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.
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.
|Dibattista, Michele; Pifferi, Simone; Boccaccio, Anna et al. (2017) The long tale of the calcium activated Cl- channels in olfactory transduction. Channels (Austin) 11:399-414|
|Pietra, Gianluca; Dibattista, Michele; Menini, Anna et al. (2016) The Ca2+-activated Cl- channel TMEM16B regulates action potential firing and axonal targeting in olfactory sensory neurons. J Gen Physiol 148:293-311|
|Dibattista, Michele; Reisert, Johannes (2016) The Odorant Receptor-Dependent Role of Olfactory Marker Protein in Olfactory Receptor Neurons. J Neurosci 36:2995-3006|
|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|
|Mainland, Joel D; Lundström, Johan N; Reisert, Johannes et al. (2014) From molecule to mind: an integrative perspective on odor intensity. Trends Neurosci 37:443-54|
|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|
|Su, Chih-Ying; Menuz, Karen; Reisert, Johannes et al. (2012) Non-synaptic inhibition between grouped neurons in an olfactory circuit. Nature 492:66-71|
|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|
Showing the most recent 10 out of 13 publications