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.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IFCN-B (50))
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Sullivan, Susan L
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Cornell University
Schools of Arts and Sciences
United States
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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
Li, Guoshi; Linster, Christiane; Cleland, Thomas A (2015) Functional differentiation of cholinergic and noradrenergic modulation in a biophysical model of olfactory bulb granule cells. J Neurophysiol 114:3177-200
Linster, Christiane; Fontanini, Alfredo (2014) Functional neuromodulation of chemosensation in vertebrates. Curr Opin Neurobiol 29:82-7
Anderson, Ross W; Strowbridge, Ben W (2014) Regulation of persistent activity in hippocampal mossy cells by inhibitory synaptic potentials. Learn Mem 21:263-71
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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