How do different parts of the brain communicate with each other during learning and memory training? A new study by researchers at the University of California at San Diego takes the first step to answer this fundamental question in neuroscience.
The study was made possible by the development of 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 various two-way communication patterns occur between two brain regions known to play a role in learning and memory formation – the hippocampus and the cerebral cortex. Researchers also show that these different modes of communication are linked to events called high wave ripples, which occur in the hippocampus during sleep and rest.
The researchers published their results on April 19 in Neuroscience of nature.
“This technology was developed in particular to simultaneously study interactions and communications between different regions of the brain,” said co-corresponding author Duygu Kuzum, professor of electrical and computer engineering at UC San Diego Jacobs School of Engineering. “Our neural implant is versatile; it can be applied to any area of the brain and can allow the study of other cortical and subcortical brain regions, not just the hippocampus and cerebral cortex.”
“Little is known about how various regions of the brain work together to generate cognition and behavior,” said Takaki Komiyama, professor of neurobiology and neuroscience in the School of Medicine and the Division of Biological Sciences at the ‘UC San Diego, who is the study’s other co-correspondent author. . “Unlike the traditional approach of studying one area of the brain at a time, the new technology introduced in this study will begin to allow us to learn how the brain as a whole works to control behaviors and how the process might be compromised in the process. neurological disorders. “
The neural implant consists of a thin, transparent and flexible polymer strip made with an array of micrometric gold electrodes, on which platinum nanoparticles have been deposited. Each electrode is connected by a micrometer thick wire to a custom printed circuit board. Kuzum’s laboratory developed the implant. They worked with Komiyama’s lab to perform brain imaging studies in transgenic mice.
Design a multi-use neural probe
What makes this neural implant unique is that it can be used to monitor activity in multiple regions of the brain at the same time. It can record electrical signals from single neurons deep inside the brain, such as in the hippocampus, while imagining large areas like the cerebral cortex.
“Our probe allows us to combine these modalities in the same experiment in a transparent way. It cannot be done with current technologies, ”said Xin Liu, a doctorate in electrical and computer engineering. student in Kuzum’s lab. Liu is a co-lead author of the study with Chi Ren, a recent PhD in Biological Sciences from UC San Diego. graduate who is now a postdoctoral researcher in the Komiyama laboratory, and Yichen Lu, a doctorate in electrical and computer engineering. student in Kuzum’s lab.
Several design features make multi-regional surveillance possible. The first is that this probe is flexible. When inserted deep into the brain to monitor an area like the hippocampus, the protruding part of the brain can be bent and make room for a microscope to be lowered close to the surface for imaging of the cerebral cortex. at the same time. Conventional neural probes are rigid, so they interfere with the microscope; therefore, they cannot be used to monitor deep brain structures when imaging the brain surface. And while the UC San Diego team’s neural probe is soft and flexible, it’s designed to resist buckling under pressure during insertion.
Another important feature is that this probe is transparent, which gives the microscope a clear field of view. It also does not generate shadows or additional noise during imaging.
Explore the fundamental questions of neuroscience
The motivation for this study was to get 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 the cerebral cortex. But how exactly is this communication done? And which brain region initiates this communication: the hippocampus or the cerebral cortex? These types of questions have gone unanswered because it is very difficult to study these two regions of the brain simultaneously, Kuzum said.
“We wanted to study the nature of corticosteroid-hippocampal interactions, so we built a technology to explore this neuroscience problem,” she said.
The researchers used their probe to monitor the activity of the hippocampus and cerebral cortex in transgenic mice. Specifically, they monitored activity before, during, and after the oscillations that occur in the hippocampus, called sharp wave ripples.
Their experiments revealed that communication between the hippocampus and the cerebral cortex is bilateral: sometimes the cortex initiates communication, other times it is the hippocampus. It’s an important first clue for understanding interregional communication in the brain, the researchers said.
“The hippocampal-cortical interaction is important in the consolidation and recovery of memory,” said Ren. “The two-way communication we have reported here is different from the conventional notion that the cortex passively receives information from the hippocampus. Instead, the cortex is actively involved in encoding information in the brain and can play a role. instructive role during memory consolidation and reclamation. “
“We can now start new studies to find out how processes like learning and memory occur,” Kuzum said. “For example, when the brain acquires new information, how does the hippocampus transfer memory to the cortex for storage, or does the cortex send a signal to transfer memory? Our results show that communication can be initiated by either, but to go beyond that we would need to do some behavioral studies. “
This study also reveals that there are diverse and distinct modes of communication between the hippocampus and the cerebral cortex. Researchers have found that the hippocampus communicates with at least eight different parts of the cerebral cortex whenever high-pitched wave ripples occur. Additionally, each of these eight patterns of cortical activity is linked to a different population of neurons in the hippocampus.
“These results suggest that the interactions between regions of the brain, and not just between the cortex and the hippocampus, can be fundamentally diverse and flexible. Therefore, multiple regions of the brain can work effectively together to generate cognition and behavior that adapt quickly to changing environments, ”said Ren.
This research was supported by the Office of Naval Research (N000142012405 and N00014162531), the National Science Foundation (ECCS-2024776, ECCS-1752241 and ECCS-1734940) and the National Institutes of Health (R21 EY029466, R21 EB026180, DP2 EB030992 , R01 NS091010A, R01 EY025349, R01 DC014690, R21 NS109722 and P30 EY022589).