The brain translates internal representations of the external world into appropriate innate and adaptive 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 shallow. Moreover, Learned olfactory behaviors are thought to modify innate responses, suggesting that the two pathways intersect. Thus, determined pathways may serve as a substrate upon which experience acts to shape how animals respond to an unpredictable world. We have developed genetic strategies that demonstrate that a stereotyped neural circuit that transmits information form the olfactory bulb to the cortical amygdala is necessary for innate aversive and appetitive behaviors. Moreover, we have employed the promoter of the activity-dependent gene, arc, to express the photosensitive ion channel, channelrhodopsin, in neurons of the cortical amygdala activated by odors that elicit innate behaviors. Optical activation of these neurons leads to appropriate behaviors that recapitulate the responses to innate odors. Thus, we have revealed that neurons in the cortical amygdala are both necessary and sufficient to elicit innate olfactory-driven behavioral responses. The goal of this proposal is to further define pathways for innate behaviors and identify the underlying mechanisms for modulation of behavior by experience. We have demonstrated that the cortical amygdala is a substrate for innate pathways. Moreover, piriform cortex, a structure implicated in olfactory learning, has a strong projection to cortical amgydala. We propose a model whereby the convergence of processed associational input from piriform cortex and direct bulbar input to cortical amygdala provides a circuit for experience-dependent olfactory behaviors. We will employ a combination of behavioral experiments, molecular genetics and endoscopic imaging of neuronal activity to ask three principal questions: 1) How is the cortical amygdala organized to elicit different behaviors? 2) Is the pathway from piriform cortex to the cortical amygdala required for experience-dependent modulation of innate behaviors? 3) Does the polysynaptic circuit from piriform cortex to cortical amygdala play a role in adaptive responses to novel odors? The training plan, under the primary mentorship of Dr. Richard Axel at Columbia University, provides a comprehensive strategy for acquiring the necessary experimental and professional skills within an exemplary and collaborative neuroscience environment. An experienced team of collaborators will provide training in skills critical for my short- and long-term success, including in vivo imaging of neural activity and mapping of neural circuits. Focused mentor guidance, alongside frequent data presentation, will provide the communication and leadership skills vital for my transition to independence. In the long-term, this support will equip me to lead a laboratory that merges molecular and systems approaches to explore how internal states and past experiences affect choice behaviors.
Investigating the neural circuits underlying sensory perception provides a critical window into understanding how the brain functions normally and in disease. Using the sophisticated molecular genetic tools available for mice, this proposal will delineate the neural substrates for olfactory behaviors and identify underlying mechanisms for modulation of behavior through experience. 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.
