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He rolandi group in collaboration with the braingeneers have developed a new plug-and-play bioelectronic system that allows researchers to precisely control neuronal activity in cortical organoids, which will help unlock new discoveries about how brains form neuronal circuits and the basis of degenerative and chronic diseases. neurodevelopment. Beyond simply studying organoids, their system can be adapted for use in a wide range of biological experiments.
The research team, with electrical and computer engineering professor Marco Rolandi, electrical and computer engineering associate professor Mircea Teodorescu, and UCSC Genomics Institute research scientist Mohammed Mostajo-Radji as co-senior authors, describe their novel system in a new paper In the diary Cellular reporting methods. Former UCSC postdoc Yunjeong Park and current UCSC Ph.D. The student Sebastián Hernández led the research as co-authors.
“This work with brain organoids is an important proof of concept, because organoids are becoming the standard for looking at how external stimuli affect organs,” Rolandi said.
While organoid models are increasingly popular for the study of brain development, function and evolution, currently existing methods for manipulating organoids are still rather unsophisticated and rely on optical methods or the rough application of chemicals that do not allow researchers to control precisely. the moment of the manipulations.
However, the new methods described in this article allow researchers to use bioelectronic delivery of ions and neurotransmitters to models to achieve precise, time-controlled experiments. The system is also easily integrated into existing experiments as it is simply placed on top of a cell culture dish.
“This paper offers the ability to manipulate highly relevant models with high temporal precision,” Mostajo-Radi said.
Modulating neuronal activity can help scientists better understand the wide range of human diseases that are known to be associated with hyperactivity in certain areas of the brain, such as Parkinson’s disease or epilepsy. Controlling and modulating neuronal activity in brain organoids can help researchers learn more about these conditions and develop better methods to monitor and treat them.
For example, researchers could closely mimic the drug-cell interaction that occurs in real treatment using the high-precision system to see how dose amounts of various drugs interact with cells in an organoid at a defined time. Using small amounts of a drug makes experiments “reversible,” as the organoid can return to its original state, which is especially important when researchers are rapidly testing how various drugs interact with organoids grown from cells. mother of a patient.
“Brain cells communicate through electrical impulses and chemical signals, so using the neurons’ own ‘chemical language’ could improve treatment outcomes for specific diseases,” Hernández said. “This can be achieved using ion pumps as therapeutic devices.”
Modulating neural activity can also help researchers better understand how neural circuits work: the process by which neural signals propagate and spread throughout the brain. By slowing down, speeding up, or interrupting a signal through precise manipulation of ions, researchers can investigate how signals are transmitted.
“It’s like having a dimmer switch for the circuits in the brain, where we can increase activity or calm it down,” Park said. “This tool opens up new possibilities for exploring how our brains function and develop, potentially revolutionizing our approach to neurological research and treatment.”
The bioelectronic system includes an integrated ion pump that can be placed directly on top of a cell culture dish. This modular system makes it easy for scientists to integrate the system into their experiments. In the past, it has been difficult to integrate these types of bioelectronic devices with cell cultures because a researcher would have to grow their cells directly on the device, adding further complexity to the already difficult task of growing organoids.
“Instead of adapting biology to bioelectronics, we have adapted bioelectronics to biology,” Rolandi said.
While the researchers focused on the application of their system to organoids in this paper, Rolandi emphasized that the highly modular system can be used in a wide range of biology experiments that would benefit from the precise delivery of ions to a cell plate.
“The importance of the platform is that it goes beyond organoids,” Rolandi said. “Any type of biological system, whether it’s an organoid, a cell culture, or a bacterial culture, is likely to be in a well plate, and our system is plug-and-play, you just drop it on top.”