Sensory inputs to the olfactory system are initially processed by neural circuits in olfactory bulb (OB) glomeruli. This circuitry is targeted by centrifugal inputs from neuromodulatory centers. OB output via mitral/tufted (MT) cells shows remarkable modulation of sensory responses in the awake animal. Knowing how these earliest stages of odor information processing are modulated is critical to fully understanding olfactory system function. This project will investigate - for the first time - how acetylcholine (ACh) and serotonin (5HT) modulate sensory processing in glomerular circuits. The research builds on recent advances in our understanding of these circuits and their importance in shaping OB output. The project will integrate information from OB slices and anesthetized and awake head-fixed mice. This multidimensional approach aims to link the modulation of glomerular circuits to the activation of specific neuromodulatory systems - cholinergic inputs from the diagonal band and serotonergic inputs from the raphe nuclei. Our working hypothesis is that ACh and 5HT differentially modulate glomerular processing to shape both pre- and postsynaptic inhibition as well as MT cell excitability. We further hypothesize that ACh modulation reduces the impact of sensory input while at the same time increasing the excitability of MT cells. This could limit odor detection but increase discrimination ability. The proposed research is a highly integrated effort from two established investigators to understand the modulation of early olfactory processing at levels ranging from cells and circuits to single neurons in anesthetized and unanesthetized animals.

Public Health Relevance

Neuromodulatory systems have widespread effects on brain function, including on sensory systems, and dysfunction in neuromodulatory pathways is linked to diseases that profoundly effect human health, including depression, schizophrenia and Alzheimer's disease. This project investigates the roles that cholinergic and serotonergic modulation play in the initial detection and processing of sensory information in the earliest levels of the olfactory pathway. This should lead to a greater understanding of how neuromodulatory systems enhance information processing and sensory perception, and potentially lead to improved treatments for diseases linked to these systems.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Somatosensory and Chemosensory Systems Study Section (SCS)
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Sullivan, Susan L
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University of Maryland Baltimore
Anatomy/Cell Biology
Schools of Medicine
United States
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Zhou, Fu-Wen; Puche, Adam C; Shipley, Michael T (2018) Short-Term Plasticity at Olfactory Cortex to Granule Cell Synapses Requires CaV2.1 Activation. Front Cell Neurosci 12:387
Liu, Shaolin; Puche, Adam C; Shipley, Michael T (2016) The Interglomerular Circuit Potently Inhibits Olfactory Bulb Output Neurons by Both Direct and Indirect Pathways. J Neurosci 36:9604-17
Cockerham, Renee; Liu, Shaolin; Cachope, Roger et al. (2016) Subsecond Regulation of Synaptically Released Dopamine by COMT in the Olfactory Bulb. J Neurosci 36:7779-85
Brill, Julia; Shao, Zuoyi; Puche, Adam C et al. (2016) Serotonin increases synaptic activity in olfactory bulb glomeruli. J Neurophysiol 115:1208-19
Brunert, Daniela; Tsuno, Yusuke; Rothermel, Markus et al. (2016) Cell-Type-Specific Modulation of Sensory Responses in Olfactory Bulb Circuits by Serotonergic Projections from the Raphe Nuclei. J Neurosci 36:6820-35
Carey, Ryan M; Sherwood, William Erik; Shipley, Michael T et al. (2015) Role of intraglomerular circuits in shaping temporally structured responses to naturalistic inhalation-driven sensory input to the olfactory bulb. J Neurophysiol 113:3112-29
Liu, Shaolin; Shao, Zuoyi; Puche, Adam et al. (2015) Muscarinic receptors modulate dendrodendritic inhibitory synapses to sculpt glomerular output. J Neurosci 35:5680-92
Rothermel, Markus; Wachowiak, Matt (2014) Functional imaging of cortical feedback projections to the olfactory bulb. Front Neural Circuits 8:73
Rothermel, Markus; Carey, Ryan M; Puche, Adam et al. (2014) Cholinergic inputs from Basal forebrain add an excitatory bias to odor coding in the olfactory bulb. J Neurosci 34:4654-64
Shao, Zuoyi; Puche, Adam C; Shipley, Michael T (2013) Intraglomerular inhibition maintains mitral cell response contrast across input frequencies. J Neurophysiol 110:2185-91

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