September 27, 2004

UCSD Medical Researchers Find Degree Of Hippocampus
Damage Determines Effect On Spatial & Recognition Memory

By Sue Pondrom

Spatial memory is more vulnerable than object recognition memory when damage occurs in the brain’s memory processing center, the hippocampus, according to memory specialists at the University of California, San Diego (UCSD) School of Medicine in a study published the week of September 27, 2004 in the online edition of the Proceedings of the National Academy of Sciences.

“Our findings have implications for understanding psychiatric and neurological disease that affect the hippocampus and related medial temporal lobe structures,” said the study’s first author, Nicola J. Broadbent, Ph.D., a post doctoral fellow in the UCSD Department of Psychiatry.

Damage to the hippocampus can occur following lack of oxygen such as during cardiac arrest and the degree of damage can vary with the duration of the hypoxia, or oxygen deprivation. Psychiatric illnesses such as schizophrenia, post-traumatic stress disorder and depression are often associated with modest reductions in hippocampal volume. While researchers have known that the hippocampus, together with other medial temporal lobe structures, is important for the acquisition of new memories, little has been known about the effects of small amounts of hippocampal damage or how the extent of damage is related to function.

In studies with rats, the researchers found that spatial memory was impaired with as little as 30 to 50 percent of damage to the hippocampus, while object recognition memory remained intact until the animals were given larger lesions that encompassed 75 to 100 percent of hippocampal volume. Spatial memory includes such tasks as retention of geographical layouts or interiors of a house; object recognition memory calls upon the ability to remember stimuli or objects that were previously experienced.

In the experiments, 148 male rats received either sham lesions (an incision but no damage to the hippocampus) or actual lesions that damaged the hippocampus in various degrees, from 5 to 100 percent. Spatial memory training was conducted daily for five days in a standard water maze with a retractable platform. The object recognition task involved exposure to two identical objects, removal to the home cage for three hours, then a return to the test chamber with one previously seen object and a new object. Rats without damage to the hippocampus typically remember the previously seen object, and spend most of their time investigating the new, and now more interesting object.

Following administration of the lesions, the scientists found that all three groups of rats (30-50 percent, 50-75 percent and 75-100 percent lesions) had significantly more difficulty learning the spatial location of the platform than did the sham lesion group. In addition, the greater the amount of hippocampal damage, the more poorly the rat remembered the platform location.

In the object recognition tests, the sham group and the rats with lesions encompassing 50 to 75 percent of the hippocampus performed comparably. Not until the lesion size in the hippocampus was 75-100 percent did the researchers see a difference in object recognition memory.

“These results show that under standard testing conditions for spatial and recognition memory, spatial memory performance requires more hippocampal tissue than does recognition performance,” said coauthors and study team leaders Robert E. Clark, Ph.D., and Larry R. Squire, Ph.D. “Our findings raise a number of interesting questions. For instance, why does spatial memory require more intact tissue and what does this say about information processing and information storage.”

Clark is a UCSD assistant professor of psychiatry and neurosciences and Squire a UCSD professor of psychiatry and neurosciences. Both are research scientists at the VA San Diego Healthcare System.

The study was funded by the National Institute of Mental Health, the Medical Research Service of the Department of Veterans Affairs, the Metropolitan Life Foundation, the National Institute on Aging, the National Science Foundation, the McDonnell Foundation and an Effie Beeman young investigator award from the National Alliance for Research on Schizophrenia and Depression.

Media Contacts: Sue Pondrom (619) 543-6163