2006 — 2008 |
Verhagen, Justus V |
R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Sniffing and Optical Imaging of Olfactory Bulb Responses @ John B. Pierce Laboratory, Inc.
[unreadable] DESCRIPTION (provided by applicant): The goal of this project is to understand how odorant representations by populations of olfactory receptor neurons at the level of their input to the olfactory bulb are modified by sniffing in awake rats. While population responses of the olfactory bulb and sniffing behavior have been explored to some degree in separation, and it has become clear that sniffing could have a major impact on odorant encoding, it is entirely unknown how sniffing actually affects odor encoding in the olfactory system. The transformation of odorant information from the spatially roughly organized olfactory epithelium to the spatially highly organized olfactory bulb, allowed by highly specific convergence of olfactory receptor neurons onto glomeruli, is a critical step in this encoding process. It is clear that airflow can modulate where odorants sorb to the olfactory epithelium, and it is clear that the spatial organization of receptor neurons is by no means random. The input of the olfactory bulb, which acts like a window on the olfactory receptor repertoire of odorants, is hence likely to be affected by sniffing. If so, this undoubtedly has major affects on higher order processing as well. Indeed, several important hypotheses rely on the assumption that sniffing is invariable. This study will focus on the impact of sniffing of odorants on the coding and processing of information about odors at this first level of the olfactory pathway by selectively imaging activity in olfactory receptor neuron terminals while rats are performing an olfactory discrimination task and sniffing activity is measured. Specifically, this study will: 1) determine to what extent sniffing modulates the neural odormaps in the olfactory bulb; 2) determine whether the phenomenon of enhanced sniffing in response to lower odorant concentrations leads to concentration-invariance of input odormaps to the bulb. Together, these experiments will constitute a significant step towards understanding how odor quality - encoding at a specific level of the olfactory pathway is affected by the ubiquitous and natural behavior of sniffing in rats. Understanding the basic functions of the olfactory system can potentially lead to improved diagnosis and treatment of diseases of the nervous system. [unreadable] [unreadable] [unreadable]
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0.988 |
2009 — 2012 |
Verhagen, Justus V |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Multimodal Flavor Integration and Retronasal Olfaction in the Rat @ John B. Pierce Laboratory, Inc.
Description (provided by applicant): How multimodal stimuli become integrated is a fundamental question in neuroscience. This question is particularly relevant to flavor perception, in which simultaneous stimulation of touch, temperature, taste and olfaction invariably occurs during ingestion. Functional imaging studies in humans have provided important insights into the neural bases of multimodal flavor integration, yet cannot address issues requiring higher resolution or experimental manipulation of neural activity or of flavor experience. To address these limitations, the goal of the present project is to establish a rat model for investigating the neural mechanisms of flavor integration. To determine whether retronasal olfaction occurs in rats as it does in humans, a first study will employ optical calcium imaging to measure spatio-temporal patterns evoked in the olfactory bulb by various behaviors associated with the oral ingestion of odorants by awake rats. The perceptual similarities between retro- and orthonasal odorants will simultaneously be investigated. To determine whether flavor integration occurs perceptually in rats, a second study will investigate whether conditioned odor aversions generalize to tastants, and whether conditioned taste aversions generalize to odorants. It will also be examined whether prior odor-taste pair experience is necessary for generalization to occur and whether the specificity of the generalization follows this learned taste-odor quality congruence. A separate study will investigate the flavor experience-dependence of the potentiation of an odor aversion by taste and of a taste aversion by odor. To determine whether multi-sensory integration occurs in the olfactory bulb, the third study will evaluate whether and how oral stimuli can modulate odor responses in the optically-imaged olfactory bulb of awake and acute rats. The importance of both stimulus quality congruence, as established by modulating flavor experience, and temporal congruence for flavor integration will also be assessed. Together these studies are intended to provide fundamentally new knowledge about the neural mechanisms of flavor perception using a rat model. PUBLIC HEALTH RELEVANCE: This project investigates the neural basis of flavor perception. Because flavor plays a central role in motivating food intake, research on the neural mechanisms of flavor perception is essential for understanding the sensory factors that contribute to eating-related disorders such as obesity, diabetes and cardiovascular disease.
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0.988 |
2011 — 2015 |
Verhagen, Justus V |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Bulbar Maps to Retronasal Smell by Optical Calcium Imaging and Fmri in Acute Rat @ John B. Pierce Laboratory, Inc.
DESCRIPTION (provided by applicant): The flavor of a food is comprised of information from multiple sensory modalities. One major modality is the sense of smell. During food ingestion it is the retronasal smell, not the orthonasal route that informs about the chemical make-up of food. Functional imaging studies in humans have provided important insights into the neural bases of multimodal flavor integration, and provided support for the hypothesis that brain processing of ortho- and retronasal smell differs. Yet, the upstream olfactory bulbs of humans are not accessible to fMRI. Limited evidence suggests that the neural representations of odorants at the first stage of processing olfactory information, the olfactory bulb (OB), differ between these two modes of smell. However, to date no study has directly investigated odor maps to retronasal smell. Virtually every study on bulbar maps in vertebrates is on orthonasal smell only. In addition to the retronasal maps remaining unknown, it also remains unclear how representations are transformed across the first olfactory synapse in the glomerulus. To date no study has unambiguously compared presynaptic and postsynaptic responses in OB. More generally, it remains unclear how optically imaged neural calcium responses relate to those reported by peri/post-synaptic fMRI BOLD. To fill in these gaps in our knowledge of flavor encoding and transformation in the OB and its translation to human fMRI studies, we propose to image retronasal and orthonasal odor maps in the anesthetized rat. We propose two comparative sets of studies. In the first Aim, we will image only the dorsal OB at glomerular resolution to only orthonasal responses by using innovative micro-fMRI with phased coil arrays and by using presynaptic calcium dyes, to investigate their neurobiological relation, in the same animal. In the second Aim we will image responses to both orthonasal and retronasal odors across the entire OB with fMRI, and the dorsal OB optical calcium imaging, in the same animal. Whereas fMRI has access to the entire OB, optical imaging of the dorsal OB has a higher spatial and temporal resolution. For both complementary approaches the methods will be essentially the same, uniquely allowing us to compare the odor maps derived by both techniques. To further understand the effects of parameters relevant to olfaction, we will image responses to an array of stimuli with a large span of lipophilicity. We will furthermore investigate the effects of odor flow rate and odor concentration on the odor maps of the OB. Together these studies are intended to provide fundamentally new knowledge about the neural mechanisms of retronasal smell, and of bulbar neural transformations using a rat model and these studies are a first step toward translation of rodent functional imaging to human olfactory fMRI research. PUBLIC HEALTH RELEVANCE: This project investigates the neural encoding of retronasal smell. Retronasal smell forms an obligatory and important aspect of the flavor of food. Because flavor plays a central role in motivating food intake, research on the neural mechanisms of flavor perception is essential for understanding the sensory factors that contribute to eating-related disorders such as obesity, diabetes and cardiovascular disease.
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0.988 |
2015 — 2018 |
Verhagen, Justus |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Collaborative Research: Olfactory Navigation: Dynamic Computing in the Natural Environment @ John B. Pierce Laboratory, Incorporated
This project was developed at an NSF Ideas Lab on "Cracking the Olfactory Code" and is jointly funded by the Physics of Living Systems program in the Physics Division, the Mathematical Biology program in the Division of Mathematical Sciences, the Chemistry of Life Processes program in the Chemistry Division, and the Neural Systems Cluster in the Division of Integrative Organismal Systems. The project is a synergistic combination of laboratory experiments and computer modeling that will lead to better understanding of how animals use the sense of smell to navigate in the real world. Almost universally, from flies to mice to dogs, animals use odors to find critical resources, such as food, shelter, and mates. To date, no engineered device can replicate this function and understanding the code used by the brain will lead to many novel applications. Cracking codes, from neural codes to the Enigma code of WWII, is aided by a deep understanding of the content of messages that are being transmitted and how they will be used by their intended receivers. To crack the olfactory code, the team will focus on how odors move in landscapes, how animals extract spatial and temporal cues from odor landscapes, and how they use movement for enhancing these cues while progressing towards their targets. The proposed work encompasses physical measurement of odor plumes, behavioral measurement of animals' paths through olfactory environments, electrophysiological and optical measurement of neural activity during olfactory navigation, perturbations of the environment via virtual reality and of neuronal hardware via genetics, and multilevel mathematical modeling. The PIs will teach and work with undergraduate, graduate and postdoctoral students and especially recruit students from underrepresented groups in science. The project's results may lead to improved methods for the detection of explosives, new olfactory robots to replace trained animals, and new theoretically-grounded advances in robotic control. The project will inform the development of technologies that interfere with the ability of flying insects (including disease vectors and crop pests) to locate their odor target, thus opening a new door for developing 'green' technologies to solve problems that are of global economic and humanitarian importance.
This proposal is a synergistic combination of laboratory experiments and computational modeling that will probe how animals use olfaction to navigate in their environment. Specifically, this effort seeks to solve the difficult problem of olfactory navigation through the following aims: (i) Generate and quantify standardized, naturalistic odor environments that can be used to perform empirical and theoretical tests of navigation strategies; (ii) Determine phenomenological algorithms for odor-guided navigation through behavioral experiments in diverse animal species; (iii) Determine how odor cues for navigation are encoded and used in the nervous system by recording neuronal data and simulating putative neural circuits that implement these processes; (iv) Manipulate olfactory environments and neural circuitry, to evaluate model robustness. In contrast to previous attempts to understand olfactory navigation, the present strategy emphasizes mechanisms that are biologically feasible and explores the wide range of temporal and spatial scales in which animals successfully navigate. The project will generate datasets of immediate use and importance to scientists in theoretical biology and mathematics, engineering (fluid mechanics, electronic olfaction, and robotics) and biology (neuroscience, ecology and evolution).
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0.903 |
2016 — 2020 |
Verhagen, Justus V |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Multimodal Flavor Integration and Retronasal Olfaction in the Mouse @ John B. Pierce Laboratory, Inc.
ABSTRACT (Parent Grant) How taste and odor stimuli become integrated and how retronasal odorants are processed are two fundamental questions in flavor neuroscience. Functional imaging studies in humans have provided important insights into the neural bases of multimodal flavor integration, yet cannot address issues requiring higher spatio-temporal resolution or experimental manipulation of neural activity or of experience, nor evaluate the human olfactory bulb (OB). To address these limitations, the goal of the present project is to establish the transgenic mouse as a novel flavor model and to investigate the neural mechanisms of flavor integration and retronasal smell. We have now established that retronasal olfaction occurs in mice and rats as it does in humans. A first study will employ optical calcium imaging to measure spatio-temporal patterns evoked in the olfactory bulb associated with the oral ingestion of odorants by awake head-fixed transgenic GCaMP mice performing an odor detection task. We will also explore the neuro-behavioral repertoire of free-moving mice carrying a mobile head-mounted miniature imaging microscope. The effects of odor properties, active sampling (sniffing), ingestion (swallowing), hunger and flavor-experience dependent odor-taste integration on retronasal OB responses will be assessed during food exploration, approach and ingestion. We have now established that the temporal dynamics of the OB, i.e. the relative onset delays among glomeruli, are detectable by mice down to 15 ms. To determine whether retronasal temporal information in the OB, which differs fundamentally between ortho- and retronasal smell, contributes to downstream processes, we will ask what the temporal discrimination thresholds are for optogenetically modified mice during various phases of the sniff-cycle. We will next ask whether the dynamics of retronasal OB activity played back onto the OB is discriminable. Last, we will ask if different glomerular onset sequences are discriminable. Importantly, we will assess how these three measures depend on sniff-phase. Together these studies are intended to provide fundamentally new knowledge about the neural mechanisms of flavor perception using the experimentally powerful transgenic mouse models.
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0.988 |