A study of gene activity in the hippocampus of the brain, led by researchers at UT Southwestern, has identified marked differences between the anterior and posterior portions of the region. The findings, published today in Neuron, could shed light on various brain disorders that affect the hippocampus and may eventually help lead to new specific treatments.
“These new data reveal molecular-level differences that allow us to see the anterior and posterior hippocampus in a completely new way,” says study leader Genevieve Konopka, Ph.D., associate professor of neuroscience at UTSW .
She and co-leader of the study, Bradley C. Lega, MD, associate professor of neurological surgery, neurology, and psychiatry, explain that the human hippocampus is typically considered a uniform structure with key roles in memory, space navigation. and the regulation of emotions. However, some research has suggested that the two ends of the hippocampus — the anterior, which points down toward the face, and the posterior, which points upward toward the back of the head — take on different tasks.
Scientists have speculated that the anterior hippocampus may be more important for emotion and mood, while the posterior hippocampus may be more important for cognition. However, says Konopka, a Jon Heighten researcher at Autism Research, researchers had not yet explored whether there are differences in gene activity between these two halves.
For the study, Konopka and Lega, both members of Peter O’Donnell Jr. Brain Institute, and colleagues isolated samples from the anterior and posterior hippocampus from five patients from whom the structure was removed to treat epilepsy. Seizures often originate in the hippocampus, says Lega, who performed the surgeries. Although brain abnormalities trigger these seizures, microscopic analysis suggested that the tissues used in this study were anatomically normal.
After removal, samples were subjected to single-core RNA sequencing (snRNA-seq), which was evaluated gene activity in individual cells. Although snRNA-seq showed mostly the same types of neurons and the support cells reside in both sections of the hippocampus, the activity of specific genes in the excitatory neurons — those that stimulate fire in others. neurons – varied significantly between the anterior and posterior parts of the hippocampus. When the researchers compared this set of genes with a list of genes associated with psychiatric and neurological disorders, found significant coincidences. Nothing associated with mood disorders, as major depressive disorder or bipolar disorder, used to be more active in the anterior hippocampus; on the contrary, people associated with cognitive disorders, such as autism spectrum disorder, used to be more active in the posterior hippocampus.
Lega points out that the more researchers are able to appreciate these differences, the better they will be able to understand the disorders in which the hippocampus is involved.
“The idea that the former and the latter hippocampus representing two different functional structures is not entirely new, but it has been underestimated in clinical medicine, “he says.” When we try to understand the processes of the disease, we have to keep that in mind. ”
Fatma Ayhan et al, Resolution of cellular and molecular diversity along the anterior-posterior axis of the hippocampus in humans, Neuron (2021). DOI: 10.1016 / j.neuron.2021.05.003
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UT Southwestern Medical Center
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