News Release

How safety feels good

Peer-Reviewed Publication

Cell Press

Much research has been done on how "fear-conditioning" affects brain circuitry, but what about the flip side: "safety conditioning?" Now, researchers led by Michael T. Rogan and Eric R. Kandel of Columbia University Medical Center have discovered in mice how the brain responds to external stimuli that signal safety. Their findings, say the researchers, could aid in treating psychiatric disorders involving a feeling of loss of safety, as well as understanding why some people respond more resiliently to trauma than others.

In their experiments, the scientists first safety-conditioned mice by teaching them to associate a series of beeps with the absence of a mildly uncomfortable foot shock. They found that the beeps reduced the classic "freeze" defensive response in the trained mice. They also found that when the safety-conditioned mice, compared to control mice, heard the beeps, they would increase adventurous exploration of an open space--abandoning their normal, protective, wall-hugging behavior. The mice showed the same adventurous behavior when exposed to an instinctive safety signal--dimmed light--indicating that the same neural response mechanisms were at work, said the researchers.

When the safety-conditioned mice were given the choice of two rooms--one in which their entry triggered the safety signal--they overwhelmingly chose the "safety" room.

Electrophysiological studies of the animals' brains revealed that the safety tones depressed activity in a region of the amygdala--the brain structure that processes emotions and that is activated in fear responses. In contrast, fear-conditioned animals showed an increased activity in that region. The brain measurements also revealed that the safety signal increased activity in the region known to be involved in positive affect, euphoric responses, and reward. Fear-conditioning had no affect on that region.

"These findings support the idea that learning about safety and learning about danger are related but independent processes," wrote the researchers. "Our data suggest a partial overlap of these two processes for an auditory [safety signal], extending from sensory processing through early amygdala processing."

The researchers concluded that "It will be interesting to examine the distinction between the positive response to safety and responses to stimuli traditionally understood to have hedonic value, such as food and sexual activity. The neural and molecular genetic substrates of these mechanisms are likely to provide new targets for the treatment of a variety of psychiatric disorders involving anxiety, mania, anhedonia, and addiction, and a greater understanding of highly adaptive psychological characteristics such as resilience."

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The researchers included Michael T. Rogan, Kam Sam Leon, and David L. Perez of Columbia University Medical Center; and Eric R. Kandel of Columbia University Medical Center, Kavli Institute for Brain Science, and Howard Hughes Medical Institute. This work was supported by Kavli Institute for Brain Science, Howard Hughes Medical Institute, and grants from the National Institutes of Health. Eric R. Kandel is one of four founders of Memory Pharmaceuticals and is Chairman of its Scientific Advisory Board. Memory Pharmaceuticals is concerned with developing drugs for age-related memory loss. Some of these drugs are also potentially useful in depression and schizophrenia.

Publishing in Neuron, Volume 46, Number 2, April 21, 2005, pages 309–320. http://www.neuron.org


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