The key to understanding this delicate mechanism, Anderson says, was in uncovering "markers"genes that would identify and allow for the scientists to discriminate between the different neuronal cell types in the amygdala. Anderson's group, led by postdoctoral fellow Wulf Haubensak, found its marker in a gene that encodes an enzyme known as protein kinase C-delta (PKCδ). PKCδ is expressed in about half the neurons within a subdivision of the amygdala's central nucleus, the part of the amygdala that controls fear output.
Along with fellow postdocs Prabhat Kunwar and Haijiang Cai, Haubensak was able to fluorescently tag neurons in which the protein kinase is expressed; this allowed the researchers to map the connections of these neurons, as well as to monitor and manipulate their electrical activity.
The studies, Anderson says, "revealed that PKCδ+ neurons form one end of a seesaw, by making connections with another population of neurons in the central nucleus that do not express the enzyme, which are called PKCδ− neurons." They also showed that the kinase-positive neurons inhibit outflow from the amygdalaproving that they act as the end of the seesaw that rests on the garden hose.
Still, a key question remained: What happens to the seesaw during exposure to a fear-eliciting signal? Anderson and his colleagues hypothesized that the fear signal would push down on the opposite end of the seesaw from the one formed by the PKCδ+ neurons, removing the crimp from the garden hose and allowing the fear signal to flow. But how to test this idea?
Enter neurophysiologist Andreas Lthi and his student Stephane Ciocchi, from the Friedrich Miescher Institute in Basel, Switzerland. In work done independently from that of the Anderson lab, Lthi and Ciocchi had managed to record electrical signals from the amyg
|Contact: Jon Weiner|
California Institute of Technology