Understanding functional transformations carried out by the bulb

Project Summary/Abstract Compromised olfactory function is associated with the aging process, as well as a number of human diseases. Our incomplete understanding of the brain makes it challenging to comprehend the mechanisms that underlie these sensory deficits and other psychiatric disorders. Understanding how sensory information is encoded and transformed by neural circuits will help define the basic mechanisms that underlie these challenges. For many animals, smell is critical for recognizing and locating food, mates and dangers. Odor recognition requires the identification of a specific smell that can vary in intensity, while localization involves detecting a concentration profile that varies in time and space. Both processes must be carried out while the stimulus is embedded in a complex chemical context. This requires that the olfactory system recognize and maintain a concentration- invariant representation of the odor, while detecting its changing concentration gradient and segmenting its percept from other chemical stimuli present in the environment. Understanding how the brain carries out these processes is key to understanding perceptual stability. The goal of this proposal is to define the neural circuits that support odor recognition and the ability to adjust sensitivity to complex olfactory scenes in vivo. First, we will define how changes in odor concentration are encoded and transformed across the olfactory bulb circuit. Next, we will examine how different concentrations or durations of odor exposure impact olfactory bulb responses to future odor stimulation. We will then test the hypothesis that olfactory bulb adaptation underlies dynamic range adjustments involved in maintaining sensitivity in different odor backgrounds. This proposal will answer these questions using an imaging approach to measure the neural activity from the olfactory receptor neuron input, and the mitral/tufted cell output that innervate olfactory bulb glomeruli. We will pair this strategy with a mechanistic toolkit to dissect the underlying mechanisms that drive functional transformations in the bulb. The impact of this proposal will be to generate a comprehensive mechanistic description of how two perceptual functions are carried out by the olfactory bulb, which are the critical first steps that will ultimately link physiology with naturalistic behavior.