Working with Ressler, postdoctoral associate Dennis Choi and colleagues took advantage of a strain of genetically engineered mice that lack the BDNF gene in certain parts of the brain. These include the prelimbic cortex but exclude the amygdala and other regions such as the hippocampus.
If mice are electrically shocked just after they hear a certain tone, they gradually learn to fear that tone, and they show that fear by freezing. The BDNF-altered mice could run around and respond to shocks just as well, and could still learn to fear tones "in the moment."
However, they seemed to have trouble retaining fear memories as time passed. After learning to fear the tone, the altered mice didn't freeze as much, compared to normal mice, one hour or a day later. Using a different approach, the researchers also found that mice injected with a virus that eliminates the BDNF gene in the prelimbic cortex display similar characteristics.
"This work is important for extending our understanding of how BDNF is important for neuronal plasticity, learning and memory," Ressler says. "Together with our previous work, these data suggest that preventing neural plasticity in very precise, but critical brain regions, can have vastly different effects on emotional memory.
"It is becoming increasingly clear that these prefrontal cortex regions are functionally associated with regions of the brain known for a long time to be involved in emotion, such as the amygdala and hippocampus," he adds. "Understanding the molecular and cellular mechanisms of these connections in rodent models will provide scientists a better understanding of how these similar areas are functioning in humans."
A related paper in PNAS from Keqiang Ye, PhD, associate professor of pathology and laboratory medicine at Emory, and colleagues describes a family of compounds that can mimic BDNF.
|Contact: Holly Korschun|