2017 |
Shusterman, Roman (co-PI) Smear, Matthew C |
R56Activity Code Description: To provide limited interim research support based on the merit of a pending R01 application while applicant gathers additional data to revise a new or competing renewal application. This grant will underwrite highly meritorious applications that if given the opportunity to revise their application could meet IC recommended standards and would be missed opportunities if not funded. Interim funded ends when the applicant succeeds in obtaining an R01 or other competing award built on the R56 grant. These awards are not renewable. |
Concentration Change Representation in the Olfactory Bulb
PROJECT SUMMARY / ABSTRACT Locating objects of interest in space is a vital aspect of sensation. In most mammals, olfaction plays an important role in localization, yet the neural basis of this ability remains poorly understood. As animals move toward an odor source, the odor concentration changes from sniff to sniff. These concentration changes have been shown to guide odor source localization in studies of freely moving animals. Yet studies in freely moving animals do not allow sufficient stimulus control for precise study of olfactory neuronal or behavioral responses. We have developed a system for presenting stimuli that rapidly change concentration to head- fixed mice. In this proposal, we will use this system to mimic odor concentration fluctuation during source localization and to study how the mouse olfactory bulb represents stimuli that change concentration from sniff to sniff. In preliminary experiments, we have found that a subset of neurons in the olfactory bulb is sensitive to concentration changes, modulating their activity when the odor concentration changes across sniffs. In Specific Aim 1, we will investigate the novel response properties of these neurons in electrophysiological recordings. In Specific Aim 2, we will take an optogenetic approach to test whether these concentration change sensitive neurons are a functional cell type. Finally, in Specific Aim 3, we will record in animals performing a precise psychophysical task in which they report detection of concentration changes. We will ask whether activity in concentration change sensitive neurons can predict the animal's perceptual report. By defining the neural representation of ethologically relevant odor dynamics, our work will advance a general understanding of how the brain operates with input that changes through time, which is essential to guide successful behavior.
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2017 — 2018 |
Shusterman, Roman Smear, Matthew C |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Impact of Cortical Feedback On Odor Concentration Change Coding
ABSTRACT Top-down feedback connections between ?higher? and ?lower? brain areas are quite common, but their functional role remains a mystery. This general principle applies to the olfactory system, in which the olfactory bulb receives dense feedback innervation from its cortical targets. Here, we propose techniques with which feedback neurons can be targeted by a viral/transgenic intersectional strategy in mice. Using this strategy, we will identify feedback neurons during electrophysiological recordings by optogenetic tagging. In addition, we will exclusively silence the feedback axons in olfactory bulb, in a way that will not affect the feedforward connections of these neurons. In the timeframe of this proposal, we will apply these techniques to determine the role of one olfactory cortical area, the anterior olfactory nucleus, in one olfactory computation: sensing odor concentration changes over time. This computation is very important to a mouse, because sensing concentration changes over time can enable a mouse to locate odor sources. We have recently reported that a substantial subset of neurons in olfactory bulb explicitly represent concentration changes. Because inhalation parses odor input into discrete, intermittent samples, computing concentration change requires a memory of stimulation during past inhalations. We hypothesize that anterior olfactory nucleus provides this putative memory signal via its feedback projection. This hypothesis predicts that responses of feedback neurons will represent the previous sniff's odor concentration, even after the stimulus has ceased. In Aim 1 of this proposal, we will test this prediction by delivering dynamic concentration stimuli to awake mice, while we record electrophysiologically from neuronal ensembles in which we can use optogenetic tagging to distinguish feedback from non-feedback neurons. Another prediction of our hypothesis is that feedback signals are essential to computing concentration changes. In Aim 2, we will test for a causal role of feedback in this computation, by silencing feedback axons in the olfactory bulb while we record the responses of olfactory bulb neurons to odor concentration dynamics. With the proposed experiments, we will determine how and whether anterior olfactory nucleus participates in concentration change sensing. In the longer term, the methods we propose here will enable us to determine the role of feedback neurons in other olfactory areas, such as piriform or lateral entorhinal cortices, in sensing concentration changes, as well as other relevant olfactory computations. Importantly, the optogenetic silencing strategy we propose is compatible with behavioral experiments, because we will selectively silence feedback axons without affecting activity in the neurons' cell bodies. Thus, feedback can be dissected from feedforward signals, which will make experimental results easier to interpret. Ultimately, the techniques established here will facilitate our big picture goal of elucidating the role of top-down feedback in neuronal computation.
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