The overall goal of this project is to directly test how cholinergic input from the nucleus of the horizontal limb of the diagonal band of Broca (HDB) alters olfactory bulb (OB) glomerular circuits and how this modulation ultimately affects odor coding, perception, and learning. We will use of both wide-field and 2-photon in vivo and in vitro calcium imaging in mice expressing genetically encoded indicators of neuronal activity in defined OB cell types, to test the novel overarching hypothesis that synaptically-released acetylcholine bidirectionally modulates mitral/tufted cell odor responses as a function of the prevailing odor intensity. We further test the hypothesis that this modulation is due to opposing muscarinic and nicotinic receptor actions on inhibitory periglomerular cells that differentially regulate the strength of presynaptic inhibition of olfactory sensory neuron input to the glomeruli. Using imaging and well characterized olfactory-mediated behaviors, we will also investigate how this cholinergic modulation of the glomerular odor representation affects odor perception and learning. Specifically, we test the hypotheses that HDB-evoked acetylcholine release in the OB: (1) enhances olfactory sensitivity, (2) dishabituates odor responses adapted at the peripheral olfactory sensory neuron level and (3) is critical for associative olfactory learning. By investigating receptor type-specific cholinergic modulation in morphologically- and physiologically-distinct neuron types at both the population and single cell levels, the experiments of this proposal will for the first time elucidate how cholinergic modulation of neural odor responses in the OB impacts olfactory perception and learning behaviorally. The overall findings will dramatically advance our understanding of how acetylcholine modulates sensory representation, odor coding, perception and behavior.

Public Health Relevance

Olfactory dysfunction is an early indicator of several major neurological diseases in humans including Alzheimer's and Parkinson's diseases. As the loss of cholinergic neurons is a hallmark in both of these diseases, it is particularly important to understand the basic mechanisms by which cholinergic modulation affects the neuronal circuits involved in sensory processing, learning, and memory which could help in the diagnosis and treatment of these diseases. This proposal will elucidate how acetylcholine release in a primary cortical sensory structure, the olfactory bulb, impacts sensory coding, stimulus salience, perception, and olfactory learning will provide insights into sensory and cognitive impairments with disturbances in cholinergic function.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC013779-04
Application #
9429095
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
2015-03-01
Project End
2020-02-28
Budget Start
2018-03-01
Budget End
2019-02-28
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38103
Bendahmane, Mounir; Ogg, M Cameron; Ennis, Matthew et al. (2016) Increased olfactory bulb acetylcholine bi-directionally modulates glomerular odor sensitivity. Sci Rep 6:25808
McAfee, Samuel Stuart; Ogg, Mary Cameron; Ross, Jordan M et al. (2016) Minimally invasive highly precise monitoring of respiratory rhythm in the mouse using an epithelial temperature probe. J Neurosci Methods 263:89-94
Ogg, M Cameron; Bendahamane, Mounir; Fletcher, Max L (2015) Habituation of glomerular responses in the olfactory bulb following prolonged odor stimulation reflects reduced peripheral input. Front Mol Neurosci 8:53