Named for their dense, moss-like appearance, mossy cells in the hippocampus are known to play key roles in memory. Loss of mossy cells is associated with temporal lobe epilepsy (TLE), a common form of adult epilepsy marked by recurring convulsive seizures with an increased risk of cognitive deficits. A new study now establishes a role for these mossy cells in directly controlling seizures and spatial memory. The recent publication in Science comes from a team from Stanford University.
"This study would not have been possible without the rapid advancement of technology, thanks in part to the BRAIN Initiative, which has encouraged scientists to develop innovative instruments and new ways to look at the brain," said senior co-author Ivan Soltesz. "It's remarkable that we can manipulate specific brain cells in the hippocampus of a mouse. Using 21st century tools brings us closer than ever to unlocking the mysteries behind this debilitating disease."
The team used a combination of optogenetic, electrophysiological (EEG), and behavioral methods to study mossy cells in a TLE mouse model. Focal seizures originate in one area of the brain and can be monitored by EEG scans. When the team detected focal seizures from the scans, they tried “switching on or off” the mossy cells. They found that when the cells are turned on, the seizures do not become convulsive. Whereas when the mossy cells are turned off, convulsive seizures are more likely to occur.
Groups of mice were then placed in a test chamber with two identical items. The following day, one of the items are replaced with a different one (to test for object recognition), or moved to new location (to test for spatial memory). The team found that the epileptic mice had difficulties with spatial memory. This forgetful behavior was similarly induced when the mossy cells were turned off, suggesting that in addition to preventing convulsive seizures, mossy cells are also important to memory. Ability to recognize objects, however, appear unaffected.
"The role of mossy cells in epilepsy has been debated for decades. This study reveals how critical these cells are in the disease, and the findings suggest that preventing loss of mossy cells or finding ways to activate them may be potential therapeutic targets," said Vicky Whittemore, Ph.D., program director at National Institute of Neurological Disorders and Stroke (NINDS). NINDS provided funding for the study.