Many faculty teaching in psychology, physiology, and medical school courses find that they have only one lecture in which to convey to students the nature of that miniature, propagating electrical explosion - the action potential. Typically a second lecture is devoted to synaptic transmission. Then the course material moves quickly on from these rather difficult topics to subjects such as memory or aggression, to which a student can more quickly relate. Faced with the problem of making the action and synaptic potentials more exciting, so to speak, we designed NIA minimovies for our colleagues to introduce into their PowerPoint lectures. In NIA2 we have attempted to make the minimovies still more lively by linking the voltage to sound.

Figure 3. Lists of minimovies in the Action Potential and Axons categories. Minimovies of aspects of excitatory and inhibitory transmission are also available. The instructor can preview each minimovie before importing it into PowerPoint.

The minimovies (available since NIA1.5) are Quicktime movie files captured by the authors from NIA simulations. They are grouped into three categories: (1) the basic properties of the action potential in a patch, (2) the action potential as it propagates along unmyelinated, myelinated, or partially demyelinated nerve (Fig 3), and (3) the salient features of excitatory and inhibitory postsynaptic potentials. Action potential minimovies demonstrate topics ranging from increasing the stimulus amplitude to the effect of cooling. In NIA2, each voltage trace in the first group is also converted to frequency for an accompanying sound track.

Beyond making lectures more engaging, the use of such movies dispels the inaccurate notions of the propagation of neuronal signals that seem to be difficult to eliminate from textbook material. For example, when students see that the action potential actually spreads out in myelinated nerve, its peak covering many nodes at once, they are usually at first bewildered, for did the text not say that it "jumped" from node to node? Soon the student has the correct notion of the breadth of the voltage change in centimeters as it propagates actively along an axon.

One particularly popular minimovie with our colleagues, derived from the Partial Demyelination tutorial, compares an action potential in unmyelinated and myelinated axon by showing the action potential as it travels along a bare length of axon and then invades a myelinated portion (Fig 4).

Figure 4. Arrested minimovie of the propagation of an action potential in a partially demyelinated nerve of 10 μm diameter. The upper, voltage-versus-space graph diagrams the axon as bare on the left half, with a red recording electrode in the center of the bare portion, and myelinated on the right half (5 nodes and 5 internodes each 1000 μm long), with a blue recording electrode in the first node and a black recording electrode in the last node. The movie was stopped when the peak of the action potential, triggered at the left end, was just about to invade the myelinated half, the depolarization spreading far in front of the impulse. The lower, voltage-versus-time graph shows the complete action potential, since it has passed the red electrode, and the arrested depolarization at the blue and black electrodes.

At first, students find it almost shocking to see the change in the action potential from a rather narrow event in space, its entire overshoot extending over less than 0.5 mm in the bare axon, to a voltage change that remains at peak amplitude over the whole 5 mm of myelinated axon in the simulation! As the action potential traveling in the bare axon approaches the myelinated portion, the depolarization spreading far in front of itself makes absolutely clear how propagation occurs. A separate minimovie of only myelinated nerve shows a stretch that is long enough so the student can see the tiny bumps and dips on the voltage trace at the nodes as the ionic currents surge in on the rising phase and out on the falling phase (Fig 5). Such detail captivates students, in our experience, surprising them and helping them to form a correct picture of what happens to the currents and the voltage at the nodes and internodes. A voltage-versus-time graph associated with this movie that plots the action potential as it passes two locations in the axon is useful in showing medical students, in particular, how conduction velocity is calculated, an essential technique in neurology.

Figure 5. Arrested minimovie of an action potential in a myelinated nerve recorded by electrodes at node 1 and node 9 of 10 nodes 1000 μm apart. The movie has been stopped when the peak of the action potential is at the 6000 μm node. The upper, voltage-versus-time graph shows a complete trace recorded by the red electrode at node 1 and the beginning of the depolarization as the impulse approaches the black electrode at node 9. The lower, voltage-versus-space graph shows the electrode positions. The action potential was started at the left end of the axon.

Students often become engaged when NIA simulations are used interactively at the podium. Running simulations during the lecture is relatively easy, since toggling between PowerPoint slides and a simulation is straightforward on either a PC or a Mac. The effective strategy is to ask the students, for example, "What do you expect will happen to the peak of this action potential if I increase the external sodium concentration? How many of you vote that it will get bigger? How many vote for smaller? How many aren't sure?" A little practice might be necessary before the lecture, but even in a class of over one hundred students this method can work, providing a degree of suspense that is uncommon in standard lectures and causing even the tuned-out students to be curious about the outcome.

A popular NIA tutorial to use in this fashion is, again, Partial Demyelination, but this time stimulated at the myelinated end. When the action potential is triggered at the far right end of the myelinated portion, it propagates normally along the myelinated half but then falters at the junction between the myelinated and demyelinated halves. Hesitating, it ultimately fails to invade the bare axon. Since this condition mimics that of multiple sclerosis, it never fails to intrigue students.

The instructor might now ask, "What bare axon parameters can we change to make this action potential invade and propagate in the bare axon? If we were to set out to look for a drug to help this multiple sclerosis patient, what would we want our drug to do?" Ultimately the class can suggest a drug that partially blocks potassium channels; one that increases the density of the sodium channels in the membrane might be suggested at first but, after discussion, the students might conclude that such a drug would be difficult to design from a biological standpoint. But either a decrease in the potassium channel density or an increase in the sodium channel density in the simulation will lead to invasion of the bare axon and reinforce the students' understanding of threshold as a tug-of-war between the sodium and potassium currents. What about a change in diameter (which tests the students' understanding of capacitance as membrane area)? What about an overdose of the potassium channel blocker, a complete block (which tests their knowledge of the mechanism of the action potential)? Would this overdose kill the patient? (Yes.)

Would a change in temperature facilitate invasion of the bare axon? Multiple sclerosis patients are known to prefer certain temperatures ( Humm et al. 2004 ), but, based on neurophysiology, can the students predict whether the patient might prefer to be cool or warm? Changing the temperature in this tutorial is among the most suspenseful and effective of all of the interactive simulations, probably because of its immediate relation to the disease and perhaps, also, because the temperature change required to permit propagation into the bare axon is so small. When the correct change is made, the action potential hesitates for an excruciatingly long time, finally becoming regenerative and even leading to student applause in our experience! The final answer seems at first counterintuitive but effectively solidifies a student's understanding that channel transitions underlie the action potential and these transitions -- from closed to open to inactivated states -- obey Michalis-Menten kinetics and temperature sensitivity.

Within NIA, essentially any tutorial can be used to engage student interest through suspense. In the Chattering Ion Channels tutorial, the single channel simulations, the lecturer can specify the type of channel in the patch and its number (Fig 6). When there is a single channel, each delivery of the depolarizing pulse leads to a different result because channel opening is stochastic. Ergo the suspense: is there an opening? Does the direction of the current tell us which channel it is? When is the opening -- early or late in the pulse? One opening, or two, or maybe more? Would so many openings be expected of this type of channel? We also find suspense when incrementally increasing the channel number in the patch from one to two, then three, then, ultimately, to hundreds, thousands, and tens of thousands to reveal how macroscopic currents are built up. The "What If? approach" in lecture leads to understanding through engaging curiosity about the outcome.

Fig 6. The results of one run of a voltage step from -65 mV to -15 mV and back (see the Stimulus control panel) in the Chattering Ion Channels tutorial. The patch in this simulation contains one Na channel and one K channel, as specified in the Patch Parameters menu. Clearly the Na channel has opened once and either closed or inactivated; the K channel has opened and closed twice, the second closing happening after the voltage step is over, leading to a smaller outward current through the channel after the step.

If NIA has been introduced in lecture and used interactively, it is relatively easy to make the transition to asking the students to do whole or abbreviated tutorials on their own or in groups in a computer lab. When the time is short, we and our colleagues have found it useful to bypass the tutorials and instead hand out a limited exercise with a set of steps to follow and questions to answer at each step (and then hand in). The instructor circulates through the groups to solve any problems with the running of the simulations, to ask questions to make sure the students are understanding what they are seeing, or to ask what other parameter changes they might make in order to test the hypothesis. "So what experiment could you do here to test if your explanation is correct?" the instructor might say, holding back on giving away answers.

A number of colleagues use NIA in undergraduate neuroscience courses. One colleague used NIA1.5 for two weeks in the laboratory portion of an upper level introductory neuroscience course at Bowdoin College in Maine, USA. Each student had access to NIA1.5 in a computer lab. In the first week, the instructor led the students through several tutorials that were chosen to complement what they learned in lecture. These sessions also gave the students a chance to become facile with the program. In an innovative twist during the second week, the students, working in groups of two, designed their own hypotheses to test. The faculty member and a laboratory instructor met with each group to decide which tutorial provided the ideal parameters to manipulate and therefore was the most appropriate for running their own experiment. One hypothesis, for example, was that unmyelinated axons would be affected at lower concentrations of tetrodotoxin than myelinated axons; the students decreased the Na channel density in equal proportions in the two axon types and measured action potential rate of rise, amplitude, and conduction velocity to come to their conclusions.

Colleagues who have undergraduates do the NIA tutorials in a computer lab setting usually have made individualized materials to complement the tutorials: for example, handouts with specific exercises to be done in each tutorial (separate from those in the published tutorials), questions about the results of simulations, problem sets, and homework. Colleagues have sent us such materials for NIA1 for posting on the NIA website ( http://neuronsinaction.com ). With the publication of NIA2 and the increasing familiarity of faculty with forums on websites, this site provides a potential mechanism for sharing novel ideas about how to use these simulations and tutorials in teaching at any level.

An example of a course using NIA in conjunction with a wet lab is a course in "Principles of Neurophysiology" taught through the Department of Neurobiology and Behavior at Cornell University (Ithaca, NY, USA). The purpose of this upper level, undergraduate course is to introduce students to the power of neural computation as a tool in the laboratory as well as providing a sophisticated laboratory experience in neurophysiology. To this end, the NIA tutorials are integrated with wet lab experiments designed primarily around the Crawdad software package. Although in previous years a textbook had been used for this course, NIA is now the only text; the students refresh and deepen their understanding of neurophysiological concepts through NIA's hyperlinked materials.

The students begin with an RC circuit in the lab and the Membrane Tutorial from NIA. From then on, the tutorials are selected to complement the wet lab preparations rather than being followed in their own order. For example, the next wet lab technique to be learned is extracellular recording; here the Unmyelinated Axon and/or Myelinated Axon tutorials from NIA are useful where conduction velocity can be measured by inserting two virtual electrodes into an axon. As the wet lab moves on to intracellular recording from crayfish muscle fibers and then snail neurons, the NIA tutorials dealing with equilibrium and resting potentials, action potentials and threshold, excitatory and inhibitory synaptic potentials, and then voltage clamp, are introduced as appropriate.

For the midterm and final "exams" in this course, the students must execute a project of their own design that blends the wet and virtual lab experiences and then write it up. In one example of such a project, students recorded the extracellular action potentials from all six axons in the third motor nerve of the crayfish, calculated the six conduction velocities from these recordings, and then estimated their diameter through simulations using NIA. In another project, students recorded action potentials and ionic currents from snail neuronal somata, added potassium channel blockers at increasing concentrations, recorded the changes in amplitude and duration of the action potential and amplitude of the potassium currents, and then simulated these results with the Action Potential and Voltage Clamp tutorials. The students had to design the projects themselves, including figuring out which simulations were appropriate. The instructor finds these "exams" to be an especially rewarding aspect of the course as students truly understand the value of using simulations to illuminate real experiments.