Multiregional brain-on-a-chip to study disorders developed

Researchers from Harvard University have developed a multiregional brain-on-a-chip that models the connectivity between three distinct regions of the brain. The in-vitro model was used to extensively characterise the differences between neurons from different regions of the brain and to mimic the system's connectivity.

"The brain is so much more than individual neurons. When modelling the brain, you need to be able to recapitulate that connectivity because there are many different diseases that attack those connections," said Ben Maoz, a postdoctoral fellow in the Harvard John A Paulson School of Engineering and Applied Sciences (SEAS).

Researchers from the Disease Biophysics Group at SEAS and the Wyss Institute modelled three regions of the brain most affected by schizophrenia - the amygdala, hippocampus and prefrontal cortex. They began by characterising the cell composition, protein expression, metabolism, and electrical activity of neurons from each region in vitro.

"It's no surprise that neurons in distinct regions of the brain are different but it is surprising just how different they are," added Stephanie Dauth, co-first author of the paper. "We found that the cell-type ratio, the metabolism, the protein expression and the electrical activity all differ between regions in vitro. This shows that it does make a difference which brain region's neurons you're working with," Dauth noted.

The team then looked at how these neurons change when they're communicating with one another. "When the cells are communicating with other regions, the cellular composition of the culture changes, the electrophysiology changes, all these inherent properties of the neurons change," said Maoz in a paper published in the Journal of Neurophysiology.

The team doped different regions of the brain with the drug Phencyclidine hydrochloride -- commonly known as PCP which simulates schizophrenia. The brain-on-a-chip allowed the researchers for the first time to look at both the drug's impact on the individual regions as well as its downstream effect on the interconnected regions in vitro.

"The brain-on-a-chip could be useful for studying any number of neurological and psychiatric diseases, including drug addiction, post traumatic stress disorder and traumatic brain injury," the authors wrote.