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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC010915-03
Application #
8413776
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
2011-02-01
Project End
2016-01-31
Budget Start
2013-02-01
Budget End
2014-01-31
Support Year
3
Fiscal Year
2013
Total Cost
$411,509
Indirect Cost
$96,499
Name
University of Maryland Baltimore
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
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
Liu, Shaolin; Plachez, Celine; Shao, Zuoyi et al. (2013) Olfactory bulb short axon cell release of GABA and dopamine produces a temporally biphasic inhibition-excitation response in external tufted cells. J Neurosci 33:2916-26
Shao, Zuoyi; Puche, Adam C; Shipley, Michael T (2013) Intraglomerular inhibition maintains mitral cell response contrast across input frequencies. J Neurophysiol 110:2185-91
Parrish-Aungst, S; Kiyokage, E; Szabo, G et al. (2011) Sensory experience selectively regulates transmitter synthesis enzymes in interglomerular circuits. Brain Res 1382:70-6