DALLAS – May 28, 2021 – A study of gene activity in the hippocampus of the brain led by researchers at UT Southwestern has identified significant differences between the anterior and posterior parts of the region. The results, published today in Neuron, could shed light on a variety of brain disorders affecting the hippocampus and could eventually lead to new, targeted treatments.

“These new data show differences at the molecular level that allow us to look at the anterior and posterior hippocampus in a whole new way,” says study director Genevieve Konopka, Ph.D., associate professor of neuroscience at UTSW.

She and study director Bradley C. Lega, MD, Associate Professor of Neurological Surgery, Neurology, and Psychiatry, explain that the human hippocampus is typically viewed as a unitary structure with key roles in memory, spatial navigation, and regulation of emotions. However, some research has found that the two ends of the hippocampus – the front, facing down toward the face and the back, facing up toward the back of the head – perform different roles.

Scientists have speculated that the anterior hippocampus might be more important for emotions and mood, while the posterior hippocampus might be more important for cognition. However, according to Konopka, a Jon Heighten Fellow in autism research, the researchers had yet to investigate whether there were any differences in gene activity between these two halves.

For the study, Konopka and Lega, both members of the Peter O’Donnell Jr. Brain Institute, and their colleagues isolated samples from both the anterior and posterior hippocampus from five patients whose structure had been removed to treat epilepsy. Seizures often originate from the hippocampus, explains Lega, who performed the operations. Although brain abnormalities trigger these seizures, microscopic analysis indicated that the tissue used in this study was anatomically normal.

After removal, the samples were subjected to single-core RNA sequencing (snRNA-seq), which assesses the gene activity in individual cells. Although snRNA-seq showed largely the same types of neurons and supporting cells in both sections of the hippocampus, the activity of certain genes in excitatory neurons – which cause other neurons to fire – varied significantly between the anterior and posterior parts of the hippocampus. When the researchers compared this group of genes to a list of genes associated with psychiatric and neurological disorders, they found significant similarities. Genes associated with mood disorders, such as Major depressive disorder or bipolar disorder, tended to be more active in the anterior hippocampus; Conversely, genes associated with cognitive disorders such as autism spectrum disorder tended to be more active in the posterior hippocampus.

The Lega notes that the more researchers can spot these differences, the better they will be able to understand disorders that involve the hippocampus.

“The idea that the anterior and posterior hippocampus represent two different functional structures is not entirely new, but it has been underestimated in clinical medicine,” he says. “When we try to understand disease processes, we have to keep that in mind.”

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Other UTSW researchers who contributed to this study are Fatma Ayhan, Ashwinikumar Kulkarni, Stefano Berto, Karthigayini Sivaprakasam, and Connor Douglas.

This work was supported by grants from the National Institutes of Health (NIH grants NS106447, T32DA007290, T32HL139438, NS107357), a seed grant from the University of Texas BRAIN Initiative (366582), the Chilton Foundation, the National Center for Advancing Translational Sciences of the NIH. funded (under the Center for Translational Medicine Award UL1TR001105), the Chan Zuckerberg Initiative (an advised fund to the Silicon Valley Community Foundation, HCA-A-1704-01747), and the James S. McDonnell Foundation 21st Century Science Initiative in Understanding Human Cognition ( Scholarship price 220 020 467).

Via the UT Southwestern Medical Center

UT Southwestern, one of the leading academic medical centers in the country, integrates groundbreaking biomedical research with exceptional clinical care and training. The institution’s faculty has won six Nobel Prizes and includes 25 members from the National Academy of Sciences, 17 members from the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty, with more than 2,800 employees, is responsible for breakthrough medical advances and is committed to quickly translating science-based research into new clinical treatments. UT Southwestern doctors care for more than 117,000 hospital patients, more than 360,000 emergency rooms in approximately 80 specialties, and oversee nearly 3 million outpatient visits annually.

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