Spaced out Neurons

A grant to develop software tools to analyze how neurons distribute themselves within the brain

Do neurons need personal space like people in an elevator? Are they influenced by their neighbors or do they randomly find a home in the brain? If the arrangement is patterned, what is the cause of the pattern?


These are all unanswered questions in developmental neurobiology, but that may soon change as a result of a National Institute of Mental Health grant to a group of multi-disciplinary researchers at the University of California, Santa Barbara and the University of Cambridge.


“We’re creating software tools to analyze how neurons distribute themselves within the brain,” says Benjamin Reese, PhD, principal investigator on the grant and a professor of psychology at UCSB. “We understand how neurons are born, the instructions governing their fate and how they then migrate, but virtually nothing about how they distribute themselves in three-dimensional space.”


Reese and his colleagues have found that many types of neurons in the retina (essentially a two-dimensional space) respect one rule: they avoid being positioned near one another. This rule results in neurons being spread evenly across the retina, providing a uniform sampling of the visual scene—a characteristic required for good eyesight.


Measuring the geometrical relationships defined by the position of neurons in 3-D, as shown on the right, is far more computationally demanding than doing so for the 2-D version on the left.But neurons in other parts of the brain might function under additional or completely different rules. Moreover, 3-D space is harder to model using current software. “The algorithms we’ve created for studying the distribution of cells in two dimensions are all Matlab-based scripts,” Reese says. “Once we add the depth dimension, they become extremely cumbersome.” So he and his colleagues, including co-principal investigator Steven Eglen, DPhil, a lecturer at the University of Cambridge, are re-writing portions of the scripts in a lower-level language to improve computational efficiency.


The software will both simulate neuronal populations and compare the simulations to real biological data. The first simulation step: throw virtual cells into a defined space with various constraints (e.g., a specified vicinity to similar, or other types of, cells) until the cells achieve the same density as is found within a region in the brain. The researchers will also generate experimental data using transgenic animals that express fluorescently marked populations of nerve cells. They will measure those neurons’ x-y-z coordinates and feed them into the software program. The software can then determine the geometry of the simulations repeatedly, looking for the best fit to the real biological data.


The group plans to make the software available to the public. “By July of 2006, we expect to have a website up and running with both two and three dimensional software available for others to download and use,” says Reese.


Eventually, Reese would like to understand both cell spacing and its causes: “Is what spaces them apart a diffusible factor emitted by the cells, or is it contact-based, mediated by outgrowing dendrites?” Reese asks.


The understanding of neuron spacing may enlighten us about developmental disorders of the brain, Reese says. Mutations in genes that influence neuronal spacing may, in turn, alter the synaptic connectivity and circuit formation within the nervous system, altering brain function.


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