Neurons: Cellular and
Network Properties

LECTURE OUTLINE (CHAPTER 8)

LECTURE OBJECTIVES

1. Describe the functions of the glia and neurons in the nervous system.
2. Briefly review of membrane potential.
3. Introduce basic concepts, such as hyperpolarization/depolarization, graded potentials/action potentials, etc.
4. Explain how a resting membrane potential can transform into a nerve impulse.
5. Explain how selective ion gating generates the action potential.
6. Explain the principles behind saltatory conduction of an action potential
7. Describe how a nerve impulse passes from neuron to neuron.
8. Establish how neurotransmitters and neuropeptides act at receptors on the post-synaptic membrane.
9. Discuss how the interplay of inhibitory and stimulatory inputs determines if a post-synaptic neuron fires.
10. Explain and evaluate the types of intercellular communication that exist.

LECTURE OUTLINE

I. CELL TYPES OF THE NERVOUS SYSTEM

   A. Neurons communicate information
   B. Glia support or service the central nervous system and its neurons
     1. Astrocytes
     2. Oligodendrocytes
     3. Microglia
     4. Ependymal cells   

II. REVIEW MEMBRANE POTENTIAL
  
     A. Biophysical properties determine ion distribution 
          1. Na+ outside, K+ inside, Anion- inside
          2. Resting membrane is negative inside--positive outside
          3. Passive ion flow is much more important than the Na+/K+ ATPase pump
     B. Changes in ion permeability alters membrane potential
          1. Goldman equation (=GHK equation) revisited
          2. Change in the permeability for a number of ions affects 
              resting potential
     
III. CHANGES IN MEMBRANE POTENTIAL

    A. Graded Potentials
         1. Hyperpolarizing stimulus verses depolarizing stimulus
         2. Stimulus strength
         3. No refractory period
         4. Local (=passive) current spread
              a. Local current deteriorates with distance
    B. Action Potential (=nerve impulse)
         1. Characteristics of the Action Potential (AP)
             a. At threshold, firing is all-or-none
             b. Refractory period present
             c. Local current spread 

IV. ACTION POTENTIAL: ELECTRICAL CHARACTERISTICS

    A. Selective Na+ conductance followed by selective K+ conductance 
         1. Positive feedback for Na+     
         2. Voltage change affects ion gating (=voltage-dependent gates)
         3. Roles of Na+ and K+ flux in the action potential (Animation)
              a. Only very small numbers of ions are involved
         4. Role of the Na+/K+ ATPase pump at re-establishing ion gradients  
    B. Refractory period
         1. Significance of the refractory period
              a. Absolute refractory period
              b. Relative refractory period
    C. Movement of the AP along the axon
         1. Why does the AP start at the axon hillock?
         2. AP propogation down the axon
    D. Saltatory Conduction
         1. The myelin sheath (Schwann cell) and the nodes
         2. Passive current spread (Animation)
               a. Multiple Sclerosis (MS)
         3. Axon diameter also influences speed of conduction 
              
V. SYNAPSES

    A. Electrical Synapse 
         1. Structure of the gap junction
         2. Electrical properties
    B. Chemical Synapse: Acetylcholine as an example
          1. General structure of the chemical synapse
          2. Ach synthesis and packaging of release
          3. Vesicle docking and exocytosis
          4. Summary (Animation)  
    C. General neurotransmitter actions on the post-synaptic membrane
         1. Comparison of slow and fast changes in neurotransmitter action 
         2. Example of a fast change:  The post-synaptic membrane of skeletal muscle        
               a. Ach excites the nicotinic receptor which opens a Na+/K+ channel
               b. Depolarization of the post-synaptic membrane occurs
    D. The fates of secreted neurotransmitter
         1. SSRIs are drugs that alter Serotonin efficacy (e.g., Zoloft) 
 *    
VI. INTEGRATION OF POSTSYNAPTIC POTENTIALS (EPSP/IPSP)

     A. Excititory and inhibitory synapses  
     B. How integration of multiple inputs is achieved.
          1. Postsynaptic response
               a. Spatial and temporal summation (See also: Figs. 8-27 and 8-28)
               b. Cancellation of a EPSP by a IPSP	
          2. Presynaptic inhibition and facilitation  
     C. Convergence and divergence in neuronal pathways
     D. Summary: Physiology of the synapse

VII. NEUROTRANSMITTERS AND NEUROPEPTIDES

    A. "Classical" Neurotransmitters
    B. Two important points about neurotransmitters
         1. Action of multiple neurotransmitters permits homeostatic
            processing
         2. The effect of a neurotransmitter (=messenger) is always 
             specific for a target tissue
              a. Example: Ach generates different responses in target cells
    C. Neuropeptides are neuromodulators
         1. Some characteristics of neuropeptides

Reading assignment: Please read Chapter 9 for the next lecture.

STUDY QUESTIONS ON NEURONS (Chapter 8)

BASIC FACTS AND TERMS

Compare and contrast the functional characteristics of a graded response (e.g., post-synaptic potential) and an all-or-none response (e.g., action potential) See Table 8-3 in Silverthorn.
Compare and contrast the functional charactersitics of an electrical synapse and a chemical synapse.
List the possible fates of neurotransmitter once it is released into the synaptic cleft?
Read about multiple sclerosis (MS) in the text. What is the neural basis for this disease?
Here is a general question on secretion of neurotransmitters. In an outline or a diagram, trace the course of 1) synaptic vesicle formation, 2) vesicle loading with neurotransmitter, 3) vesicle transport to the terminal, and finally 4) vesicle secretion at the synapse. List specific protein(s) involved at each step and explain how they might function. Perhaps this figure will help.
What is an EPSP and an IPSP? What effect does each have on the probability that post-synaptic neuron will fire? How are graded potentials involved in this process?
Read about Parkinson's Disease in the text. What treatments slow the progress of this disease and how do they work at the cellular level? What are stem cells and how might they be used in fighting this disease?
Define and give the physiological significance (how or why it is physiologically important) for the following terms:
- Competitive and noncompetitive (=allosteric) binding
CONCEPTS
Describe the permeability changes and ionic fluxes that occur during the action potential (AP). What factors affect the timing of ion conductance during the AP (e.g., What opens an ion gate or closes it)?
Outline the process of neurotransmitter release into a synapse. Start with the arriving action potential and end with neurotransmitter release. See Fig. 8-21.
Following an action potential spike, the neuron briefly becomes more hyperpolarized (that is, more negative than -70 mV). What is the electrochemical basis for this hyperpolarization? Which process returns the membrane potential to -70 mV eventually?
What is local (=passive) current flow along the length of the neuron and how it is important to neuronal function? Why does passive current flow diminish farther from the stimulus source?
During the action potential, what are the forces that cause K+ to leave the neuron so rapidly, resulting in a hyperpolarized membrane (> -70mV)?
When a neurotransmitter is said to be "excitatory", what does that mean with regard to: 1) post-synaptic potential, 2) ion flux at the post-synaptic membrane, and 3) the probability that the post-synaptic neuron will fire.
How are synaptic vesicles transported to the terminal, and how are they loaded with neurotransmitter at the terminal?
Contrast 1) temporal and 2) spatial summation of a post-synaptic potential (PSP). See Fig. 8-28.
Compare contiguous conduction and saltatory conduction.
How does a neurotransmitter, such as Ach or NE, act at the membrane of a post-synaptic membrane? Explain.
Distinguish between presynaptic inhibition and an inhibitory post-synaptic potential (IPSP). See Fig. 8-29.
Using the following diagram of an action potential, describe what happens with regard to Na+ flux, K+ flux, and the Na+/K+ ATPase pump at a, b, c, d, and e. When are the Na+ gates open and when are they closed? K+ gates?

REASONING AND PROBLEM SOLVING
EDTA is a chemical that tightly binds all Ca++. When a pre-synaptic nerve is stimulated in the presence of EDTA, the pre-synaptic cell fires an action potential, but the post-synaptic neuron does not. If you remove the EDTA, both the pre- and post-synaptic nerves fire action potentials. Explain these results, given your knowledge of how Ca++ is involved in communication between neurons.
The only thing stated about Cl- is that this ion is in high concentration in the ECF around the neuron. But some neurons have Cl- gates in the plasma membrane. Can you think of a mechanism by which Cl- would hyperpolarize membrane potential? Explain your answer. So, in general, what do you have to do hyperpolarize a membrane potential?
Why is regulation of blood K+ so important for normal nerve/muscle function. What happens to nerve function when blood K+ is too high? too low?
Schizophrenia is believed to be caused by excessive activity of the neurotransmitter, dopamine, in a particular region of the brain. Explain why symptoms of schizophrenia sometimes occur as a side effect in patients being treated for Parkinson's disease (e.g., the adminstration of L-DOPA).
Curare (=a dart gun poison from Africa) is a drug that causes paralysis of skeletal muscle. The drug acts at the synapse between the nerve and the muscle cell. Acetylcholine is the neurotransmitter at this synapse. First, what are some of the ways curare might act at the neuromuscular junction to cause paralysis? Second, pick one of these possibilities and describe how you might test if it acts in this manner.
If you electricially stimulated the middle of an axon to elicit an action potential, would the action potential travel in one or both directions from the point of stimulation? Explain why? How far along the axon would the action potential go? Why?
For the pharmacuetical industry the perfect drug is one that has a specific action to treat disease, but with minimal side effects. A major thrust in this research effort examines drugs which affect neurotransmitter efficiacy (e.g., synthesis, release, breakdown, or action at the receptor). For example, a disease might result from excessive secretion of neurotransmitter. Given your knowledge of neurotransmitter physiology, can you list several different approaches that a researcher could use to develop drugs to lower neurotransmitter level? What experimental approaches are available to treat disease resulting from inadequate levels of neurotransmitter?
The diagnosis of a recently discovered medical condition is that the serotonin level in a particular brain pathway is very low (that is, the serotonergic neurons are releasing insufficient amounts of the neurotransmitter, serotonin). The National Institutes of Health asks you to develop a line of research aimed at alleviating this condition. Given you knowledge of how neurotransmitters work, outline a couple of different approaches that you might use to treat this problem. Use correct physiological terminology.
Use this Action Potential Simulator to answer the following questions. This stimulator assumes slightly different values for Na+ and K+ than are given in the text. So use the following values to answer the questions:
Question. If you added a little K+ to the outside of the nerve, how would that alter the action potential and why? Hint: First calculate the Equilibrium potential for K+ (E K+) with slightly more K+ outside. Then set the E K+ in the Simulator to that value and hit [Start]. How did the resting membrane potential change (no change, closer to 0, farther from 0)? What effect did this adjustment have on K+ conductance? Can you explain why these changes occurred?
Question. What happens if you lower K+ on the outside of the membrane? Do changes in outside Na+ have this magnitude of an effect?

Last revised: January 31, 2008

Neurons: Cellular andNetwork Properties

Neurons: Cellular and
Network Properties