Growing Small Brains on Chips -- What Can We Learn?

Scientists can now grow interconnecting cultures of nerve cells on microfluidic chips in the lab, to study neuron growth and synaptic activity. MIT postdoc Peng Shi is hoping to use that technique to learn more about neurodegenerative diseases like Alzheimer's.

a team of MIT researchers has developed a new way to grow synapses between cells in a laboratory dish, under very controlled conditions that enable rapid, large-scale screens for potential new drugs.

Using their new technology, the researchers have already identified several compounds that can strengthen synapses. Such drugs could help compensate for the cognitive decline seen in Alzheimer’s, says Mehmet Fatih Yanik, the Robert J. Shillman (1974) Career Development Associate Professor of Electrical Engineering at MIT and leader of the research team. Yanik and his colleagues described the technology in the Oct. 25 online edition of the journal Nature Communications.

Lead author of the study is MIT postdoc Peng Shi. _MedXpress_Physorg

Peng Shi began working with this technique for studying synapses when he was doing PhD work at Columbia. Here is an earlier study using similar microfluidic chips for studying axon guidance in development.

Proper function of the nervous system relies on the formation of precise connections between nerve cells that span complex substrates and long distances. Axon guidance is a key process in establishing this architecture, in which cells must appropriately integrate and respond to multiple signals presented in the extracellular environment 1. These cues come from a wide range of signaling systems, including “canonical” guidance molecules (e.g. Netrins, Slits, Semaphorins, and Ephrins), morphogens (e.g. Hedgehog, BMP, and Wnt families), growth factors (e.g. NGF, BDNF, HGF, and FGFs), and cell adhesion proteins (e.g. N-cadherin, NCAM, L1-CAM). Extensive cross-talk between these pathways has been demonstrated, introducing additional layer of complexity to the mechanisms controlling axonal navigation. Moreover, guidance molecules that are often associated with extracellular matrix components are received and interpreted by nerve cells in a highly localized manner within the growth cones found at the tips of growing axons. Axon guidance is thus an intricate process occurring on a subcellular scale, requiring highly refined experimental techniques to study and manipulate.

Contemporary microfabrication methods have much promise for enhancing the tools that are used to study how localized signaling drives cell function. For example, Campenot chambers, which consist of millimeter-scale barriers that isolate axons and cell bodies into separate compartments, have been widely used to investigate local signaling by restricting the activity of pharmacological agents to distinct parts of the neuron 2. This allows localized study of receptors on the cell surface and limits the effects of detrimental or toxic drugs to the rest of the cell. Microfabricated versions of the Campenot chamber have been more recently developed that provide higher reproducibility and better compatibility with a broad range of nerve cells... _LabChip 2010 April 21

Abstract of Peng Shi's PhD thesis on using microfluidic labs-on-chips to study neuronal development and regeneration

Good overview of the use of microfluidic chambers for the study of synapses (PDF)

Why do I refer to such work as "growing small brains on chips?" Because that is the possiblity that this research promises for the future. Different chips can be fabricated to serve as scaffolds for different types of brain structures and substructures. One chip could host a cerebellum, another chip a hippocampus, another chip a prefrontal cortex . . . and so on. It sounds like an overly ambitious goal, considering how things currently stand, but then there is nothing wrong with looking far ahead -- as long as it is possible and useful to discover how to get there from here.

Very tedious work, you say? Yes, but we have vastly improved tools of micro- and nano-fabrication, along with exponentially improving computational tools, and rapidly increasing knowledge of the genetics and molecular dynamics of neuronal activity and needs.

It is the nature of nerve cells to exhibit spontaneous activity, both in normal development, and in cell culture. As neuronal cultures become more sophisticated -- grown on crafted scaffolds and supplied with a specialised combination of humoral factors -- it will be possible to grow miniature models of brain components which exhibit spontaneous activity. As you then interconnect the different models together, you might expect the different miniature conglomerates to begin communicating, spontaneously. And so on.

This is not what Peng Shi and other researchers are doing. They are looking at synaptic strength, and trying to find ways to strengthen synapses in hopes of finding ways to treat neurodegenerative diseases. Such research is extremely important, and critical to the needs of modern, aging societies.

But growing miniature, working brains using future iterations of similar technologies as used by Peng Shi is something of a holy grail to the Dr. Frankensteins among us. You know who you are.

The aims of such in vitro whole brain modeling are largely theoretical at this point, but who knows? We may eventually find the cure to the Idiocracy and the Age of Zombies.

More: Brian Wang presents links to an MIT article about this research and a link to the study.

Supplementary information (PDF)