CAREER:Investigating how internal states, learning, and memory shape olfactory coding

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A central principle of neuroscience is that sensory stimuli are represented as patterns of neuronal activity that ultimately give rise to behaviors. Interestingly, even when a stimulus is fixed, such as the odor from a food source, behavioral responses can be diverse, almost necessarily influenced by an assortment of factors ranging from the animal's internal state to memory. These collectively determine which one of many possible behaviors will be selected. In the odor example, the decision to approach the food source may be influenced by the degree of satiety vs. hunger, the valence of the odor (were these odors "good" the last time they were encountered?), any memory the animal might have about lurking predators (a calculation of risk versus reward), or an efficient strategy for search the animal has learned. These are examples of the array of information that gets integrated to select "the correct" behavior for survival in a complex world. Recent evidence suggests that control points for behavioral flexibility can happen as early as the level at which sensory information is first processed. In this model, feedback or top-down projections from higher processing areas directly alter patterns of neuronal firing in primary sensory regions. As a result, these feedback projections affect behavior by manipulating how stimuli are encoded in primary sensory regions. Thus, animals respond differently because they encode the world differently. This project uses an array of experimental and computational tools to advance understanding of this top-down modulation of sensory information. The project also includes the implementation of a computational neuroscience course for senior undergraduate and graduate students, and of a Virtual Reality program that enables students, including K-12 and local community college students, to visualize dynamics of neural networks.This project investigates central modulation of peripheral sensory processing as a mechanism of influencing behavioral endpoints. To study this question, two things are required: A feedback circuit in the brain that 1) encodes for complex representations including memory, fear, and anxiety for instance, and 2) targets primary sensory regions. Recent studies have identified a direct feedback connection from the ventral CA1 (vCA1) region of the hippocampus (that encodes fear, internal state, social information, and learning) to the main olfactory bulb 1 synapse from where odors are first detected in the mouse. This connection provides a compact experimental system with which to interrogate how internal states and/or learning and memory influence the neuronal representations of sensory stimuli at the earliest stages. By using this circuit, this project: (1) examines the patterns of connectivity between vCA1, the olfactory bulb and other known target regions to identify the networks involved in this feedback control; and (2) determines how vCA1 feedback reshapes the activity of neurons in the main olfactory bulb in response to odors. For the first aim, newly developed retrograde tracers are used to label connections from vCA1 to the bulb in tandem with automated whole brain reconstruction methods to identifying the structural logic of feedback circuits. For the second aim, optogenetic technology is used to control vCA1 activity while recording the activity of large populations of neurons in the main olfactory bulb, and thus to identify the physiological effects of feedback projections and the role feedback plays in encoding information about odor identity and concentration. This project is co-funded by the Mathematical Biology program in the Division of Mathematical Sciences and the Physics of Living Systems program in the Division of Physics of the Directorate for Mathematical and Physical Sciences.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.