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.
  1. 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).
  1. Students will understand the role of the neurotransmitter receptor in determining a neurotransmitter’s effect on the post-synaptic cell.
  1. 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.
  1. Students will be able to design experiments to measure the reversal potential at a synapse.
  1. Students will be able to determine if a molecule is a neurotransmitter based on experimental data about the behavior of that molecule.
  1. 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: 122-137Ch 4: 12-19

Biology: Ch 48: 1056-6148.4: 1, 2, 3; self quiz: 4, 5, 6, 9

The World of the Cell: Ch 13: 380-8813-1, 13-10, 13-11

Reading Questions:

  1. Which type of synapse, electrical or chemical, conducts electrical signals from one cell to the nextmost quickly? Which type of chemical synapse, direct or indirect, is faster?
  1. How are neurotransmitters different from hormones as chemical messengers? How are they different from neuromodulators?
  1. Outline the steps involved in direct chemical synaptic transmission.
  1. Compare direct and indirect chemical synaptic transmission.
  1. Describe the ionic basis underlying excitatory post-synaptic potentials (EPSPs) and inhibitory post-synaptic potentials (IPSPs) produced by direct chemical synaptic transmission.
  1. Why does an increase in both Na+ and K+ conductance in the post-synaptic cell result in depolarization of the membrane potential?
  1. What is a post-synaptic current? How is it related to a post-synaptic potential? (Hint: Consider Ohm’s Law.)
  1. Why is the reversal potential in the post-synaptic cell at a synapse usually not equal to the equilibrium potential for a single ion?
  1. How can the same neurotransmitter produce an EPSP at one synapse and an IPSP at another?
  1. Why are drugs that target neurotransmitter receptors powerful tools in the treatment of nervous system disorders?
  1. 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?
  1. T/FOne end plate potential (EPP) in a skeletal muscle fiber generates one action potential in that fiber.
  1. T/FOne excitatory post-synaptic potential (EPSP) in an-motor neuron cell body generates one action potential in that neuron.
  1. ______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)
  1. ______summation occurs when post-synaptic potentials occur simultaneously at different synapses.The (longer / shorter) the length constant () of the membrane, the fartherpost-synaptic potentials will travel, and the more effective the summation can be. (circle)
  1. 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+).

  1. Experimental Design:

Test experiment –

Control experiment -

  1. 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.

[Na+]o = 150 mM[Na+]i= 15 mM

Ex= 62log[X]o[K+]o = 5 mM[K+]i = 150 mM

z [X]i[Cl-]o = 109 mM[Cl-]i = 8 mM

  1. Calculate the equilibrium potential for each ion.

ENa =EK = ECl =

Janet L. Branchaw, Ph.D.

Biocore 323

Fall 2010

  1. 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.

Janet L. Branchaw, Ph.D.

Biocore 323

Fall 2010

Janet L. Branchaw, Ph.D.

Biocore 323

Fall 2010

  1. 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.
  1. 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.

Janet L. Branchaw, Ph.D.

Biocore 323

Fall 2010

  1. 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?

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 oocyteheterologous 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:

Janet L. Branchaw, Ph.D.

Biocore 323

Fall 2010

[Na+]o = 110 mM[K+]o = 7 mM

[Na+]i = 10 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

  1. (2 pts) Label the reversal potential on the IV plot.
  2. (2 pts) To which ion, Na+ or K+, is the channel more permeable? Explain your answer.
  3. (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.

  1. Propose a hypothesis to explain Botox’s mechanism of blocking synaptic transmission.

I hypothesize that:

  1. 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?

  1. the net flux of Cl- will be into the cell
  2. the net flux of Cl- will be out of the cell
  3. there will be no net flux of Cl-

11. (17 pts) Release of neurotransmitter at the axon terminal depends on Ca2+ influx through voltage-gated Ca2+ channels.

  1. (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.
  1. (4 pts) Circle the correct answers in these statements about Ca2+ flux across the axonal membrane.
  2. When Em = +100 mV, the concentration gradient for Ca2+ is [inward / outward] and the electrical gradientfor Ca2+ is [inward / outward].
  3. When Em = +100 mV, the [electrical / concentration] gradient will be larger in magnitude. Therefore, the net current will be [inward / outward].
  1. (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) / g (S) / Ipeak (A)
-90 / 0
-60 / 3
-30 / 10
0 / 17
30 / 26
60 / 32
90 / 35
120 / 35

Janet L. Branchaw, Ph.D.

Biocore 323

Fall 2010

  1. (1 pt) What type of experiment would you do to determine the current-voltage (IV) relationship of a voltage-gated ion channel?

a. current clampb. voltage clampc. conductance clamp

  1. (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.