Neurophysiology – lecture 22

April 5, 2011

1 Review:
1. The general concept in action potential propagation is that:
A.P. in axon segment A → depolarization of axon segment B → A.P. in axon segment B → depolar-
ization of axon segment C → A.P. in axon segment C → etc.
2. That is, action potential “propagation” is really a sequence of independent A.P.s with each A.P.
triggering a preceding A.P.
3. This model also applies to action potentials propagated along myelinated axons with slight modifica-
tions:
(a) the layers of myelin surrounding the axon act as a large resistance between the inside and the
outside of the axon.
(b) this myelin resistance is in series with the axon membrane resistance.
(c) Hence, only a small fraction of the transmembrane potential, i.e., the difference in voltage between
the inside of the axon and the extracellular fluid outside the myelinated axon, is across the axon
membrane in the myelinated portions of the axon.
4. However, at Nodes of Ranvier the entire difference in voltage between the inside of the axon and the
extracellular fluid outside the cell is across the axon membrane.
5. Hence during a propagated A.P. only the axon membrane at the Nodes of Ranvier gets depolarized
sufficiently to elicit an A.P. which occurs at that node only.
6. This localization of A.P. production to nodes is also guaranteed by the fact that voltage-dependent
Na+ channels are only localized to the Nodes of Ranvier.
7. This localization was verified by the fact that Tasaki saw voltage-dependent currents associated with
A.P. production only at Nodes of Ranvier along a myelinated. axon.
8. It is important to note that many (8 to 50) adjacent nodes are simultaneously involved in A.P. produc-
tion whenever an A.P. has been generated at any one spot along the axon. A.P.s do not “skip” from
one Node to another.
9. Myelinated axons have advantages over unmyelinated axons in that:
(a) They occupy less volume in the nervous system while conducting A.P.s with the same speed as
an unmeyrlinated axon.
(b) The capacitance along myelinated sections on the axon is much less than the capacitance along
unmyelinated sections of axon, so depolarization occurs more rapidly along myelinated axons

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 than along unmyelinated axons. Consequently, A.P.s are conducted along myelinated axons more
rapidly than along unmyelinated axons.
(c) Less inward Na+ current is needed to generate a propagated A.P. in a myelinated axon than in
an unmyelinated axon, so myelinated axons consume less ATP per A.P. than do unmyelinated
axons.

2 Mechanisms of synaptic transmission

1. Synaptic transmission is here defined as the mechanisms used to transfer information from one neuron
in close contact with another neuron.

3 General Electrical considerations concerning synaptic transmis-

sion.
1. During A.P. propagation along an axon we have seen that the net inward current produced at one
segment along an axon is returned to the extracellular medium as outward capacitive current along
that segments membrane, but also some of that current passes through the longitudinal resistance, ri
, to an adjacent axon segment to charge its membrane more positively and depolarize this segment of
adjacent membrane.
The result of this is that an A.P. gets produced in this segment shortly after the A.P. produced in the
first segment of axon.
2. On the other hand if 2 axons abut one another at their ends so that the ends of both axons were covered
with axon membrane separated by a small interstitial space between the axon ends, the outcome is
very different. In this case capacitive current leaves the membrane at the end of the axon during an
A.P. just as it does elsewhere along the axon membrane. Current thus entering the small interstitial
space between the axon ends can follow either of 2 current paths:
1) it can flow across the membrane of the second axon as capacitive and resistive current into the
second cell or
2) it can flow out to the extracellular fluid surrounding the first axon by flowing through the extra-
cellular fluid which occupies the small interstitial space between the axons.
3. Estimates from the modeling of axon membranes and conductance measurements show that nearly all
of this current will flow through the small interstitial space whose resistance is much lower than that
involved in the passage of current through the abutting axon membrane. As confirmation of this, when
an A.P. is produced in one unmyelinated axon no change in transmembrane potential is recorded in
an adjacent unmyelinated axon.
4. However, as Tom Kessler pointed out there are situations in which A.P.s produced in one neuron or
axon produce depolarizations in an adjacent neuron or axon by means of what are called “Electrical
Synapses”.
5. In consideration of the 2 situations described above, it should be clear that for an A.P. in one neuron
or axon to change the transmembrane potential in another neuron or axon there must be a relatively
low resistance pathway for current to flow between the 2 neurons or axons. The existence of such
a relatively low resistance pathway then determines whether or not there is an “Electrical Synapse”
present.

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 6. The presence of such a relatively low resistance pathway can be determined by using microelectrodes to
record from both neurons or both axons simultaneously. If current is passed through a microelectrode
in neuron A or axon A and a hyperpolarization of say -20mV is produced in neuron A or axon A, while
at the same time a hyperpolarization of say -8mV is produced in neuron B or axon B the we have
evidence the 2 neurons or axons are “electrically coupled”, i.e., there is an electrical synapse between
them.
7. In the case sited above the 2 neurons or axons would be described as having a “Coupling ratio” of
-8mV/-20mV = 0.4.
8. It is noteworthy that A.P.s produce depolarizations, say 100mV, that are much larger than their
threshold for producing A.P.s, say 15mV. Using this example, 100mV/15mV is considered their “Safety
Factor” = 6.7. Conversely, their coupling ratio would have to exceed 0.15 in order for a postsynaptic
A.P. to be generated.

4 Examples of electrical synapses and their function

1. In the ventral nerve cord of the earthworm:
The earthworm is a segmented worm. In segmented worms neurons found in one segment do not extend
their dendrites or axons into other segments; i.e., they are entirely contained in individual segments.
Despite this segmentation if you tickle either end of the worm, the entire worm, all 40 to 60 segments
contract or begin to wiggle. How does one segment communicate with other segments to produce this
generalized response?
Each segment contains 3 giant axons (Figure 15A) which run the full width of the segment. Each of
these giant axons abuts at both ends of the segment with a similar giant axon in the next anterior
segment and the next posterior segment. Where the giant fibers abut there is an electrical synapse
between them. Thus A.P.s that induce contraction and wiggling in each segment are propagated
along the giant axons by depolarizing successive giant axons through electrical synapses. While this
arrangement does not produce A.P. propagation along the giant axon pathway as rapidly as if the
length of the organism were served by 3 long axons, it does convey A.P.s rather rapidly and provide
an effective escape mechanism - go try to catch an earthworm that is only half way out of the ground.
So electrical synapses serve some places for rapid A.P. propagation between neurons or axons.
2. The crayfish and other invertebrates have a giant fiber (axon) system to rapidly effect escape responses
when needed. In the crayfish the giant fiber in the ventral nerve cord synapses electrically with axons
from motor neurons that innervate muscle fibers in the crayfishs legs and tail. (See Figure 15B.) A
current pulse to the giant fiber to depolarize it above threshold also depolarizes the postsynaptic motor
neuron axon leading to an A.P. in the motor neuron axon. The delay between the presynaptic A.P. and
the postsynaptic A.P. is only about 0.1ms. (At chemical synapses synaptic delays are generally on the
order of several milliseconds.) Thus, electrical synapses can provide a means of very rapid synaptic
transmission. This property can be very important as a means of speeding up escape responses.
3. There are many examples of electrical synapses used to synchronize activity in neurons and muscle
fibers.
(a) For instance muscle fibers in the heart contract simultaneously to produce the heart beat and
provide the contractual force which drives blood through the vascular system. This synchrony
is achieved by means of electrical synapses between heart muscle fibers. If this synchrony is lost
(fibrillation) the heart muscle fibers contract in an uncoordinated fashion and little or no blood
is driven through the vascular system.

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 (b) Certain rhythms visible in the EEG, like theta rhythm in the ippocampus, require electrical
coupling between neurons to synchronously produce potentials across large areas of the brain.
(c) The movements of your eyes when moving rapidly from one fixation point to another are facilitated
by the fact that some motor neurons in the oculomotor nucleus are electrically coupled and so
produce A.P.s synchronously resulting in a rapid contraction of the muscles which move the eye
ball.

5 Anatomical correlates of electrical synapses

1. Where electrical synapses have been found a particular anatomical structure called a “gap junction”
has also been found. (See Figure 15D.)
2. Gap junctions are characterized by an unusually close apposition of the pre- and post-synaptic mem-
branes. The distance between these membranes is only 3.5nm whereas elsewhere the distance between
the membranes of adjacent cells is more on the order of 20nm. The membranes at gap junctions are
also unusually straight and parallel to one another.
3. The membrane at the gap junction contains an almost geometrical array of “connexons”. Connexons
are transmembrane spanning and contain a central pore filled with water just like other channels which
we have encountered. Connexons are formed from 6 subunits which surround the central pore. Each
subunit is composed of a protein molecule called “connexin”.
4. Since each connexon only spans one membrane, it is necessary for 2 connexons - one in the presynaptic
membrane and one in the postsynaptic membrane - to be exactly apposed to one another to form a
complete channel and pore from one neuron to the other. (This arrangement is illustrated in an insert
in Figure 15D.)
5. The pore in the center of the connexon is rather large compared to the pores of Na+ and K+ channels
and it is not ion selective. In fact, compounds with molecular weights up to 350 can pass through these
channels. Thus, fluorescent dyes within this range of molecular weight can be injected or allowed to
diffuse from a microelectrode inserted in one of a pair of neurons coupled by a gap junction and that
dye will pass into the other coupled neuron and be visible there.
6. While gap junctions and hence electrical synapses are generally thought to be rather unchanging
entities, there is evidence that their functional properties can change. Experimentally, this has been
shown by altering the intracellular pH or [Ca2+ ]. Physiologically, this modulation appears to be
evident in the changing size of receptive fields in the retina. The structure of receptive fields is heavily
dependent on electrical synapses formed between a particular class of cells that lies parallel with the
surface of the retina and are called “horizontal cells”. During dark adaptation the size of these receptive
fields increases implying that the connectivity of these horizontal cells has also changed.