Donald Pfaff - How the Vertebrate Brain Regulates Behavior: Direct from the Lab

When I began in neurobiology, there was a longstanding problem: most scientists felt that it was necessary to work with extremely simple animals to understand how nervous systems govern behavior. Vertebrates and especially mammals were considered to be too hard, too complex. A new paradigm was needed to attack the scientific problems of how the vertebrate brain regulates behavior. To fill that need, I analyzed and then exploited the effects of hormones on behavior. In doing so I reaped the analytic advantages of chemical specificity (steroid hormones) and neuronal specificity (circuitry for a simple mammalian behavior) so as to understand how a biologically important mammalian behavior is regulated.

To put it another way, a neuroscientist might win by studying complex functions in a simple organism or by studying a simple behavior in a complex organism. I chose the latter. Having done so, I succeeded in linking molecular chemistry to physiology and ultimately to the causation of behavior. In recounting my own laboratorys work I am going through all the steps that any laboratory must to solve problems as our science of the vertebrate brain develops.

In the first several chapters of this scientific account, a review of some of my laboratorys accomplishments, I will show that we produced the first demonstrations of specific molecular changes in particular neurons that drive a chain of social behaviors of extraordinary biologic importance. That is, I proved that the females behavioral response to the males mount, which is essential for fertilization (lordosis behavior), is driven by specific estrogen-dependent molecular events in ventromedial hypothalamic neurons, which regulate the neuronal circuit that we subsequently worked out.

As mentioned, the first creative step was to find a problem worth solving that, in fact, would turn out to be solvable: how the chain of behaviors essential for reproduction is organized and regulated. My findings, starting 50 years ago, are related here, together with the work of others who have enlarged the field of neuroendocrinology to the point where it presents the best opportunities for relating molecular genetics to neuroscience and behavior.

Some people think that mechanistic explanations for behavior should be set up against evolutionary explanations. No! I note that my type of workdiscovering brain mechanisms for behaviordoes not contradict those who emphasize how behavioral regulation has evolved, an aspect of biology and medicine led by E. O. Wilson, at Harvard (Wilson 1975). My field of neuroscience is complementary to Wilsons field, including his seminal work on sociobiology. Wilson thinks about how biologically important behaviors have evolved through time, while I have discovered mechanisms that are the result of that evolutionary process and drive behaviors right now. In fact, it is those very mechanisms that we neuroscientists study, which actually evolve!

To put it another way, I figured out how the nervous system works by solving the problem posed by a specific behavioral function. Rather than asking How does the brain work? I worked out how a specific function is accomplished. I had the advantage of working with a hormone-controlled behavior, so I could triangulate brain mechanisms, viewing them from one angle as hormone targets and from another as behavioral response producers. By in this book, you will see that we achieved a realization of these brain mechanisms in physical terms.

I also note that although traditionally neuroscientists considered the central nervous system to be an isolated entity and studied it as such, in the course of my analyses of lordosis behavior mechanisms I was studying a behavior that is necessarily and essentially social.