The brain translates internal representations of the external world into appropriate behaviors. Elucidation of how sensory information is propagated through hierarchical systems is an important step towards understanding how the brain instructs behavior. The sense of smell is a tractable model because the pathways from the nose to associational cortex and emotional structures in the amygdala are relatively concise. Innate behaviors are stereotypical between animals and likely result from genetically determined and conserved circuits, making them a tractable model. Our past work has revealed circuits in the cortical amygdala (plCoA) that mediate innate attraction and aversion to odor. Understanding how the sense organ is wired to the brain to produce behaviors of different valence is an important biological problem and may provide insight into emotional responses to sensory stimulation. We have combined anatomical tracing with functional manipulations to reveal two outputs of the plCoA, the nucleus accumbens (NAc) and medial amygdala (MeA), that are capable of eliciting approach and avoidance responses, respectively. Further, we have evidence to suggest that there is a topographic organization to the plCoA circuitry. Thus, we hypothesize that the plCoA contains topographically organized labeled lines to impart valence on odor-evoked behaviors. The goal of this proposal is decipher the plCoA circuitry and its connections to the NAc and MeA. We have demonstrated that the cortical amygdala projections to NAc and MeA are able to generate approach and avoidance behaviors. Moreover, these projection neurons appear to be distinct from each other. We propose a model whereby the plCoA sends projections to the NAc to signal positive valence, and to medial amygdala to signal aversion. We will employ a combination of behavioral experiments, viral tracing, genetics and endoscopic imaging of neuronal activity to answer three fundamental questions: 1) Do the plCoA projections to NAc and MeA mediate odor-evoked behaviors? 2) How are the plCoA projection neurons anatomically organized? 3) Do these projection neurons and their downstream targets exhibit odor tuning for valence? The answers to these questions will fill a knowledge gab about the representation of odor in the innate pathway and extend this pathway deeper into the brain towards behavioral output.
Investigating the neural circuits underlying sensory perception provides a critical window into understanding how the brain functions normally and in disease. Using the sophisticated genetic tools and advanced imaging approaches, this proposal will dissect the mouse brain circuits that impart behavioral valence on odor stimuli. Our work seeks to elucidate fundamental principles in sensory neurobiology that are generally applicable to neuronal processing, with the long-term hope that these principles will provide insight into neurological disorders of sensory systems. !
