The goal of this research is to understand how the nervous system encodes information about odors. The sense of smell presents unique problems to the nervous system in terms of stimulus detection, neural encoding and recognition of complex stimuli;understanding how the brain solves these problems will likely lead to new general insights into how the brain processes information. The initial code for odors consists of patterns of activity across olfactory receptor neurons, which project to glomeruli in the olfactory bulb, the first stage of synaptic processing of olfactory information. Here, patterns of activity across thousands of receptor neurons are transformed into spatially organized maps of glomerular activation - these glomerular patterns are unique for a given odor and odor concentration. The research in this continuing project uses optical imaging methods to visualize these patterns and to investigate how they represent olfactory stimuli. Previous work built on the observation that spatial maps of receptor input to glomeruli are temporally dynamic, and asked how these dynamics participate in odor coding and shape the initial stages of olfactory processing. A key finding was that much of the temporal dynamics of odor maps are organized around the respiratory cycle, which is heavily modulated in the awake, behaving animal and is integral to the act of smelling. The experiments proposed here will investigate, for the first time, how odor sampling behavior (i.e. - `sniffing') shapes early olfactory coding at the level of the olfactory bulb and the transformation of receptor inputs into patterns of postsynaptic activity. The experiments will image receptor input to olfactory bulb glomeruli while an animal is awake and actively performing odor-guided tasks, and relate these patterns to the animal's sniffing behavior. Different patterns of sniffing will also be played back in the anesthetized animal in order to separately evaluate effects of sampling behavior and effects of behavioral state-dependent modulation of receptor inputs. The experiments will also ask how sniffing shapes the transformation of odor representations by the olfactory bulb, using electrophysiological recordings from individual olfactory bulb projection neurons during activation by odorants sampled with different sniffing patterns. In addition to testing, for the first time, several longstanding hypotheses about the role of sampling behavior in shaping odor codes, this work will be important in understanding how olfactory information is encoded and processed in the awake, behaving animal. This work has the potential to lead to new treatments for olfactory deficits or therapeutic approaches to improving odor or flavor perception in individuals with impaired nasal function.

Public Health Relevance

The sense of smell presents unique problems to the nervous system in terms of stimulus detection, neural encoding and recognition of complex stimuli;understanding how the brain solves these problems will likely lead to new general insights into how the brain processes information. This project in particular focuses on the importance of respiratory behavior in determining how the brain represents and processes olfactory information. Understanding this relationship could lead to new treatments for olfactory deficits or therapeutic approaches to improving odor or flavor perception in individuals with impaired nasal function.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC006441-11
Application #
8417714
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
2004-01-22
Project End
2014-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
11
Fiscal Year
2013
Total Cost
$288,417
Indirect Cost
$94,956
Name
University of Utah
Department
Internal Medicine/Medicine
Type
Organized Research Units
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Rothermel, Markus; Wachowiak, Matt (2014) Functional imaging of cortical feedback projections to the olfactory bulb. Front Neural Circuits 8:73
Cenier, Tristan; McGann, John P; Tsuno, Yusuke et al. (2013) Testing the sorption hypothesis in olfaction: a limited role for sniff strength in shaping primary odor representations during behavior. J Neurosci 33:79-92
Rothermel, Markus; Brunert, Daniela; Zabawa, Christine et al. (2013) Transgene expression in target-defined neuron populations mediated by retrograde infection with adeno-associated viral vectors. J Neurosci 33:15195-206
Wachowiak, Matt; Economo, Michael N; Diaz-Quesada, Marta et al. (2013) Optical dissection of odor information processing in vivo using GCaMPs expressed in specified cell types of the olfactory bulb. J Neurosci 33:5285-300
Carey, Ryan M; Wachowiak, Matt (2011) Effect of sniffing on the temporal structure of mitral/tufted cell output from the olfactory bulb. J Neurosci 31:10615-26
Wachowiak, Matt (2011) All in a sniff: olfaction as a model for active sensing. Neuron 71:962-73
Cheung, Man Ching; Carey, Ryan M; Wachowiak, Matt (2009) A method for generating natural and user-defined sniffing patterns in anesthetized or reduced preparations. Chem Senses 34:63-76
Wesson, Daniel W; Donahou, Tanya N; Johnson, Marc O et al. (2008) Sniffing behavior of mice during performance in odor-guided tasks. Chem Senses 33:581-96
Pirez, Nicolas; Wachowiak, Matt (2008) In vivo modulation of sensory input to the olfactory bulb by tonic and activity-dependent presynaptic inhibition of receptor neurons. J Neurosci 28:6360-71
Verhagen, Justus V; Engelen, Lina (2006) The neurocognitive bases of human multimodal food perception: sensory integration. Neurosci Biobehav Rev 30:613-50

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