Functional anatomy of neural circuits regulating fear and extinction

When an animal experiences fear in the presence of threatening stimuli, it can help it to survive in an adverse environment. However, exaggerated fear may result in anxiety disorders, which impairs normal functioning. Although fear can be reduced or even removed by repeated presentations of fear-eliciting stimuli in a safe situation, such extinction of fear is neither permanent nor complete. Fear can renew because extinction does not erase existing memories, but rather creates new ones. It has been suspected that there are distinct neuronal circuits underlying fear extinction and renewal. In our study, we showed that in the lateral part of the amygdala (a brain structure responsible for emotions), there are two groups of nerve cells independently activated by high or low levels of fear. These cells are differentially connected with the prefrontal cortex and hippocampus, structures informing the animal when and where it previously encountered certain situation. To study functional anatomical connections, we used a newly generated transgenic rat, in which one can actually see activated neurons and applied a method of anatomical pathways tracing with fluorescently labeled markers. Identification of two distinct neuronal circuits activated by low or high levels of fear is the first step to explore the possibility of a very specific improvement of fear extinction mechanisms (at the level of individual cells). The method of functional anatomical tracing developed in our study can also be used to investigate neuronal circuits underlying behaviors other than fear.

28 January 2013