Newbie neurons make fear hard to forget

UC BERKELEY (US) — When faced with a fearful situation, newborn neurons are able to produce a blank slate to create a strong imprint of the memory.

The findings have implications for post traumatic stress disorder (PTSD) and other problems caused by faulty regulation of emotional memory.

“We remember emotional events much more strongly than daily experiences, and for a long time we have known that connections between the amygdala and hippocampus help to encode this emotional information,” says Daniela Kaufer, assistant professor of integrative biology at the University of California, Berkeley.

“Our research shows that amygdala input actually pushes the hippocampus to make new neurons from a unique population of neural stem cells. This provides completely new cells that get activated in response to emotional input.”

The research is published in the journal Molecular Psychiatry.

“Many affective disorders involve disordered emotional memories like PTSD, depression, and anxiety. We think that newborn neurons may play a role in creating these emotional memories,” Kaufer says.

The findings follow research showing that the formation of new memories is associated with increased activation of two-week-old newborn nerve cells in the hippocampus that are derived from adult neural stem cells.

Adult stem cells appear to differentiate continually into new nerve cells—nearly 100 each day—yet half of those newborn neurons are slated for death within four weeks after their birth.

If they’re highly activated—such as in learning new complex information—many more of them will survive and presumably help in establishing new memories in the brain.

Researchers already knew that many types of positive and negative experiences, such as exercise and stress, affect the rate of neurogenesis in the hippocampus, but weren’t sure why emotions might affect neurogenesis in the hippocampus, since the brain’s clearinghouse for emotions, the amygdala, is connected to the hippocampus via multiple neural circuits.

To test this, graduate student Elizabeth Kirby, the study’s lead author, focused on the basolateral amygdala, the region of the almond-shaped structure that handles negative emotions, including stress, anxiety, and fear.

Kirby surgically destroyed the basolateral amygdala in rats and discovered that the production of new nerve cells in the hippocampus decreased.

To make sure that the cell damage created when the amygdala was surgically destroyed was not affecting the experiment, the researchers borrowed a gene therapy technique from Robert Sapolsky’s lab at Stanford University to genetically introduce potassium channels into the amygdala, which shut down the activity of the nerve cells without causing injury. This also decreased neurogenesis in the hippocampus.

They next tested the theory that new neurons are especially sensitive to input two weeks after they form. Kirby and Kaufer labeled hippocampal cells created over a three-day period in a group of rats, and then conditioned a fear response in these rats two weeks later.

They then confronted the rats with the same fearful situation or a neutral yet novel context the next day. When they examined the brains, they found that the newborn neurons had been specifically activated by the fearful situation. However, when they destroyed the basolateral amygdala, new neurons were no longer activated in response to the fearful memory.

“The research suggests that newborn neurons play a role not only in the formation of memory, but also in helping to create the emotional context of memory,” Kirby says. It also suggests that the basolateral amygdala drives the ability of new neurons to be part of an emotional memory.

The next step is to see whether other negative stimuli, such as stress and anxiety, similarly cooperate with amygdala activity to alter neurogenesis in the hippocampus.

Researchers from Stanford University and Massachusetts Institute of Technology contributed to the study.

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