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Brain scans and behavioral tests of California sea lions that stranded on shore show how an algal toxin disrupts brain networks, leading to deficits in spatial memory, according to a study to be published Dec. 18 in Science. The new findings by scientists at аÄÃÅÁùºÏ²ÊÄÚÄ»ÐÅÏ¢ Santa Cruz, аÄÃÅÁùºÏ²ÊÄÚÄ»ÐÅÏ¢ Davis and the Marine Mammal Center in Sausalito, California, suggest that chronic exposure to the toxin domoic acid, produced by naturally occurring marine algae, affects sea lions' ability to navigate in their ocean habitat and survive in the wild.

Blooms of the toxic algae typically occur in the spring and fall along the California coast, but have been increasing in frequency and severity. Hundreds of sea lions strand on California beaches every year with symptoms of domoic acid poisoning, including disorientation and seizures.

A team led by Peter Cook, then a graduate student at the University of California, Santa Cruz, and now at Emory University, studied 30 California sea lions undergoing veterinary care and rehabilitation at the in Sausalito. Researchers administered behavioral tests to assess spatial memory and performed brain imaging (MRI) to see the extent of brain lesions in the affected animals.

Damage to the hippocampus, a part of the brain involved in memory, is often seen in sea lions with domoic acid poisoning, Cook said.

"In this study, we were able to correlate the extent of hippocampal damage to specific behavioral impairments relevant to the animals' survival in the wild," he said.

Working with Professor Charan Ranganath’s Dynamic Memory Laboratory at the аÄÃÅÁùºÏ²ÊÄÚÄ»ÐÅÏ¢ Davis Center for Neuroscience, Cook adapted behavioral tests usually used to assess memory in rats to sea lions. For example, in a "T-maze," an animal has to remember that if it got a treat by turning right, the next time it takes the test it gets a treat by turning left. Cook also consulted with the аÄÃÅÁùºÏ²ÊÄÚÄ»ÐÅÏ¢ Davis Alzheimer’s Disease Center on how to use MRI scans to quantify damage to brain structures such as the hippocampus.

With MRI, the researchers could see structural damage in the brains of affected sea lions, especially in the hippocampus. This looped structure in the center of the brain is known to be important for memory processes in humans and rodents. Animals with damage to the hippocampus showed impaired performance on short- and long-term spatial memory tasks, the researchers found.

"We could see structural differences, so we decided to get some functional data while the animals were in the scanner," Ranganath said. While an anesthetized animal is in the scanner, brain regions continue to share information back and forth.

With a grant from Siemens, the team was able to use equipment never previously used for marine mammals to look at how different brain regions talk to each other. They found that in addition to visible damage to the hippocampus, there were effects on interactions between the hippocampus and other brain structures, notably the thalamus.

"This is the first evidence of changes to brain networks in exposed sea lions, and suggests that these animals may be suffering a broad disruption of memory, not just spatial memory deficits," Cook said.

The study provides the missing link, Ranganath said, between the environmental degradation that leads to toxic algal blooms and sea lion strandings.

"We didn't know exactly why the algae lead to strandings. But sea lions are dynamically foraging — and for an animal like that, if you don’t know where you are, you have a big problem," he said.

These memory deficits may also help explain anecdotal reports of sea lions showing up in unusual places far outside their normal range, either too far out at sea or inland far from the coast, according to co-author Colleen Reichmuth, director of the at аÄÃÅÁùºÏ²ÊÄÚÄ»ÐÅÏ¢ Santa Cruz, where the behavioral tests were conducted.

Brain lesions may develop over time with repeated exposure to the toxin. Sea lions with symptoms of brain damage strand on beaches all year round, even when there is no active bloom of the toxic algae.

"What isn't well understood yet is the dose response," Cook said. "We don't know how heavy the exposure needs to be, or how often repeated, to cause this kind of brain damage, and we don't know the effects of repeated low-dose exposure."

In addition to Cook, Ranganath and Reichmuth, co-authors include Andrew Rouse at аÄÃÅÁùºÏ²ÊÄÚÄ»ÐÅÏ¢ Santa Cruz; Laura Libby and Baljeet Singh at аÄÃÅÁùºÏ²ÊÄÚÄ»ÐÅÏ¢ Davis; Sophie Dennison, Kris Kruse-Elliott, and Jim Stuppino at AnimalScan Advanced Veterinary Imaging, Redwood City; Owen Carmichael at Pennington Biomedical Research Center, Baton Rouge; Vanessa Fravel, Lorraine Barbosa and Frances Gulland at the Marine Mammal Center, Sausalito; and William Van Bonn at the Shedd Aquarium, Chicago. This research was funded by the National Science Foundation and the David and Lucile Packard Foundation.