We propose an interdisciplinary study of the behavioral consequences and the cellular and synaptic basis for the modulation of olfactory bulb function by centrifugal noradrenergic innervation. The proposal is based on behavioral experiments where we show that microinfusion of both 1 and 2 adrenergic antagonists confined to the olfactory bulb interferes with the ability of mice to discriminate between structurally related odors. In addition, we present patch clamp experiments in olfactory bulb slices that show both acute and long term effects of noradrenaline on mitral cell function that likely underlie the effect of the adrenergic antagonists in vivo. We hypothesize that noradrenaline modulates odor responsiveness and mitral cell action potential firing and that these changes in mitral cell function contribute to the behavioral discrimination of closely related odors. In order to test this hypothesis, we will utilize the powerful techniques of assessment of olfactory ability through computer-assisted operant conditioning and adrenergic receptor pharmacology with patch clamp studies of modulation of mitral cell function in olfactory bulb slices.
Two aims are proposed.
Aim 1. Test the hypothesis that centrifugal noradrenergic modulation of olfactory bulb function is necessary for discrimination of closely related odors.
Aim 2. Test the hypothesis that noradrenaline modulates cellular properties and mitral cell spike activity in mouse olfactory bulb slices. This interdisciplinary approach will allow us to critically assess the cellular and synaptic basis of modulation of olfactory behavior by noradrenergic modification of olfactory bulb function.7. Project Narrative. In humans, disorders of the sense of smell are encountered in diseases such as Alzheimer's (Doty, 1991;Rawson, 2000), bipolar depression (Hahn et al., 2005) and schizophrenia (Turetsky et al., 2003). This grant will study noradrenergic modulation of olfactory bulb function. The study of noradrenergic modulation is relevant to schizophrenia (Yamamoto and Hornykiewicz, 2004) whose etiology we study in the Restrepo laboratory.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC000566-22
Application #
7902153
Study Section
Special Emphasis Panel (ZRG1-IFCN-K (03))
Program Officer
Davis, Barry
Project Start
1988-12-12
Project End
2012-08-31
Budget Start
2010-09-01
Budget End
2011-08-31
Support Year
22
Fiscal Year
2010
Total Cost
$349,010
Indirect Cost
Name
University of Colorado Denver
Department
Biology
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Pouille, Frederic; Schoppa, Nathan E (2018) Cannabinoid Receptors Modulate Excitation of an Olfactory Bulb Local Circuit by Cortical Feedback. Front Cell Neurosci 12:47
Ozbay, Baris N; Futia, Gregory L; Ma, Ming et al. (2018) Three dimensional two-photon brain imaging in freely moving mice using a miniature fiber coupled microscope with active axial-scanning. Sci Rep 8:8108
Li, Anan; Guthman, Ethan M; Doucette, Wilder T et al. (2017) Behavioral Status Influences the Dependence of Odorant-Induced Change in Firing on Prestimulus Firing Rate. J Neurosci 37:1835-1852
Pouille, Frederic; McTavish, Thomas S; Hunter, Lawrence E et al. (2017) Intraglomerular gap junctions enhance interglomerular synchrony in a sparsely connected olfactory bulb network. J Physiol 595:5965-5986
Zhou, Yang; Wang, Xiaojie; Cao, Tiantian et al. (2017) Insulin Modulates Neural Activity of Pyramidal Neurons in the Anterior Piriform Cortex. Front Cell Neurosci 11:378
Castillo-Azofeifa, David; Losacco, Justin T; Salcedo, Ernesto et al. (2017) Sonic hedgehog from both nerves and epithelium is a key trophic factor for taste bud maintenance. Development 144:3054-3065
Bourne, Jennifer N; Schoppa, Nathan E (2017) Three-dimensional synaptic analyses of mitral cell and external tufted cell dendrites in rat olfactory bulb glomeruli. J Comp Neurol 525:592-609
Ozbay, Baris N; Losacco, Justin T; Cormack, Robert et al. (2015) Miniaturized fiber-coupled confocal fluorescence microscope with an electrowetting variable focus lens using no moving parts. Opt Lett 40:2553-6
Li, Anan; Gire, David H; Restrepo, Diego (2015) ? spike-field coherence in a population of olfactory bulb neurons differentiates between odors irrespective of associated outcome. J Neurosci 35:5808-22
ten Oever, Sanne; Schroeder, Charles E; Poeppel, David et al. (2014) Rhythmicity and cross-modal temporal cues facilitate detection. Neuropsychologia 63:43-50

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