The Gap between the Brain and a Petri Dish
Due to the nature of the brain, it does not lend itself to being poked and probed by curious researchers. Thus, neurological research is highly dependent on the use of cell cultures. Improvements in stem cell technology have greatly facilitated use of neuronal cultures for determining basic principles of the central nervous system. However, such convenience comes with an important caveat: that of in vivo relevance.
Neuronal cultures derived from stem cells are cultured in media to promote neural differentiation and survival, with it being assumed that correct neuronal functioning would follow. However, Fred Gage, a Professor at the Salk Institute for Biological Studies, and colleagues have recently published a PNAS paper demonstrating that this is not the case. Gage and colleagues used a range of electrophysiological techniques – including patch clamping, calcium imaging, and microelectrode arrays – to probe neuronal activity in classic culture media. They identified that many crucial neurophysiological properties were altered under these conditions, including the spontaneous generation of action potentials, and both inhibitory and excitatory synaptic activity. This revelation has greatly contextualised the clinical significance of neuronal cultures, and their shortcomings, in classical media, calling into question the reliability of previous studies.
To resolve this issue, Gage and co-workers developed their own neuronal culture medium, BrainPhysTM. The authors establish that with the addition of serum-free supplements, BrainPhysTM is able to support both neuronal survival and fundamental synaptic activity of stem cell derived neurons. Additionally, though developed for human cells, the authors found that BrainPhysTM also supports rodent tissue derived neurons. The authors are now collaborating with STEMCELL Technologies to make BrainPhysTM commercially available.
As many neurological disorders are related to synaptic activity, disrupted neuronal activity in culture may confound the delineation of disease mechanisms. Thus, the improved neurological fidelity of BrainPhysTM offers an opportunity to understand disease pathologies in a way that was previously unavailable to us.
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