The focus of this research program is on the amygdala, a forebrain structure necessary for processing aversive and rewarding stimuli and orchestrating a wide array of behaviors associated with emotions and motivation. This brain structure which is characterized by a high degree of cellular heterogeneity and interconnectivity, is incompletely understood. Despite its importance, we do not have a circuit diagram that would depict the flow of information during the various emotional behaviors. The research program will provide new insights into the principles of assembly and function of this evolutionarily conserved brain structure. The successful completion of this project will considerably benefit society since the amygdala is implicated in a wide range of disease states, including anxiety disorders, addiction, eating disorders, and autism. Principles identified in rodents using this approach have the potential to be directly relevant to humans, because of the well-conserved anatomy of the amygdala.
The overall objective of this proposal is to genetically redesign specific amygdala circuits during mouse development in a predictable fashion, and to test the consequences for innate and learned behavior. We aim to demonstrate that targeted mis-expression of connectivity signals can alter specific neural circuits and communications between circuit components along measurable hypotheses. Activation of such an artificial circuit, by either natural stimuli or optogenetics, is likely to produce a set of behavioral outcomes that will reveal general connectivity rules, the capacity for behavioral plasticity, and possible functional redundancies between circuits. Anatomical and physiological dissection of the redesigned circuit will reveal to what extent the circuit is genetically hardwired or whether incoming information (afferents) instructs the target neurons to produce their correct output responses.
