Building a Brain--One Neuron at a Time

Neuroscientists do not really understand individual neurons very well. They are only now just learning how to culture and study neurons at low density, without contaminating them with serum or blood plasma.

First, the researchers scaled down the size of the fluid-filled chambers used to hold the cells. Chemistry graduate student Matthew Stewart made the small chambers out of a molded gel of polydimethylsiloxane (PDMS). The reduced chamber size also reduced – by several orders of magnitude – the amount of fluid around the cells, said Biotechnology Center director Jonathan Sweedler, an author on the study. This “miniaturization of experimental architectures” will make it easier to identify and measure the substances released by the cells, because these “releasates” are less dilute.

...Second, the researchers increased the purity of the material used to form the chambers. Cell and developmental biology graduate student Larry Millet exposed the PDMS to a series of chemical baths to extract impurities that were killing the cells.

Millet also developed a method for gradually perfusing the neurons with serum-free media, a technique that resupplies depleted nutrients and removes cellular waste products. The perfusion technique also allows the researchers to collect and analyze other cellular secretions – a key to identifying the biochemical contributions of individual cells.


... This combination of techniques enabled the research team to grow postnatal primary hippocampal neurons from rats for up to 11 days at extremely low densities. Prior to this work, cultured neurons in closed-channel devices made of untreated, native PDMS remained viable for two days at best.

The cultured neurons also developed more axons and dendrites, the neural tendrils that communicate with other cells, than those grown at low densities with conventional techniques, Gillette said.

The technique is described this month in the journal of the Royal Society of Chemistry – Lab on a Chip.

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Neural reductionism at its best, eh? By culturing individual neurons and small groups of neurons, and learning how to supply the needed growth factors and nutrients without potentially contaminating plasmas and serums, neuroscientists can begin to understand these cells at a very basic level. Then they can learn to combine them, along with their support (glial) cells. Eventually they can add capillaries, lymph vessels, etc. and move up from there. By understanding each level of complexity as they develop, neuroscientists can better envision the combinatorial possibilities.

One of the more intriguing uses to which these micro-cultures can be put, is brain-machine interfaces. By learning to develop neurons and small groups of neurone (micro-nets) away from normal biological substrate (brains, blood, and tissue fluid), it is only a short step to micro-channel support chips that can function as interfaces to machines. Neurophilosopher discusses a related development.

This is an important development. Together with improved techniques for manipulating neuronal stem cells and progenitors, this development points directly to better "wet" neural net models of brain, and better nerve-machine interfaces.