (Gutkin
and Ermentrout 2006).
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Establishment of the Resting
Membrane Potential
Membranes are polarized or, in other
words, exhibit a RESTING MEMBRANE POTENTIAL. This means that there is an
unequal distribution of ions (atoms with a positive or negative charge) on the
two sides of the nerve cell membrane. This POTENTIAL generally measures about
70 millivolts (with the INSIDE of the membrane negative with respect to the
outside). So, the RESTING MEMBRANE POTENTIAL is expressed as -70 mV, and the
minus means that the inside is negative relative to (or compared to) the
outside. It is called a RESTING potential because it occurs when a membrane is
not being stimulated or conducting impulses (in other words, it's resting).
Neuron resting potential
What factors contribute to this
membrane potential?
Two ions are responsible: sodium
(Na+) and potassium (K+). An unequal distribution of these two ions occurs on
the two sides of a nerve cell membrane because carriers actively transport
these two ions: sodium from the inside to the outside and potassium from the
outside to the inside. AS A RESULT of this active transport mechanism (commonly
referred to as the SODIUM - POTASSIUM PUMP), there is a higher concentration of sodium on the outside
than the inside and a higher concentration of potassium on the inside than the
outside (Animation: How the Sodium-Potassium Pump Works).
Sodium-Potassium pump
The nerve cell membrane also
contains special passageways for these two ions that are commonly referred to
as GATES or 
CHANNELS.
Thus, there are SODIUM GATES and POTASSIUM GATES. These gates represent the
only way that these ions can diffuse through a nerve cell membrane. IN A
RESTING NERVE CELL MEMBRANE, all the sodium gates are closed and some of the
potassium gates are open. AS A RESULT, sodium cannot diffuse through the
membrane & largely remains outside the membrane. HOWEVER, some potassium
ions are able to diffuse out.
CHANNELS.
Thus, there are SODIUM GATES and POTASSIUM GATES. These gates represent the
only way that these ions can diffuse through a nerve cell membrane. IN A
RESTING NERVE CELL MEMBRANE, all the sodium gates are closed and some of the
potassium gates are open. AS A RESULT, sodium cannot diffuse through the
membrane & largely remains outside the membrane. HOWEVER, some potassium
ions are able to diffuse out.
OVERALL, therefore, there are lots
of positively charged potassium ions just inside the membrane and lots of
positively charged sodium ions PLUS some potassium ions on the outside. THIS
MEANS THAT THERE ARE MORE POSITIVE CHARGES ON THE OUTSIDE THAN ON THE INSIDE.
In other words, there is an unequal distribution of ions or a resting membrane
potential. This potential will be maintained until the membrane is disturbed or
stimulated. Then, if it's a sufficiently strong stimulus, an action potential
will occur.
Potassium channel
Voltage
sensing in a potassium ion channel. a, The control of ion flow through
voltage-gated channels is very sensitive to the voltage
across the cell membrane. By comparison, an electronic device such as a transistor is much less sensitive to applied voltage.
b, MacKinnon and colleagues (Zhou et al. 2001) have found that the voltage sensors in a bacterial potassium channel are charged 'paddles'
that move through the fluid membrane interior. Four voltage sensors (two of which are shown here) are linked mechanically to
the channel's 'gate'. Each voltage sensor has four tethered positive charges (amino acids); the high sensitivity of
channel gating results from the transport of so many charges, 16 in all, most of the way across the membrane (From: Sigworth 2003).
across the cell membrane. By comparison, an electronic device such as a transistor is much less sensitive to applied voltage.
b, MacKinnon and colleagues (Zhou et al. 2001) have found that the voltage sensors in a bacterial potassium channel are charged 'paddles'
that move through the fluid membrane interior. Four voltage sensors (two of which are shown here) are linked mechanically to
the channel's 'gate'. Each voltage sensor has four tethered positive charges (amino acids); the high sensitivity of
channel gating results from the transport of so many charges, 16 in all, most of the way across the membrane (From: Sigworth 2003).
In
a cross section view of the voltage-dependent potassium channel,
two of the four paddles move up and down, opening and closing the
central pore through which potassium ions flow out of the cell, restoring the
cell's normal negative inside, positive outside polarity.
two of the four paddles move up and down, opening and closing the
central pore through which potassium ions flow out of the cell, restoring the
cell's normal negative inside, positive outside polarity.
An action potential is a very rapid
change in membrane potential that occurs when a nerve cell membrane is
stimulated. Specifically, the membrane potential goes from the resting
potential (typically -70 mV) to some positive value (typically about +30 mV) in
a very short period of time (just a few milliseconds).
What causes this change in potential
to occur? The stimulus causes the sodium gates (or channels) to
open and, because there's more sodium on
the outside than the inside of the membrane, sodium then diffuses rapidly into
the nerve cell. All these positively-charged sodiums rushing in causes the
membrane potential to become positive (the inside of the membrane is now
positive relative to the outside). The sodium channels open only briefly, then
close again.
The potassium channels then open,
and, because there is more potassium inside the membrane than outside,
positively-charged potassium ions diffuse out. As these positive ions go out,
the inside of the membrane once again becomes negative with respect to the
outside (Animation: Voltage-gated channels) .
Threshold stimulus & potential
- Action potentials occur only when the membrane in
stimulated (depolarized) enough so that sodium channels open completely.
The minimum stimulus needed to achieve an action potential is called the threshold
stimulus.
- The threshold stimulus causes the membrane potential to
become less negative (because a stimulus, no matter how small, causes a
few sodium channels to open and allows some positively-charged sodium ions
to diffuse in).
- If the membrane potential reaches the threshold potential (generally 5 - 15 mV less negative than the resting
potential), the voltage-regulated sodium channels all open. Sodium ions
rapidly diffuse inward, & depolarization occurs.
All-or-None Law - action potentials occur maximally or not at all. In other
words, there's no such thing as a partial or weak action potential. Either the
threshold potential is reached and an action potential occurs, or it isn't
reached and no action potential occurs.
Refractory periods:
ABSOLUTE -
- During an action potential, a second stimulus will not
produce a second action potential (no matter how strong that stimulus is)
- corresponds to the period when the sodium channels are
open (typically just a millisecond or less)
RELATIVE -
- Another action potential can be produced, but only if
the stimulus is greater than the threshold stimulus
- corresponds to the period when the potassium channels
are open (several milliseconds)
- the nerve cell membrane becomes progressively more
'sensitive' (easier to stimulate) as the relative refractory period
proceeds. So, it takes a very strong stimulus to cause an action
potential at the beginning of the relative refractory period, but only a slightly
above threshold stimulus to cause an action potential near the end of the
relative refractory period
The absolute refractory period
places a limit on the rate at which a neuron can conduct impulses, and the
relative refractory period permits variation in the rate at which a neuron
conducts impulses. Such variation is important because it is one of the ways by
which our nervous system recognizes differences in stimulus strength, e.g., dim
light = retinal cells conduct fewer impulses per second vs. brighter light =
retinal cells conduct more impulses per second.
How does the relative refractory
period permit variation in rate of impulse conduction? Let's assume that the
relative refractory period of a neuron is 20 milliseconds long and, further,
that the threshold stimulus for that neuron (as determined, for example, in a
lab experiment with that neuron) is 0.5 volt. If that neuron is continuously
stimulated at a level of 0.5 volt, then an action potential (and impulse) will
be generated every 20 milliseconds (because once an action potential has been
generated with a threshold stimulus [and ignoring the absolute refractory
period], another action potential cannot occur until the relative refractory
period is over). So, in this example, the rate of stimulation (and impulse
conduction) would be 50 per second (1 sec = 1000 ms; 1000 ms divided by 20 ms =
50).
If we increase the stimulus (e.g.,
from 0.5 volt to 1 volt), what happens to the rate at which action potentials
(and impulses) occur? Because 1 volt is an above-threshold stimulus, it means
that, once an actional potential has been generated, another one will occur in
less than 20 ms or, in other words, before the end of the relative
refractory period. Thus, in our example, the increased stimulus will increase
the rate of impulse conduction above 50 per second. Without more information,
it's not possible to calculate the exact rate. However, it's sufficient that
you understand that increasing stimulus strength will result in an increase in
the rate of impulse conduction.
Refractory periods
Impulse conduction - an impulse
is simply the movement of action potentials along a nerve cell. Action
potentials are localized (only affect a small area of nerve cell membrane). So,
when one occurs, only a small area of membrane depolarizes (or 'reverses'
potential). As a result, for a split second, areas of membrane adjacent to each
other have opposite charges (the depolarized membrane is negative on the
outside & positive on the inside, while the adjacent areas are still
positive on the outside and negative on the inside). An electrical circuit (or
'mini-circuit') develops between these oppositely-charged areas (or, in other
words, electrons flow between these areas). This 'mini-circuit' stimulates the
adjacent area and, therefore, an action potential occurs. This process repeats
itself and action potentials move down the nerve cell membrane. This 'movement'
of action potentials is called an impulse.
- impulses typically travel along neurons at a speed of
anywhere from 1 to 120 meters per second
- the speed of conduction can be influenced by:
- the diameter of a fiber
- the presence or absence of myelin
- Neurons with myelin (or myelinated neurons) conduct impulses much faster than those without
myelin.
 The myelin sheath (blue) surrounding axons (yellow) is produced by glial cells (Schwann cells in the PNS, oligodendrocytes in the CNS). These cells produce large membranous extensions that ensheath the axons in successive layers that are then compacted by exclusion of cytoplasm (black) to form the myelin sheath. The thickness of the myelin sheath (the number of wraps around the axon) is proportional to the axon's diameter.
Myelination, the process by which glial cells ensheath the
axons of neurons in layers of myelin, ensures the rapid conduction of
electrical impulses in the nervous system. The formation of myelin sheaths is
one of the most spectacular examples of cell-cell interaction and
coordination in nature. Myelin sheaths are formed by the vast membranous
extensions of glial cells: Schwann cells in the peripheral nervous system
(PNS) and oligodendrocytes in the central nervous system (CNS). The axon is
wrapped many times (like a Swiss roll) by these sheetlike membrane extensions
to form the final myelin sheath, or internode. Internodes can be as long as 1
mm and are separated from their neighbors by a short gap (the node of
Ranvier) of 1 micrometer. The concentration of voltage-dependent sodium
channels in the axon membrane at the node, and the high electrical resistance
of the multilayered myelin sheath, ensure that action potentials jump from
node to node (a process termed "saltatory conduction")
(ffrench-Constant 2004).
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Schwann cells (or oligodendrocytes)
are located at regular intervals along the process (axons and, for some
neurons, dendrites) & so a section of a myelinated axon would look like
this:
Between areas of myelin are
non-myelinated areas called the nodes of Ranvier. Because fat (myelin) acts as
an insulator, membrane coated with myelin will not conduct an impulse. So, in a
myelinated neuron, action potentials only occur along the nodes and, therefore, impulses 'jump' over the areas of myelin -
going from node to node in a process called saltatory conduction
(with the word saltatory meaning 'jumping'):
Because the impulse 'jumps' over areas of myelin, an impulse travels much faster along a myelinated neuron
than along a non-myelinated neuron.
Impulse conduction and Schwann cells
 Multipolar neuron |
 Unipolar neuron |
 Bipolar neuron |
Multipolar neurons are so-named because they have many (multi-) processes that
extend from the cell body: lots of dendrites plus a single axon. Functionally,
these neurons are either motor (conducting impulses that will cause activity
such as the contraction of muscles) or association (conducting impulses and
permitting 'communication' between neurons within the central nervous system).
Unipolar neurons have but one process from the cell body. However, that
single, very short, process splits into longer processes (a dendrite plus an
axon). Unipolar neurons are sensory neurons - conducting impulses into the
central nervous system.
Bipolar neurons have two processes - one axon & one dendrite. These
neurons are also sensory. For example, biopolar neurons can be found in the retina
of the eye.
1 -
forming myelin sheaths
2 - protecting neurons (via phagocytosis)
3 - regulating the internal environment of neurons
in the central nervous system
2 - protecting neurons (via phagocytosis)
3 - regulating the internal environment of neurons
in the central nervous system
Synapse
= point of impulse transmission
between neurons; impulses are transmitted from pre-synaptic neurons to
post-synaptic neurons
Synapses
usually occur between the axon of a pre-synaptic neuron & a dendrite or
cell body of a post-synaptic neuron. At a synapse, the end of the axon is
'swollen' and referred to as an end bulb or synaptic knob. Within the end bulb
are found lots of synaptic vesicles (which contain neurotransmitter chemicals)
and mitochondria (which provide ATP to make more neurotransmitter). Between the
end bulb and the dendrite (or cell body) of the post-synaptic neuron, there is
a gap commonly referred to as the synaptic cleft. So, pre- and post-synaptic
membranes do not actually come in contact. That means that the impulse cannot
be transmitted directly. Rather, the impulse is transmitted by the release of
chemicals called chemical transmitters (or neurotransmitters).
Micrograph of a synapse (Schikorski and Stevens 2001).
Synaptic transmission
Post-synaptic membrane receptors
 Structural features of a typical nerve cell (i.e., neuron) and synapse. This drawing shows the major components of a typical neuron, including the cell body with the nucleus; the dendrites that receive signals from other neurons; and the axon that relays nerve signals to other neurons at a specialized structure called a synapse. When the nerve signal reaches the synapse, it causes the release of chemical messengers (i.e., neurotransmitters) from storage vesicles. The neurotransmitters travel across a minute gap between the cells and then interact with protein molecules (i.e., receptors) located in the membrane surrounding the signal-receiving neuron. This interaction causes biochemical reactions that result in the generation, or prevention, of a new nerve signal, depending on the type of neuron, neurotransmitter, and receptor involved (Goodlett and Horn 2001). |
Synapse
When an impulse arrives at the end bulb, the end bulb membrane becomes more permeable to calcium.
Calcium diffuses into the end bulb & activates enzymes that cause the
synaptic vesicles to move toward the synaptic cleft. Some vesicles fuse with
the membrane and release their neurotransmitter (a good example of exocytosis).
The neurotransmitter molecules diffuse across the cleft and fit into receptor
sites in the postsynaptic membrane. When these sites are filled, sodium
channels open & permit an inward diffusion of sodium ions. This, of course,
causes the membrane potential to become less negative (or, in other words, to
approach the threshold potential). If enough neurotransmitter is released, and
enough sodium channels are opened, then the membrane potential will reach
threshold. If so, an action potential occurs and spreads along the membrane of
the post-synaptic neuron (in other words, the impulse will be transmitted). Of
course, if insufficient neurotransmitter is released, the impulse will not be
transmitted.
Impulse transmission - The nerve impulse (action potential) travels down the presynaptic axon towards the synapse, where it activates voltage-gated calcium channels leading to calcium influx, which triggers the simultaneous release of neurotransmitter molecules from many synaptic vesicles by fusing the membranes of the vesicles to that of the nerve terminal. The neurotransmitter molecules diffuse across the synaptic cleft, bind briefly to receptors on the postsynaptic neuron to activate them, causing physiological responses that may be excitatory or inhibitory depending on the receptor. The neurotransmitter molecules are then either quickly pumped back into the presynaptic nerve terminal via transporters, are destroyed by enzymes near the receptors (e.g. breakdown of acetylcholine by cholinesterase), or diffuse into the surrounding area.
This describes what happens when an
'excitatory' neurotransmitter is released at a synapse. However, not all
neurotransmitters are 'excitatory.'
Types of neurotransmitters:
1- Excitatory - neurotransmitters that make membrane potential
less negative (via increased permeability of the membrane to sodium) &,
therefore, tend to 'excite' or stimulate the postsynaptic membrane
2 -
Inhibitory - neurotransmitters that make membrane potential more negative (via
increased permeability of the membrane to potassium) &, therefore, tend to
'inhibit' (or make less likely) the transmission of an impulse. One example of
an inhibitory neurotransmitter is gamma aminobutyric acid (GABA; shown below).
Medically, GABA has been used to treat both epilepsy and hypertension. Another
example of an inhibitory neurotransmitter is beta-endorphin, which results in
decreased pain perception by the CNS.
Neurotransmitters (acetylcholine described starting at about 2:55)
1 - Temporal summation - transmission of an impulse by rapid
stimulation of one or more pre-synaptic neurons
2 -
Spatial summation - transmission of an impulse by simultaneous or nearly
simultaneous stimulation of two or more pre-synaptic neurons
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