Circuits and Computational Neuroscience

Neurosci 613 Fall 2016

Computer Lab 1
Due: Tuesday, November 22 by 5pm
1. In numerical simulations of the Hodgkin-Huxley equations, investigate the voltage and current
thresholds for action potential generation. Begin your simulations with the neuron at resting
potential, then at time=100 ms, apply current pulses of varying amplitudes that last until t=1100
ms. Determine values for your answers to at least 2 decimal places and provide example voltage
time trace plots.
a. The rheobase is the minimal current of infinite duration that results in at least one action
potential. What is the rheobase current for the H-H model (where we are assuming that
1s is infinite duration for the neuron)?
b. As the applied current level is increased from rheobase, several action potentials may be
fired but membrane potential will eventually equilibrate and remain steady at a level
above resting potential by the end of the current pulse. Find the maximum steady state
voltage level that the model neuron can maintain at the end of a current pulse which does
not induce continuous repetitive firing of action potentials. What is the applied current
value to reach that voltage?
c. What is the minimum applied current value that induces continuous repetitive firing of
action potentials to the end of the current pulse?
d. Summarize your results on the voltage and current thresholds for action potential
generation in the H-H model.
2. Numerically compute the frequency-current relation (f-I curve) for the Hodgkin-Huxley model.
Begin your simulations with the neuron at rest and at time t=100 ms, apply 1000 ms long current
pulses of varying amplitudes to generate repetitively firing action potentials. For each of the
below, provide example voltage time trace plots.
a. For applied current density levels up to 60 A/cm2, determine the frequency of the
repetitive action potentials and plot the frequency in Hz versus the applied current
density. Obtain an accurate measurement of frequency based on the interspike interval at
a sufficiently large number of applied current values so that the f-I curve is smooth.
b. What happens to the action potential firing for applied current densities above 60
A/cm2?
c. At what applied current density does the phenomenon known as depolarization block
(when the membrane is too depolarized to support any sustained spiking or oscillatory
activity) occur?
d. Based on your knowledge of how actual neurons respond to increasing levels of
stimulation, discuss limitations of the H-H model in replicating neuron firing and any
constraints on its use to ensure the model accurately reflects the behavior of real neurons.
3. Design and implement a numerical experiment to illustrate that in the Hodgkin-Huxley model the
generation of subsequent action potentials is somewhat inhibited during the
afterhyperpolarization following an initial action potential, known as the relative refractory
period. Provide justification for your experiment and voltage time trace plots depicting your
numerical implementation.

4. Consider the leaky integrate-and-fire (LIF) model: = ( ) + with EL = -65

mV, Vth = -55 mV, Vreset = -70mV, cM = 1 F/cm2, and gL = 0.01 mS/cm2.
a. Numerically determine the current and voltage thresholds for firing up to 2 decimal
places as you did in #1a-c. Provide example voltage time trace plots.
b. Numerically compute and plot the f-I curve of the LIF model for Iapp values between 0
and 2 /cm2 as you did in #2a-c.
c. The H-H and LIF models are very different, however an important difference in the
electrophysiology replicated in H-H and LIF model neurons is that LIF neurons display
characteristics of an integrator while H-H neurons display characteristics of a
resonator. Discuss the evidence for this difference displayed in your results or conduct
additional numerical experiments that illustrate this difference.
5. Challenge problem: The Hodgkin-Huxley model can be switched from a resonator to an
integrator by shifting the activation of the K+ delayed rectifier current to depolarized levels. In
the matlab code hh.m, this is achieved by changing the following parameter values in the
functions alphan and betan: anv = 34 and bnv = 44.
a. Make a prediction about what depolarizing the activation of the K+ delayed rectifier
current will do to the current threshold for firing and the f-I curve.
b. Repeat #1a-c and #2a-c with this version of the H-H model to see if your prediction is
correct.
c. Determine the resonant frequency of the standard H-H model by inputting a subthreshold,
sinusoidally varying applied current to the neuron and identifying the frequencies that
elicit the greatest responses.