A research team led by UC Irvine neuroscientists has identified how the brain processes and stores emotional experiences as long-term memories. The research, performed on rats, could help neuroscientists better understand why emotionally arousing events are remembered over longer periods than emotionally neutral events, and may ultimately find application in treatments for conditions such as post-traumatic stress disorder.

The study shows that emotionally arousing events activate the brain’s amygdala, the almond-shaped portion of the brain involved in emotional learning and memory, which then increases a protein called “Arc” in the neurons in the hippocampus, a part of the brain involved in processing and enabling the storage of lasting memories. The researchers believe that Arc helps store these memories by strengthening the synapses, the connections between neurons.

The study appears in [26 July 2005] issue of the Proceedings of the National Academy of Sciences.

“Emotionally neutral events generally are not stored as long-term memories,” said Christa McIntyre, the first author of the paper and a postdoctoral researcher in the Department of Neurobiology and Behavior in UCI’s School of Biological Sciences, working with James L. McGaugh, research professor and a fellow at the Center for the Neurobiology of Learning and Memory. “On the other hand, emotionally arousing events, such as those of September 11, tend to be well-remembered after a single experience because they activate the amygdala.”

In their experiments, the researchers placed a group of rats in a well-lit compartment with access to an adjacent dark compartment. Because rats are nocturnal and prefer dark environments, they tended to enter the dark compartment. Upon doing so, however, they were each given a mild foot-shock – an emotional experience that, by itself, was not strong enough to become a long-lasting memory. Some of the rats then had their amygdala chemically stimulated in order to determine what role it played in forming a memory of the experience.

When they placed the rats that received both the mild foot-shock and the amygdala stimulation back in the well-lit compartment, the researchers found the rats tended to remain there, demonstrating a memory for the foot shock they had received in the dark compartment. These rats, the researchers found, also showed an increase in the amount of the Arc protein in the hippocampus. On the other hand, rats that received only the mild foot-shock and no amygdala stimulation showed no increase in Arc protein. When placed in the well-lit compartment, they tended to enter the dark compartment, suggesting they didn’t remember the foot shock.

“In a separate experiment, we chemically inactivated the amygdala in rats very soon after they received a strong foot-shock,” McIntyre said. “We found the increase in Arc was reduced and these rats showed poor memory for the foot shock despite its high intensity. This also shows that the amygdala is involved in forming a long-term memory.”

The brain is extremely dynamic, McIntyre explained, with some genes in the brain, called “immediate early genes,” changing after every experience. “We know the level of the immediate early gene that makes the Arc protein increases in the brain, simply in response to an exposure to a new environment,” she said. “Our findings show that this gene makes more Arc protein in the hippocampus only if the experience is emotionally arousing or important enough to activate the amygdala and to be remembered days later.”

The researchers were surprised to find no change in the gene that produced the Arc protein when the rat’s amygdala was stimulated. “We weren’t expecting the gene to be uncoupled from the Arc protein,” McIntyre said. “We thought an activation of the amygdala would create more gene activation in the hippocampus. But we saw the same amount of the gene in the rats, regardless of the amygdala treatment. It was the Arc protein, created by the gene, that was different. This gives us new insight into the way lasting memories are stored.”

The research was supported by several grants from the National Institutes of Health. In addition to McIntyre and McGaugh, co-authors of the study include Oswald Steward, UCI; Teiko Miyashita, Kristopher D. Marjon and John F. Guzowski, the University of New Mexico Health Science Center; and Barry Setlow, Texas A&M University.

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UCI Press Release
26 July 2005

Scientists have found that the site in the brain that controls language in right-handed people shifts with aging—a discovery that might offer hope in the treatment of speech problems resulting from traumatic brain injury or stroke.

The shift was documented by researchers led by Jerzy Szaflarski, MD, PhD, assistantResearch by Jerzy Szaflarski, MD, PhD, and Scott Holland, PhD, will appear in the February issue of the journal Human Brain Mapping.professor in the Department of Neurology at the University of Cincinnati Academic Health Center, and Scott Holland, PhD, professor in the UC departments of biomedical engineering, pediatrics and radiology. Dr. Holland also heads the Pediatric Brain Imaging Research Program at Cincinnati Children’s Hospital Medical Center.

Their results will be published in the February 2006 edition of the journal Human Brain Mapping.

While the site of language activity in right-handed people is originally the left side of the brain, the researchers report, starting as early as age 5 language gradually becomes a function shared by both sides. Between the ages of about 25 to 67, the site becomes more evenly distributed, until language activity can be measured in both hemispheres simultaneously.

This, the researchers say, may explain why young children who have had a large portion of one side of the brain surgically removed often recover completely.

“This knowledge may give new hope for rehabilitation of brain function in adults after stroke or traumatic brain injuries,” said Dr. Szaflarski. “The fact that language adaptability is seen even in the older people supports the notion that these patients can be rehabilitated and returned to productive life, possibly even after a devastating stroke.

”Scientists have long thought that the hemisphere or side of the brain that controls language and speech is determined before birth. Most people are right-handed and demonstrate more activity during language or speech in the left hemisphere of the brain. In left-handed people language centers are located more symmetrically.

Drs. Szaflarski and Holland studied brain activity in 177 right-handed children and adults aged 5 to 67 at Cincinnati’s University Hospital and Cincinnati Children’s using functional magnetic resonance imaging (fMRI). The technique shows brain activity, in this case language tasks such as reading or speaking, in a specific color.

“Our research revealed that language activity in the brain increases in the dominant hemisphere from age 5 until about 25,” Dr. Szaflarski said, “which may be related to improving linguistic skills and maturation of the central nervous system.

"We observed that the nondominant side of the brain started helping the dominant side during reading or speaking from the age of 25 to 67," Dr. Szaflarski continued. “It’s possible that as cognitive systems began to fail in the dominant side of the brain, the other side or hemisphere needs to compensate. Our study showed that older people have a more balanced capacity for language, with activity on both sides of the brain.

”From around age 5 until about 25, said Dr. Szaflarski, language capacity in right-handers grows stronger in the left hemisphere of the brain. Similarly, fMRI shows increasing brain activity in the right hemisphere of left-handed persons until age 25.

"We were most interested in why this occurs, and the age at which the hemispheric language dominance began to decrease," said Dr. Szaflarski.

Drs. Szaflarski and Holland and their colleagues are also investigating how the brain handles language when it is damaged by a stroke or traumatic brain injury.

In children, Dr. Szaflarski said, the brain seems able to reorganize and shift the work load to the uninjured side. In adults, this doesn’t happen as easily.

With a view to developing better treatment for brain injury in children and adults, the researchers are now trying to learn at what age this transition occurs.

Dr. Szaflarski and Dr. Holland’s research is funded by the National Institutes of Health and the Neuroscience Institute of Cincinnati, a center of excellence in neuroscience specialties at the University of Cincinnati College of Medicine and University Hospital. The Neuroscience Institute, of which Dr. Szaflarski and Dr. Holland are members, is dedicated to patient care, research, education and the development of new medical technologies that may help patients with stroke, epilepsy, multiple sclerosis, trauma, Alzheimer’s disease, Parkinson’s disease and other movement disorders.

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University of Cincinnati Medical Center
Date: 10/5/2005
Sheryl Hilton