Neurons that once encoded a person's memories are now helping researchers identify genetic targets that may one day help preserve memory and slow cognitive decline in others.
In a study published in the journal Nature, UCLA Health and University of Texas Southwestern Medical Center researchers used real human brain tissue samples, donated by several neurosurgery patients and kept alive in a lab for several days, to test the underlying mechanisms of deep brain stimulation.
Deep brain stimulation, which uses electrical impulses to alter how neurons communicate delivered by implants in the brain, has shown significant promise in treating various neurological or psychiatric disorders such as Parkinson’s disease and obsessive-compulsive disorder.
Recent studies have tested whether stimulation could address the growing national issue of cognitive decline. But how this stimulation affects different types of human brain cells and the underlying genes involved is not well understood and has only been directly tested on lab-grown or animal tissues. The new study is believed to be the first to mimic electrical patterns similar to deep brain stimulation on living, human-derived brain tissue outside of the body.
After applying electrical stimulation, the researchers found that brain cells became more synchronized in the way they communicated, which is a pattern believed to help the brain form memories. In parallel, the researchers measured how stimulation altered gene expression across different types of brain cells by isolating individual cell nuclei and recording each cell type’s genetic activity.
The findings reveal that neurons and even non-neuronal support cells, such as astrocytes, switch on their own distinct genetic programs in response to stimulation, offering a new window into how the human brain responds to these therapies at the molecular level. Similar patterns were also observed in tissues from individuals who had underwent brain stimulation prior to the tissue being removed, showing that these effects were occurring in the body as well.
“Not only was it a privilege and challenge to work with donated living human brain tissue, but to see it reveal the genes and cell types underlying human brain plasticity as new targets for future therapies makes the work feel even more meaningful,” said the study’s senior author Genevieve Konopka, chair of the Department of Neurobiology at UCLA Health. “By understanding exactly which genes turn on in which cells during stimulation, we can start to design more precise approaches to deep brain stimulation and potentially augment this clinical strategy with pharmacological therapies to help slow cognitive decline.”
The brain tissues samples were derived from the temporal cortex, which is located on the sides of the outermost layer of the brain, a region critical for memory and related cognitive processes. Researchers acknowledge that further investigation is needed to determine the molecular effects of long-term stimulation, how the stimulated cells affect neighboring cells and how the therapy affects deeper brain regions, which are more difficult to acquire from living donors.
