Molecular genetic approach to emotional states

DESCRIPTION: The goal of this project is to identify some of the neural circuits and molecular substrates that underlie emotional states. Serotonin is a neuromodulator that has been implicated in normal mood control as well as in a number of mood disorders such as anxiety, depression and aggressiveness. To model such disorders the investigators have introduced mutations in various components of the serotonergic system. In particular, they have generated knockout mice that lack either the 5-HT1A or the 5-HT1B receptor. These mutant mice display a panoply of contrasting phenotypes. While the 5HT1B knockout mice appear to be more aggressive and less anxious than the wild types, the 5-HT1A knockout mice appear to be less aggressive and more anxious than wild types. In the present project the investigators propose to take advantage of these two mouse models to identify the neural circuits that are responsible for their opposite emotional states. They will characterize the molecular adaptations that might be responsible for variations in anxiety and aggressive behavior in these two knockout strains. Experiments will be conducted to address three specific aims. The first specific aim will be to identify the neural circuits that are differentially activated in 5-HT1A and 5-HT1B knockout mice. In a second specific aim, they will identify the neural circuits that are responsible for the changes in anxiety and aggressiveness found in 5-HT1A and 5-HT1B knockout mice and in a final specific aim they will identify the molecular adaptations that are associated with variable levels of anxiety and aggressiveness in 5-HT receptor knockout mice.