Animals live in an environment of constantly changing and complex odorous signals, which are delivered by the inhaled air to olfactory receptor neurons (ORNs) in the nasal cavity. ORNs recognize odorants and convert odorant stimulation into action potentials to be conveyed to the first relay station in the brain, the olfactory bulb. This is achieved by activation of odorant receptors, leading to cAMP generation via a G protein-coupled cascade and the opening of ion channels present on the olfactory cilia and subsequent depolarization. Odorant specificity is provided by the expression of only one type of odorant receptor in a given ORN out of ~1000 different receptors in mice and 350 in humans. Most major components of olfactory signal transduction have been identified. Our goal is to determine what limits and controls the kinetics with which olfactory transduction components interact, how this controls action potential generation and coding and what the behavioral implications are for, in particular, odorant discrimination and initiation of sniffing. Using electrophysiological techniques, we will investigate how mouse ORNs transduce odorant stimulation. Using rapid, repetitive stimulation designed to simulate high-frequency, sniffing-driven odorant delivery, we will establish whether ORNs merely report these rapid changes in odorant concentration or if in fact they themselves actively process this information in a stimulation-frequency-dependent manner. We will determine the functional role in olfactory transduction kinetics of olfactory marker protein (the function of which has not been found since its discovery in 1972) as well as determining the role of different odorant receptors in shaping the time-course of the odorant-induced response. The importance of fast and precise olfactory transduction will be studied using behavioral testing on genetically altered mice to investigate speed-accuracy tradeoff in odorant identification. Monitoring the breathing frequency during active olfactory exploration will allow us to establish the contribution of ORN kinetics and peripheral-versus-central influence on controlling changes in breathing and sniffing rates.

Public Health Relevance

The proposed work will address the importance of both precise timing and fast transduction of odorous signals by G protein-coupled receptors in olfactory receptor neurons from the single-cell to the complex-behavioral levels such as tracking a food source or avoiding a predator. The work has broader implications in that the results will yield fundamental insights into how members of the G protein-coupled receptor family (which comprise a large part of the genome) and neurons that express them, control time-dependent cellular processes ranging from heart beat regulation to conveying hormonal signals.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC009613-05
Application #
8620640
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
2010-03-01
Project End
2015-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
5
Fiscal Year
2014
Total Cost
$298,508
Indirect Cost
$92,808
Name
Monell Chemical Senses Center
Department
Type
DUNS #
088812565
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Reisert, Johannes; Golden, Glen J; Matsumura, Koichi et al. (2014) Comparing thoracic and intra-nasal pressure transients to monitor active odor sampling during odor-guided decision making in the mouse. J Neurosci Methods 221:8-14
Kato, Aya; Reisert, Johannes; Ihara, Sayoko et al. (2014) Evaluation of the role of g protein-coupled receptor kinase 3 in desensitization of mouse odorant receptors in a Mammalian cell line and in olfactory sensory neurons. Chem Senses 39:771-80
Li, Feng; Ponissery-Saidu, Samsudeen; Yee, Karen K et al. (2013) Heterotrimeric G protein subunit G?13 is critical to olfaction. J Neurosci 33:7975-84
Ponissery Saidu, Samsudeen; Stephan, Aaron B; Talaga, Anna K et al. (2013) Channel properties of the splicing isoforms of the olfactory calcium-activated chloride channel Anoctamin 2. J Gen Physiol 141:691-703
Ponissery Saidu, Samsudeen; Dibattista, Michele; Matthews, Hugh R et al. (2012) Odorant-induced responses recorded from olfactory receptor neurons using the suction pipette technique. J Vis Exp :e3862
Reisert, Johannes; Zhao, Haiqing (2011) Perspectives on: information and coding in mammalian sensory physiology: response kinetics of olfactory receptor neurons and the implications in olfactory coding. J Gen Physiol 138:303-10
Ghatpande, Ambarish S; Reisert, Johannes (2011) Olfactory receptor neuron responses coding for rapid odour sampling. J Physiol 589:2261-73
Reisert, Johannes (2010) Origin of basal activity in mammalian olfactory receptor neurons. J Gen Physiol 136:529-40