How do different parts of the brain communicate with each other during learning and memory formation? A new study by researchers at the University of California San Diego takes a first step at answering this fundamental neuroscience question.

The study was made possible by developing a neural implant that monitors the activity of different parts of the brain at the same time, from the surface to deep structures — a first in the field. Using this new technology, the researchers show that diverse patterns of two-way communication occur between two brain regions known to play a role in learning and memory formation — the hippocampus and the cerebral cortex. The researchers also show that these different patterns of communication are tied to events called sharp-wave ripples, which occur in the hippocampus during sleep and rest.

“Our neural implant is versatile; it can be applied to any area of the brain and can enable study of other cortical and subcortical brain regions, not just the hippocampus and cerebral cortex,” said Professor Duygu Kuzum.

The neural implant is made up of a thin, transparent, flexible polymer strip fabricated with an array of micrometer-sized gold electrodes, onto which platinum nanoparticles have been deposited. Each electrode is connected by a micrometers-thin wire to a custom-printed circuit board. It can record electrical signals from single neurons deep inside the brain, like in the hippocampus, while imaging large areas like the cerebral cortex.

Several design features make multi-region monitoring possible. One is that this probe is flexible. When it is inserted deep into the brain to monitor a region like the hippocampus, the part that sticks out of the brain can be bent down to make room for a microscope to be lowered close to the surface to do imaging of the cerebral cortex at the same time. Conventional neural probes are rigid, so they get in the microscope's way; as a result, they cannot be used to monitor deep brain structures while imaging the brain's surface. And even though this neural probe is soft and flexible, it is engineered to withstand buckling under pressure during insertion. Another important feature is that the probe is transparent, so it gives the microscope a clear field of view. It also does not generate any shadows or additional noise during imaging.

The motivation for this study was getting to the root of how different cognitive processes, such as learning and memory formation, occur in the brain. Such processes involve communication between the hippocampus and cerebral cortex. But how exactly does this communication happen? And which brain region initiates this communication: the hippocampus or the cerebral cortex? These types of questions have been left unanswered because it is very difficult to study these two brain regions simultaneously, said Kuzum.

The researchers used their probe to monitor the activity of the hippocampus and the cerebral cortex in transgenic mice. Specifically, they monitored activity before, during and after oscillations called sharp-wave ripples occur in the hippocampus. Their experiments revealed that communication between the hippocampus and cerebral cortex is two-sided: sometimes the cortex initiates communication, other times it's the hippocampus. This is an important first clue for understanding inter-region communication in the brain, the researchers said.

“The two-sided communication we reported here is different from the conventional notion that the cortex passively receives the information from the hippocampus. Instead, the cortex is actively involved in encoding information into the brain and may play an instructive role during memory consolidation and retrieval,” said Dr. Chi Ren, one of the researchers.

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