This proposal presents a multidisciplinary approach to understanding a fundamental property of sensory processing: the modulation of sensory perception by acetylcholine. The proposal addresses this question in the olfactory bulb of rats, using a combination of computational modeling, brain slice physiology, in vivo electrophysiology and behavioral pharmacology. The mammalian olfactory system offers several unique advantages for such studies. First, the olfactory system is anatomically relatively simple and this simplicity has resulted in an extensive knowledge of its synaptic connections and physiology. Second, because olfactory bulb principal neurons are a single synapse removed from sensory neurons, a relatively clear relationship between neural representations in the bulb and the perceptual properties of olfactory signals has been established. Third, this knowledge in turn has enabled the development of computational models crucial for the interpretation and integration of experimental data. A collaborative effort between three labs will investigate the interplay between muscarinic and nicotinic receptor activation and the functional consequences of their coordinated activation. Specifically, we will (1) determine the effects of muscarinic and nicotinic receptor activation on olfactory bulb neural circuits in a detailed biophysical model, (2) test the cellular and synaptic effects of such modulation using brain slice electrophysiology, (3) use in vivo electrophysiology to determine the effect of cholinergic modulation on odor responses, and (4) test the functional predictions arising from these experiments in behavioral pharmacology experiments. Taken together, the proposed simulations and experiments will elucidate how nicotinic and muscarinic receptors interact within a coordinated neural circuit to improve contrast and signal-to-noise properties in early olfactory processing.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC009948-05
Application #
8277380
Study Section
Special Emphasis Panel (ZRG1-IFCN-B (50))
Program Officer
Sullivan, Susan L
Project Start
2008-07-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2014-06-30
Support Year
5
Fiscal Year
2012
Total Cost
$353,731
Indirect Cost
$93,885
Name
Cornell University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Devore, Sasha; Pender-Morris, Nathaniel; Dean, Owen et al. (2016) Basal forebrain dynamics during nonassociative and associative olfactory learning. J Neurophysiol 115:423-33
de Almeida, Licurgo; Idiart, Marco; Dean, Owen et al. (2016) Internal Cholinergic Regulation of Learning and Recall in a Model of Olfactory Processing. Front Cell Neurosci 10:256
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Linster, Christiane; Fontanini, Alfredo (2014) Functional neuromodulation of chemosensation in vertebrates. Curr Opin Neurobiol 29:82-7
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Devore, Sasha; de Almeida, Licurgo; Linster, Christiane (2014) Distinct roles of bulbar muscarinic and nicotinic receptors in olfactory discrimination learning. J Neurosci 34:11244-60
Anderson, Ross W; Strowbridge, Ben W (2014) α-Band oscillations in intracellular membrane potentials of dentate gyrus neurons in awake rodents. Learn Mem 21:656-61
Devore, Sasha; Lee, Joshua; Linster, Christiane (2013) Odor preferences shape discrimination learning in rats. Behav Neurosci 127:498-504
de Almeida, Licurgo; Idiart, Marco; Linster, Christiane (2013) A model of cholinergic modulation in olfactory bulb and piriform cortex. J Neurophysiol 109:1360-77
Dillon, T Samuel; Fox, Laura C; Han, Crystal et al. (2013) 17β-estradiol enhances memory duration in the main olfactory bulb in CD-1 mice. Behav Neurosci 127:923-31

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