Control of Neuron Number and Stereology
An Annual Review of Neuroscience article published with Karl Herrup in 1988 that considers the roles of cell proliferation and death on the control of neuron number. The perspective is primarily evolutionary and developmental rather than molecular. How many neurons are there in a human brain? Our updated estimate is an average of about 100 billion, of which 20 billion are neocortical and most others are cerebellar granule cells.
This paper by R. W. Williams and Pasko Rakic (1988) describes a novel method to count cells in sectioned material. Direct three-dimensional counting is related to the optical dissector described in the same year by Gundersen and colleagues. However, the method is actually an adaptation of the counting brick method introduced by Howard and colleagues in 1985. Unlike some variants of the dissector, 3D counting does not require the user to keep track of a sequential set of reference and lookup planes, explicitly or implicitly. Counting rules are simple. This paper has many details on the counting method, specific rules for including and excluding cells, and details on setting up a video microscope with Z-axis encoders and differential interference contrast (DIC) optics. This is a substantial revision with corrections and additions suggested (or motivated) by H. Gundersen, V. Howard, and C. S. von Bartheld. Published in The Journal of Comparative Neurology. Upload the QuickTime movie of a 3D counting box and please forgive the marginal image quality of this first example. You can now also control one of our Zeiss microscopes using the iScope Java applet and view live video.
An annotated copy of M. Abercrombie's classic 1946 paper “Estimation of Nuclear Population from Microtome Sections” published in The Anatomical Record, volume 94. Abercrombie’s entire text with figures is reproduced. In this important technical paper Abercrombie describes two methods to count cells in sectioned material: the well-known but somewhat biased Method 1 and the neglected and entirely unbiased Method 2. Annotations are by R. W. Williams, June 1998.
A study by Drs. Glenn Rosen and Jason Harry provides a series of guidelines for the estimation of brain volume from serial sections. They find that the Cavalieri method provides better approximations under some circumstances. However, this method does require equally-spaced sections. They describe methods for the estimation of brain volume from unequally-spaced sections, including an estimator based on the fitting of piece-wise parabolic curves to sets of data.
Illustration of the Spanish Wildcat
by Michael Rothman from a review article in the New York Times.
An intriguing study that examines the cellular consequences of evolutionary changes in brain size in the cat lineage (big-brained wildcats versus small-brained domestic cats). Published in The Journal of Neuroscience by R. W. Williams, Carmen Cavada, and Fernando Reinoso-Suarez. This HTML edition includes several new figures. This work was reviewed with moderate precision by The New York Times, but was discussed most succinctly in News of the Weird.
This paper, written with Pasko Rakic, summarizes data on the rise and fall of neuron number in the dorsal lateral geniculate nucleus of rhesus monkeys from early in gestation (E48) through to maturity. What is the relationship between cell death in the lateral geniculate nucleus, visual cortex, and retina? One unexpected finding was that the severity of neuron death is extraordinarily high in the future magnocellular part of the LGN. This paper was published in 1988 in The Journal of Comparative Neurology.