ABSTRACT Short-term memory is an essential component of cognition. Here, we will investigate an ethologically relevant form of short-term memory that guides navigation behavior: memory of odor concentration across sniffs. This intersniff memory has been shown to guide olfactory search in studies of freely moving animals, but the stimuli in these experiments are hard to control and measure. To better control concentration fluctuation, we have developed a system for presenting stimuli that rapidly change concentration to head- fixed mice. Using this system, we have revealed that neurons of the olfactory bulb have intersniff memory, with responses that depend on stimulation in previous sniffs. Here, we will investigate the duration, resolution, and cellular basis of intersniff memory representations using electrophysiology, 2-photon imaging, and high-resolution behavioral analysis. Will intersniff memory codes inferred from head-fixed experiments generalize to natural behavior? To answer this question, we have established an unrestrained olfactory navigation assay. Mice learn this task rapidly, and solve the task by following odor concentration changes. We have found that mice execute a repertoire of three-dimensional movements that are precisely synchronized to the sniff cycle. Importantly, these behavioral dynamics are only revealed when an animal is able to move naturally in the environment. How do these movements impact intersniff memory representations? Our behavioral task gives us an unprecedented opportunity to test receptive field models derived from controlled simple stimulation in the context of naturalistic stimulation and movement. For a given mouse, we will first record in head-fixed and determine intersniff memory coding in that condition. We will then test the same neurons in the same mouse in our behavioral task. How well can the head-fixed coding rules predict activity in the freely-moving condition? By defining the neural representation of ethologically relevant odor dynamics, our work will advance a general understanding of how the brain implements short-term memory for input that changes through time, which is essential to guide successful behavior.

PROJECT NARRATIVE As sensory input changes through time, the sense of smell must track and represent these changes using a form of short-term memory. We will investigate how the mouse processes time-varying odor stimuli, and how neural circuits transform inputs into useful patterns of activity. Gaining insight may lead to better strategies for sensory prostheses and treating sensory deficits.