Sniff-synchronized, gradient-guided olfactory search by freely moving mice.

For many organisms, searching for relevant targets such as food or mates entails active, strategic sampling of the environment. Finding odorous targets may be the most ancient search problem that motile organisms evolved to solve. While chemosensory navigation has been well characterized in microorganisms and invertebrates, spatial olfaction in vertebrates is poorly understood. We have established an olfactory search assay in which freely moving mice navigate noisy concentration gradients of airborne odor. Mice solve this task using concentration gradient cues and do not require stereo olfaction for performance. During task performance, respiration and nose movement are synchronized with tens of milliseconds precision. This synchrony is present during trials and largely absent during inter-trial intervals, suggesting that sniff-synchronized nose movement is a strategic behavioral state rather than simply a constant accompaniment to fast breathing. To reveal the spatiotemporal structure of these active sensing movements, we used machine learning methods to parse motion trajectories into elementary movement motifs. Motifs fall into two clusters, which correspond to investigation and approach states. Investigation motifs lock precisely to sniffing, such that the individual motifs preferentially occur at specific phases of the sniff cycle. The allocentric structure of investigation and approach indicates an advantage to sampling both sides of the sharpest part of the odor gradient, consistent with a serial-sniff strategy for gradient sensing. This work clarifies sensorimotor strategies for mouse olfactory search and guides ongoing work into the underlying neural mechanisms

The Ethics of Developing New Treatments: A Case tudy of the West African Ebola Outbreak and the Use of Randomized Control Trials

Submitted to the Undergraduate Library Research Award scholarship competition: (2019). 20 p.The 2014-2015 Ebola epidemic was the most devastating Ebola outbreak in history which killed over 10,000 people. During the outbreak, the WHO led efforts to design the best method to test the potential treatments quickly. Randomized controlled trials (RCTs) were proposed as the best method, although many experts opposed their use, deeming them inappropriate in the context of an epidemic. Despite the long debates, RCTs were used to test the available treatments. This paper presents the arguments given in support of and against RCTs, and analyzes a few RCTs conducted to answer the following question: “were RCTs effective at helping researchers fight the epidemic?” This paper argues that RCTs were not the best approach for two reasons: the principle of equipoise requires that the available treatments be provided to patients; if RCTs were to be used, they should have begun earlier to ensure the validity of the findings

Glomerular Signals Underlying Olfactory Navigation

38 pagesThe olfactory system is the least-studied sense, although it plays key roles in different aspects of our existence. Our lab and others have examined the behavioral structure of olfactory navigation and have found that mice use a combination of serial and stereo cues to locate the source of an odor. Our next goal is to compare sampling movements directly against sensory input in freely moving mice in order to establish a correlation between sensory input and mouse behavior. Most imaging studies have been conducted on restrained mice, which allows for better control. However, animals behave differently when restrained, and specific behavioral dynamics can only be studied when the animal can move naturally in the environment. The first step in this goal, which is the topic of this project, is to successfully express fluorescence indicators in the olfactory bulb and to detect this expression using our imaging apparatus. For this purpose, we have been troubleshooting the surgical and imaging techniques necessary to begin our experiments. To achieve the expression of our fluorescence sensor GCaMP, we either injected a virus encoding the fluorescence protein into mice brains or engineered mice to encode the sensor gene in their genome. Histology revealed that we successfully expressed GCaMP in some mice, while we could only observe background fluorescence in others. This could result from the frying of the bulb due to continuous expression of the protein or degradation of the virus. Despite the difficulty of the surgeries, we could visualize activity in the glomeruli of live mice with the two-photon microscope, although our success rate remains low. We are continuously adjusting our protocol to improve our techniques, so we can move on to the next stage of our project

Imaging Glomerular Signaling of Unrestrained Olfactory Search in mice

Project files include 1 page pdf.Olfaction is vital for many crucial animal behaviors such as social interaction, avoiding predators, and locating food. Our goal is to understand how an animal navigates toward the source of an odor. However, little is known about how odors are coded to inform olfactory search behavior. Air turbulence can cause odor distributions to be highly variable and unpredictable. Although we have previously characterized specific behavioral patterns in turbulent odor plumes, little is known about how odors are translated into movements. Our goal is to capture and understand the sensory input that informs these previously observed behaviors. We do this by injecting iGluSnFR, a fluorescent glutamate reporter, into the mitral cell layer of the olfactory bulb. This reporter tells us how glutamate released from olfactory sensory neuron terminals influences activity of mitral cells. iGluSnFR's fast kinetics allows us to observe and measure glutamate levels as the mouse performs olfactory navigation. By revealing activity in olfactory sensory neurons during olfactory navigation, this technique can tell us how odor informs the mouse's brain during active sampling. Following the development of this technique, we will image from iGluSnFR mice performing our olfactory search task to determine the neural computation that connects movement and sensation. Understanding how mice translate odor into behavior will inform our understanding of active sensory sampling behaviors in humans.Alden Schola