Princeton University
Department of Molecular Biology

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Tiger Talks


From Photons to Perception

Wed, Nov 05, 2003
Location - TBA


Professor of Molecular Biology


In the 19th century, the subjects that we now call physics and biology were not separate disciplines. Great figures of classical physics such as Helmholtz, Maxwell and Rayleigh were especially fascinated by the problem of perception: how do we (and other animals) "measure" the properties of the world around us, and how do we make sense out of these measurements? In this talk I will try to give an overview of the century long collaboration between physicists and biologists to understand the nervous system, highlighting some classical results and also trying to give a feeling for the current frontier.

Sample ImageI will focus in particular on two topics within the general theme. First, the remarkable fact that the visual system can detect a single quantum of light (a single photon) when it is absorbed by the receptor cells in the retina. Counting a single photon means that the retina has pushed all the way to the limits of sensitivity allowed by the laws of physics. When a single photon is absorbed, one molecule of rhodopsin - one molecule out of one billion molecules in each receptor cell! - changes its structure, and the receptor cell must have the machinery to detect this individual molecular event. This would be extraordinary even if it were the only example of such behavior, but we will see that sensitivity at the single molecule level occurs in many biological systems, even in bacteria, and that there are some unifying principles from physics that allow us to understand both the limits to performance and the kinds of mechanisms that biological systems must have evolved to achieve this ultimate sensitivity.

A second topic is the fact that once information enters the nervous system from our eyes, ears, and other sense organs it is immediately encoded in an almost digital code made from identical electrical pulses called action potentials or spikes. I'll demonstrate this by having the audience "listen in" on the spikes transmitted along nerve cells in our arm as we flex our muscles. Our understanding of how these spikes are generated is essentially complete: we can write down the mathematical equations that describe how special protein molecules (called ion channels) in the nerve cell membrane react to electric fields to change states and allow the flow of electric current, we understand how the observed spikes emerge from the complicated nonlinear dynamics predicted by these equations, and recently we have even "seen" the structure of these molecules. Much more difficult is the question of what the spikes "mean" to the brain. I'll review work which measures how much information each spike can convey, how special patterns of spikes can convey extra information, how we can read out the coded information, and how the code used by the brain adapts to different situations to optimize the information that the brain can collect. I'll conclude by emphasizing the common questions about codes at many different levels of biological organization, from the genetic code to the neural code to language.

How are spikes generated?

The understanding of how spikes are generated is now an almost classical subject. Some of the great contributors to the subject have been honored by major scientific prizes, and the essays written by the people who give and receive these prizes provide a convenient (if not always complete) guide to the history of the subject, sometimes enlivened with glimpses of personality and the sociology of science.

The British scientists Alan Hodgkin and Andrew Huxley made a major step in a series of papers fifty years ago when they showed how the generation and propagation of spikes in the nerve cells of a squid could be understood in terms of opening and closing of "gates" in the cell membrane. By clever experimental manipulations they were able to isolate the dynamics of each kind of gate, and then write down equations that describe these dynamics; the same equation predict, with no further assumptions, that spikes will be generated and will move along the nerve cell at the speed observed in real cells.

In 1963, Hodgkin and Huxley were awarded the Nobel Prize in Physiology or Medicine; (click here: for the lectures that they gave on the occasion of the prize, as well as short biographies) . Hodgkin gave a brief, engaging and lively account of their collaboration in an essay published in the book The Pursuit of nature: informal essays on the history of physiology (Cambridge University Press, 1977); Huxley also has a chapter in this book, describing his later work on the mechanism of muscle contraction.

The Hodgkin-Huxley model predicts that opening and closing of the "gates" in the nerve cell membrane should be accompanied by very small electrical signals called gating currents. Crucial to the model is that different there are different kinds of molecules in the membrane that selectively allow the passage of current carried by different ions (sodium, potassium, ... ). Because the dynamics of the spike ultimately come from the opening and closing of gates in individual molecules, there is an inevitable randomness as each molecule gates independently; continuous progress in experimental technique made it possible to observe this "channel noise" and ultimately the electrical current flowing through single channel molecules as they open and close.

In 1991, Erwin Neher and Bert Sakmann shared the Nobel Prize in Physiology or Medicine for pioneering experiments observing the current flow through single ion channel molecules; (click here: for the press release that described their contributions, the lectures given by Neher and Sakmann on receiving their prize, and brief biographies. In 1999, the Lasker Award for Basic Medical Research acknowledged a generation of progress in understanding ion channels: Clay Armstrong was cited for his work on channel gating, Bertil Hille for his contributions to understanding the selectivity of channels, and Rod MacKinnon for revealing the structure of the potassium channel through X-ray diffraction. The Lasker Award web site includes a beautiful essay by Denis Baylor explaining the development of the field, as well as the press release announcing the award and information about the individual prize winners , including interviews. MacKinnon also went on to share the 2003 Nobel Prize in Chemistry; and eventually his lecture will appear there as well.

The Pulfrich Effect

As I'll explain in the lecture, ideas about adaptation and coding come together in a simple illusion called the Pulfrich effect. I probably won't have time to demonstrate this illusion, however, so you might try it at home. This is a web site with a good guide to such demonstrations and which includes both a "high tech" version (you can have people look at a java applet on the computer screen) as well as references to the Amateur Scientist low tech versions. Here is a bare bones summary website.

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