Modeling Neuron Firing by Transitions in a Double-Well Potential

Tiany Kolba
Duke University Mathematical Biology Workshop

May 16, 2011

Neuron

Voltage Across Cell Membrane

Electrical signal results from a change in the voltage across the cell membrane of the neuron

Let x (t ) = xi (t ) xe (t ) = the voltage across the cell membrane at time t where xi (t ) = the internal voltage at time t xe (t ) = the external voltage at time t

Key component of understanding neuron ring is to model x (t )

Excitability
Neurons, like most cells, maintain a stable equilibrium voltage across the cell membrane. Two types of cells:
nonexcitable: if a signal is applied to the cell, the voltage returns directly to its equilibrium value after the applied signal is removed excitable: if the applied signal is suciently strong, the voltage goes through a large excursion, called an action potential, before eventually returning to equilibrium

Neurons are examples of excitable cells!

Action Potential

Hodgkin-Huxley Model

Most important model in all of the physiological literature Developed in 1952 by Alan Hodgkin and Andrew Huxley Deduced from experiments on a squid giant axon ( 1 mm in diameter) Models the voltage across the cell membrane, x (t ), through a system of 4 ordinary dierential equations (ODEs)

Hodgkin-Huxley Model
Four functions: x (t ) = voltage across the cell membrane m(t ) = eect of the sodium channels in the cell membrane n(t ) = eect of the potassium channels in the cell membrane h(t ) = eect of all the other ion channels in the cell membrane

Fitz-Hugh Nagumo Model

Simplies the Hodgkin-Huxley Model to a system of 2 ODEs Developed in 1961 Two functions: x (t ) = voltage across the cell membrane y (t ) = a variable which represents the combined eect of the various ion channels

Fitz-Hugh Nagumo Model

dx dt dy dt where a (1, 2) is a parameter which controls the value of the voltage equilibrium << 1 represents the time scale separation
motion of the voltage, x (t ), is fast motion of the ion channels, y (t ), is slow

3 =x1 3x y

= (x + a)

Equilibrium
Equilibrium occurs when dy dx = =0 dt dt

The unique equilibrium point for the Fitz-Hugh Nagumo model is: x y = a 3 = a + 1 3a

Starting from equilibrium in the absence of a stimulus, the neuron would never re according to the Fitz-Hugh Nagumo model. However, sometimes neurons do re even in the absence of a stimulus.

Addition of Noise

Most things in nature, including neurons, do not behave exactly deterministically, but have inherent randomness, or noise. Thus, to have a more realistic model of neuron ring, we add noise to the Fitz-Hugh Nagumo Model: dx 1 dB = x x3 y + dt 3 dt dy = (x + a) dt where > 0 is a parameter which controls the noise strength

Model of Noise
We will let B (t ) be Brownian Motion

What is Brownian Motion? Named after Robert Brown, a Scottish botanist, who in 1827 observed pollen grains executing a continuous jittery motion when suspended in water Most famous example of a stochastic process (i.e., a collection of random variables, indexed by t ) For each xed t 0, B (t ) is a normal random variable with mean 0 and variance t

Graph of Brownian Motion

Fitz-Hugh Nagumo Model with Noise

dx dt dy dt

1 dB = x x3 y + 3 dt = (x + a)

Addition of noise transforms the ordinary dierential equations (ODEs) into what are called stochastic dierential equations (SDEs) Overarching goal of project is to analyze how adding noise to the Fitz-Hugh Nagumo model aects the behavior of x (t ) and neuron ring

Project Outline I

Reduce the Fitz-Hugh Nagumo model to one ODE of the form: dx = W (x ) dt where W (x ) is a double-well potential by observing that since the motion of y (t ) is very slow, y (t ) can be treated as a constant.

Describe how the solution, x (t ), to the above ODE can be interpreted as the motion of a particle moving along the double-well potential, W (x ).

Project Outline II
3

Learn more about Brownian motion and how randomness can be added to ODEs to form SDEs. Simulate the solution to the SDE: dx dB = W (x ) + dt dt using Matlab and observe that the qualitative behavior fundamentally diers from that of the corresponding ODE.

Analyze the factors (such as the shape of W (x ) and the size of ) which aect transitions in a double-well potential and interpret the transitions in the context of neuron ring.

References

R. E. Lee DeVille, Cyrill B. Muratov, and Eric Vanden-Eijnden. Two distinct mechanisms of coherence in randomly perturbed dynamical systems. Physical Review E 72, 031105, 2005. James Keener and James Sneyd. Mathematical Physiology. Springer, 1998. Gregory F. Lawler. Introduction to Stochastic Processes. Chapman and Hall, 1995.