Your brain on a petri dish: how cerebral organoids are changing neuroscience

As an animal researcher, part of my job is to think about the limitations and ethical practices surrounding animal models. Like most animal researchers, I use mice to approximate human diseases. A lot of times we can get pretty close, but animal models, aside from the ethical concerns they raise, can never perfectly recapitulate human disease. Neuroscience applications are perhaps the most difficult to model – after all, our brains are what make us human. It’s very hard to create suitable animal models for depression or anxiety, and those are some of the easier mental disorders to study. Forget about being able to adequately study poorly understood disorders like autism or schizophrenia.

That’s why cerebral organoids – brains in a petri dish, for the uninitiated – are so exciting. The organoids, which consist of several layers of human neurons organized into roughly spherical shapes, were first developed by Drs. Madeline Lancaster and Jurgen Knoblich in 2013. These are not true brains – to my knowledge no one has yet attempted such a Frankensteinian endeavor – but tiny orbs of tissue that start out as humble stem cells and self-organize into something remarkably akin to human brain structures.

nature12517-f1

A stained section of a cerebral organoid. Stains for neural progenitors and neurons show defined regions that mimic those in developing human brains. Photo credit: Madeline Lancaster, Nature 2013.

Since their inception, cerebral organoids have already helped researchers make strides in our understanding of brain development. A scientist by the name of Flora Vaccarino used these cerebral organoids to study the developmental differences between a small cohort of autistic males and their neurotypical family members. The study found that organoids derived from autistic subjects displayed faster growth of inhibitory neurons* than the family member controls did. This finding is consistent with previous studies that identify abnormal levels of the inhibitory neurotransmitter GABA* in autistic subjects, as well as the increased head and brain size often characteristic of autism. (*For a quick neuroscience primer, scroll to the end of the article!)

Ultimately, Vaccarino’s group discovered that overexpression of a gene called FOXG1 was largely responsible for the difference. Although further studies will be needed to apply these results broadly, the study was important not only for what it discovered but for how the discovery was made – these miniature brains are powerful tools for studying brain development. They provide a living, growing system that can be readily manipulated to solve pressing problems. Just last week it was reported that Zika virus dramatically slows neural growth in cerebral organoids, supporting the hypothesis that Zika causes microcephaly in developing babies.

Human-Mini-Brains

Those floating chunks are cerebral organoids, tiny models of developing human brains. Researchers use a spinning bioreactor to keep the organoids alive.

These tiny brains in petri dishes hold a lot of promise for society. They could help us answer a lot of big questions: who we are, what makes us human, why some people’s brains work differently from others’. Although it’s a relatively new technology, researchers are beginning to use cerebral organoids to study autism, Alzheimer’s, Down syndrome, schizophrenia, and a range of other disorders. My personal hope is that the insights from this research will lead to better ways of communicating with and helping people who think differently and sometimes have trouble fitting into “neurotypical” society. My other personal hope is that organoids (cerebral and otherwise) will help us move away from animal research by providing a more accurate model to work with. The National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs) agrees, awarding a 3Rs prize to Dr. Lancaster for her development of cerebral organoids.

Thanks for reading! Please ask questions, tell me about your own research and experiences, and deliver any snide remarks in the comments section below.

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*In case you’re not up to date on your neuroscience, a handy primer:

  • The brain is composed of neurons, which communicate with each other via electrical signals.
  • Molecules called neurotransmitters help regulate whether or not neurons produce an electrical signal.
  • Inhibitory neurotransmitters, like GABA, make an electrical signal less likely. The neurons that produce and excrete GABA are called inhibitory neurons.
  • Excitatory neurotransmitters make an electrical signal more likely. The neurons that produce and excrete excitatory neurotransmitters are called excitatory neurons.

Excitation and inhibition in the brain are equally important, and everyone has both excitatory and inhibitory neurons. Your excitatory neurons are important because they relay information. For instance, if someone calls your name, your excitatory neurons respond to that stimulus and tell you you’re being called. The inhibitory neurons are there to make sure your brain stops responding to that stimulus, saving you from endlessly hearing your name being called.

That’s a very simple example, and excitatory and inhibitory neurons have myriad and complex functions, which is why we can’t reduce Dr. Vaccarino’s findings to mere “brain chemistry” (after all, the brain is not a stew). It’s unclear why autistic brains appear to have excess inhibitory neurons or what this implies. This doesn’t even mean that autistic brains are “less excited” – high GABA levels can also be a means of balancing out high levels of excitatory signals. This finding is one of many pieces to the puzzle that we will put together as we strive to understand autism.

For a more in-depth lesson on neural signaling, head over to this Wikiversity lesson. Also check out the other lessons in the course if you have a general interest in neuroscience. 

 

Jessica (Editor)
10891702_10152475816767115_155735200795992761_nJess is a fourth year biology PhD student who studies the liver and its regenerative capabilities. In her admittedly limited free time, she enjoys traveling, writing, and being outdoors.
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