Glomerular circuits are important. They transform sensory input into output signals that impact all downstream olfactory networks. Inhibition is key to these transforms. Intraglomerular inhibition presynaptically regulates sensory synapses and provides feedback and feed forward inhibition that shapes the strength and temporal structure of M/TC responses to sensory signals. Less is known about interglomerular inhibition. Exciting new data show that short axon cells, which form the interglomerular circuit, co-release GABA and DA. These co-transmitters trigger a temporally biphasic inhibitory-excitatory response in external tufted cells, neurons critical to glomerular circuit function. They also generate strong, temporally asymmetric, direct inhibition of M/TCs such that early-activated glomeruli inhibit their later activated neighbors, leading to "The early bird gets the worm" hypothesis. These discoveries were made using optogenetics combined with recordings from identified gene-targeted cell-type specific neurons. Little is known about DA release or it's metabolism in the bulb. Fast Scan Cyclic Voltammetry will be used to define the kinetics of DA release in vitro and in vivo. New data suggest that FDA-approved COMT inhibitors may enhance bulb DA function;this could benefit Parkinson's patients. We will test this hypothesis. Inhibitory-inhibitory interactions among inter- and intraglomerular neurons have not been explored. Pilot data using optogenetics combined with identified cell recordings indicate robust interactions. We will define inhibitory-inhibitory interactions, their synaptic dynamics and how they shape intra- and interglomerular signaling.

Public Health Relevance

Glomeruli circuits are important. They transform unprocessed sensory signals into M/TC outputs that impact all downstream olfactory networks. Inhibition plays a key role in these transforms. Intraglomerular regulates the strength and temporal structure of glomerular output responses to sensory input but less is known about interglomerular inhibition. Exciting new data indicate that the interglomerular synapses co- release GABA and DA, which trigger a temporally bi-phasic inhibition-excitation response in in neighboring glomeruli to gate sensory coding during sniffing. DA and olfaction are impaired in Parkinson's disease. We will determine if FDA-approved COMT inhibitors ameliorate olfactory deficits in Parkinson's. New data using optogenetics indicate that interactions among glomerular inhibitory neurons are robust. We will investigate how these inhibitory-inhibitory interactions shape odor perception.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01DC005676-16
Application #
8685934
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
City
Baltimore
State
MD
Country
United States
Zip Code
21201
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
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
Brill, Julia; Shao, Zuoyi; Puche, Adam C et al. (2016) Serotonin increases synaptic activity in olfactory bulb glomeruli. J Neurophysiol 115:1208-19
Liu, Shaolin; Shao, Zuoyi; Puche, Adam et al. (2015) Muscarinic receptors modulate dendrodendritic inhibitory synapses to sculpt glomerular output. J Neurosci 35:5680-92
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
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
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; Liu, Shaolin et al. (2012) Intraglomerular inhibition shapes the strength and temporal structure of glomerular output. J Neurophysiol 108:782-93
Liu, Shaolin; Aungst, Jason L; Puche, Adam C et al. (2012) Serotonin modulates the population activity profile of olfactory bulb external tufted cells. J Neurophysiol 107:473-83

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