Harvard researchers have developed a multiregional brain-on-a-chip that models the connectivity between three distinct regions of the brain and allows studying how diseases like schizophrenia impact different brain areas simultaneously. The chip could be useful for studying any number of neurological and psychiatric diseases, including drug addiction, post traumatic stress disorder, and traumatic brain injury, researchers said.

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," said Ben Maoz, postdoctoral fellow at Harvard University's John A Paulson School of Engineering and Applied Sciences (SEAS).

"It 's about the different types of cells and the connectivity between different regions of the brain. When modelling the brain, you need to be able to recapitulate that connectivity because there are many different diseases that attack those connections," Maoz said. Researchers 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," said Stephanie Dauth, former postdoctoral fellow in the Disease Biophysics Group at SEAS.

"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 are working with," Dauth said. The team also looked at how these neurons change when they are communicating with one another. They cultured cells from each region independently and then let the cells establish connections via guided pathways embedded in the chip.

The researchers then measured cell composition and electrical activity again and found that the cells dramatically changed when they were in contact with neurons from different regions. To demonstrate the chip's efficacy in modelling disease, 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 research was published in the Journal of Neurophysiology.