Friday, April 29, 2011

Bursting

Last week in this blog I talked briefly about bursting in pancreatic beta cells. A bursting cell fires several action potential spikes consecutively, followed by an extended quiescent period, followed again by another burst of action potentials, and so on. One of the first and best-known models for bursting was developed by James Hindmarsh and Malcolm Rose (A Model of Neuronal Bursting Using Three Coupled First Order Differential Equations, Proc. Roy. Society Lond, B, Volume 221, Pages 87-102, 1984). Their analysis was an extension of the FitzHugh-Nagumo model, with an additional variable governed by a very slow time constant. Their system of equations is

dx/dt = y – x3 + 3 x2 – z + I

dy/dt = 1 – 5 x2 – y

dz/dt = 0.001 [ 4(x + 1.6) – z]

where x is the membrane potential (appropriately made dimensionless), y is a recovery variable (like a sodium channel inactivation gate), z is the slow bursting variable, and I is an external stimulus current. For some values of I, this model predicts bursting behavior.

There is an entire book dedicated to this topic: Bursting--The Genesis of Rhythm in the Nervous System, by Stephen Coombes and Paul Bressloff (World Sci. Pub. Co., 2005). The first chapter, co-written by Hindmarsh, provides a little of the history behind the Hindmarsh-Rose model:
“The collaboration that led to the Hindmarsh-Rose model began in 1979 shortly after Malcolm Rose joined Cardiff University. The particular project was to model the synchronization of firing of two snail neurons in a relatively simple way that did not use the full Hodgkin-Huxley equations... A natural choice at the time was to use equations of the FitzHugh [type]….

A problem with this choice was that these equations do not provide a very realistic description of the rapid firing of the neuron compared to the relatively long interval between firing. Attempts were made to achieve a more realistic description by making the time constants … voltage dependent. In particular so the rates of change of x and y were much smaller in the subthreshold or recovery phase. These were not convincing and it was not until Malcolm raised the question about whether the FitzHugh equations could account for “tail current reversal” that progress was made.

The modification of the FitzHugh equations to account for tail current reversal was crucial for the development of the Hindmarsh-Rose model.”
For those not familiar with the FitzHugh-Nagumo model, see Problem 33 in Chapter 10 of the 4th edition of Intermediate Physics for Medicine and Biology, or see the Scholarpedia article by FitzHugh himself, written before he died in 2007. If you want to see some bursting patterns, check out this youtube video. It is not great, but you will get the drift of what the model predicts.

My Friend Artie Sherman also had a chapter in the bursting book, titled “Beyond Synchronization: Modulatory and Emergent Effects of Coupling in Square-Wave Bursting.” He has been working on bursting in pancreatic beta cells for years, as a member (and now chief) of the Laboratory of Biological Modeling in the Mathematical Research Branch, the National Institute of Diabetes, Digestive and Kidney Diseases, part of the National Institutes of Health. His work is the best I am aware of for modeling bursting.

2 comments:

  1. The July 2011 issue of the Journal of Biological Physics is a special issue about the Dynamics of Neuronal Bursting: http://www.springerlink.com/content/0092-0606/37/3/

    ReplyDelete