Biocore 323
Fall 2010
Lecture 4: Nervous System Synaptic Transmission and Integration
Student Learning Objectives:
1. Students will be able to compare and contrast electrical and chemical synaptic transmission.
2. Students will be able to outline the steps in chemical synaptic transmission and predict changes in
the efficacy of transmission when the system is perturbed (e.g. changes in ion concentrations or
addition of drugs).
3. Students will understand the role of the neurotransmitter receptor in determining a
neurotransmitter’s effect on the post-synaptic cell.
4. Students will be able to predict the relative probability of action potential generation in the postsynaptic cell when given temporal and spatial summation data of EPSPs and IPSPs.
5. Students will be able to design experiments to measure the reversal potential at a synapse.
6. Students will be able to determine if a molecule is a neurotransmitter based on experimental data
about the behavior of that molecule.
7. Students will be able to describe basic mechanisms by which short-term and long-term changes to
synaptic efficacy are generated.
Key Terms & Concepts:
innervate
electrical synapse, gap junction
chemical synapse, synaptic cleft, neurotransmitter
synaptic knob, synaptic vesicle, exocytosis, quantal release, synaptic delay, sub-synaptic membrane
fast (direct) synaptic transmission: ligand-gated ion channel, reversal potential (Erev)
slow (indirect) synaptic transmission: ligand activated second messenger pathway
excitatory synapses: excitatory post-synaptic potential (EPSP)
inhibitory synapses: inhibitory post-synaptic potential (IPSP)
neuromuscular junction: motor endplate, junctional fold, end plate potential (epp)
synaptic summation: temporal, spatial
neuropeptides, neuromodulators, retrograde messengers
pre-synaptic facilitation and inhibition
convergence, divergence
Reading Assignment:
Text Review Questions:
Animal Physiology: Ch 2: 64-65; Ch 4: 122-137
Ch 4: 12-19
Biology: Ch 48: 1056-61
48.4: 1, 2, 3; self quiz: 4, 5, 6, 9
The World of the Cell: Ch 13: 380-88
13-1, 13-10, 13-11
Reading Questions:
1. Which type of synapse, electrical or chemical, conducts electrical signals from one cell to the
next most quickly? Which type of chemical synapse, direct or indirect, is faster?
Janet L. Branchaw, Ph.D.
Biocore 323
Fall 2010
2. How are neurotransmitters different from hormones as chemical messengers? How are they
different from neuromodulators?
3. Outline the steps involved in direct chemical synaptic transmission.
4. Compare direct and indirect chemical synaptic transmission.
5. Describe the ionic basis underlying excitatory post-synaptic potentials (EPSPs) and inhibitory
post-synaptic potentials (IPSPs) produced by direct chemical synaptic transmission.
6. Why does an increase in both Na+ and K+ conductance in the post-synaptic cell result in
depolarization of the membrane potential?
7. What is a post-synaptic current? How is it related to a post-synaptic potential? (Hint: Consider
Ohm’s Law.)
8. Why is the reversal potential in the post-synaptic cell at a synapse usually not equal to the
equilibrium potential for a single ion?
9. How can the same neurotransmitter produce an EPSP at one synapse and an IPSP at another?
10. Why are drugs that target neurotransmitter receptors powerful tools in the treatment of nervous
system disorders?
11. How does the distance of a dendrite or cell body synapse from the axon hillock impact that
synapse’s ability to influence whether the post-synaptic cell will generate an action potential?
12. T/F
One end plate potential (EPP) in a skeletal muscle fiber generates one action potential in
that fiber.
13. T/F
One excitatory post-synaptic potential (EPSP) in an -motor neuron cell body generates
one action potential in that neuron.
14. _______________ summation occurs when post-synaptic potentials occur in rapid succession at a
single synapse. The (longer / shorter) the time constant () of the membrane, the slower the decay
of post-synaptic potentials will be, and the more effective the summation can be. (circle)
15. _______________ summation occurs when post-synaptic potentials occur simultaneously at
different synapses. The (longer / shorter) the length constant () of the membrane, the farther
post-synaptic potentials will travel, and the more effective the summation can be. (circle)
16. What terms describe the anatomical arrangements among neurons that allow individual neurons
to receive input from multiple other neurons, and individual neurons to provide input to many
other neurons?
Janet L. Branchaw, Ph.D.
Biocore 323
Fall 2010
Group # _____
Group Name: ______________________________________________
Group Member Signatures:
1. ______________________
3. ______________________
2. ______________________
4. ______________________
Learning Objectives:
 Students will be able to explain the ionic basis of the resting membrane potential.
You have just joined a neuroscience research group that uses the squid giant axon as a model system.
To practice recording membrane potentials with sharp electrodes, your mentor asks you to design an
experiment to determine which ion the membrane is more permeable to at rest, Na+ or K+. All
experiments done in the lab are at room temperature, 18C (Note: At 18C, RT/zF = 58/z). The normal
concentrations of Na+ and K+ on the inside and outside of the squid giant axon are:
[Na+]o = 418 mM
[Na+]i = 64 mM
[K+]o = 10 mM
[K+]i = 302 mM
1. Your hypothesis (circle):
We hypothesize that the resting membrane in the squid giant axon is more permeable to (Na+/K+).
2. Experimental Design:
Test experiment –
Control experiment -
3. Predicted Results:
If our hypothesis is true, then we expect these results:
Janet L. Branchaw, Ph.D.
Biocore 323
Fall 2010
Group # _____
Group Name: ______________________________________________
Group Member Signatures:
1. ______________________
3. ______________________
2. ______________________
4. ______________________
Learning Objectives
Students will be able to predict the relative probability of action potential generation in the post-synaptic
cell when given temporal and spatial summation data of EPSPs and IPSPs.
In the figure below, there are two pre-synaptic neurons (A & B) and one postsynaptic neuron. The
postsynaptic cell resting membrane potential is -70 mV. T the amount of neurotransmitter released at
synapse A is equal to the amount released at synapse B, and both result in post synaptic potentials that are
10 msec. in duration. The synapses are equidistant (the same distance) from the recording electrode.
Ex= 62 log[X]o
z
[X]i
[Na+]o = 150 mM
[K+]o = 5 mM
[Cl-]o = 109 mM
[Na+]i = 15 mM
[K+]i = 150 mM
[Cl-]i = 8 mM
A. Calculate the equilibrium potential for each ion.
ENa =
EK =
(mV)
-65
Em (mV)
B. Activation of synapse A alone (indicated by
the arrow) causes an increase in postsynaptic
cell permeability to both Na+ and K+. On the
graph, draw the voltage response that would
be recorded in the postsynaptic cell when
synapse A is activated.
ECl =
-70
A
10
15
time
Janet L. Branchaw, Ph.D.
20
25
Biocore 323
Fall 2010
(mV)
Em (mV)
C. Activation of synapse B alone (indicated by
the arrow) causes an increase in postsynaptic
cell permeability to Cl-. On the graph, draw
the voltage response that would be recorded
in the postsynaptic cell when synapse B is
activated.
-70
B
10
15
20
2
time (ms)
(mV)
-65
Em (mV)
D. When synapses A & B are activated
simultaneously (indicated by the arrow),
inputs from the two synapses sum together.
On the graph, draw the voltage response that
would be recorded in the postsynaptic cell
when synapses A & B are activated
simultaneously.
-70
A+B
10
15
time (ms)
Janet L. Branchaw, Ph.D.
20
2
Biocore 323
Fall 2010
E. If the post-synaptic receptor at synapse A is a ligand-gated ion channel that is equally permeable to
Na+ and K+, what will be the reversal potential (ERev) at this synapse?
Janet L. Branchaw, Ph.D.
Biocore 323
Fall 2010
Practice Exam Problems
8. The gene encoding for the nicotinic acetylcholine receptor at the neuromuscular junction has been
cloned and you are studying its function using a frog oocyte heterologous expression system and the
patch clamp technique. This ligand-gated ion channel is permeable to both Na+ and K+ ions. To determine
the relative permeability of each ion, you use the whole-cell recording configuration (shown below),
bathe the cell in saturating doses of nicotine (an agonist), and set the ion concentrations as follows:
[Na+]o = 110 mM
[Na+]i = 10 mM
[K+]o = 7 mM
[K+]i = 160 mM
You clamp the cell at progressively depolarizing voltages and record currents. This is the IV (current –
voltage) plot generated from your data.
I (A)
V (mV)
-100
+100
A. (2 pts) Label the reversal potential on the IV plot.
B. (2 pts) To which ion, Na+ or K+, is the channel more permeable? Explain your answer.
C. (3 pts) Superimpose the IV graph you would generate if you washed out the nicotine from the
bath and recorded currents at these same clamp potentials. (assume there is no acetylcholine
present).
Janet L. Branchaw, Ph.D.
Biocore 323
Fall 2010
11. Botulinum toxin (Botox) blocks chemical synaptic transmission at the neuromuscular junction.
A. Propose a hypothesis to explain Botox’s mechanism of blocking synaptic transmission.
I hypothesize that:
B. Design one simple experiment to test your hypothesis. Be brief, yet complete in your description
of the experiment. (Use only the space provided on this page.) List all possible experimental
outcomes and identify the one(s) that would support your hypothesis.
Exam Problems
9. (3 pts) The neurotransmitter GABA activates GABAA receptors, which are ligand-gated Cl- channels. If
the resting potential in a post-synaptic cell is - 80mV, ECl= -68 mV, and threshold potential is -60mV, is
GABA acting as an inhibitory or excitatory neurotransmitter at this synapse?
Explain your answer in 1 or 2 sentences.
In which direction will the next flux of Cl- across the membrane be to produce the post-synaptic
potential at this synapse?
a. the net flux of Cl- will be into the cell
b. the net flux of Cl- will be out of the cell
c. there will be no net flux of Cl-
11. (17 pts) Release of neurotransmitter at the axon terminal depends on Ca2+ influx through voltagegated Ca2+ channels.
A. (2 pts) Ca2+ acts as a second messenger in most cells. Therefore, intracellular concentrations are
maintained at very low levels. Given that [Ca2+]o= 10-6M and [Ca2+]i= 10-9M in a typical neuron,
calculate the equilibrium potential for Ca2+ (ECa). Show your work.
B. (4 pts) Circle the correct answers in these statements about Ca2+ flux across the axonal
membrane.
a. When Em = +100 mV, the concentration gradient for Ca2+ is [inward / outward] and the
electrical gradient for Ca2+ is [inward / outward].
b. When Em = +100 mV, the [electrical / concentration] gradient will be larger in magnitude.
Therefore, the net current will be [inward / outward].
C. (5 pts) Voltage-gated Ca2+ channels, like voltage-gated Na+ and K+ channels, transition from the
closed to open state when Em depolarizes from rest. Given the conductance, calculate and plot the
peak Ca2+ current at each voltage. Label the axes and the Ca2+ equilibrium potential, ECa.
Janet L. Branchaw, Ph.D.
Biocore 323
Fall 2010
Vm (mV)
-90
-60
-30
0
30
60
90
120
g (S)
0
3
10
17
26
32
35
35
Ipeak (A)
D. (1 pt) What type of experiment would you do to determine the current-voltage (IV) relationship
of a voltage-gated ion channel?
a. current clamp
b. voltage clamp
c. conductance clamp
E. (5 pts) If the [Ca2+]o was experimentally reduced to 10-9M (assume [Ca2+]i does not change), how
would the IV plot in part C change? Show your answer by drawing a second dashed line on the
axis above.
Janet L. Branchaw, Ph.D.
Biocore 323
Fall 2010
Janet L. Branchaw, Ph.D.