Synaptic mechanisms of inhibition represent some of the greatest gaps in our understanding of the processing of acoustic signals in the brainstem. The subtypes of neurons, with whom they interconnect, the efficacy of those connections, and how the size and shape of the inhibitory signals are controlled, all these remain unclear. Given the relation between inhibition as a target for drugs and disease in other brain regions it seems likely that a deep knowledge of inhibitory systems will be of clinical relevance for treating auditory disorders. In this proposal, we will address decisively each one of these points, focusing on the ubiquitous inhibitory neurotransmitter glycine. First, we will take advantage of the availability of lines of mice in which green fluorescent protein (GFP) is expressed in subsets of inhibitory cells to reveal the function and connectivity of common subtypes of auditory neurons that have been rarely studied using direct electrophysiological means. Second, we will identify mechanisms that control the duration of the inhibitory state, and focus on the role of transmitter clearance from the synaptic cleft and the promising role of GABA/glycine cotransmission in regulation of glycinergic decays. Finally, we will determine what mechanisms set whether glycine excites or inhibits postsynaptic neurons.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC004450-13
Application #
8125045
Study Section
Auditory System Study Section (AUD)
Program Officer
Cyr, Janet
Project Start
1999-09-01
Project End
2013-08-31
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
13
Fiscal Year
2011
Total Cost
$367,919
Indirect Cost
Name
Oregon Health and Science University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Lu, Hsin-Wei; Balmer, Timothy S; Romero, Gabriel E et al. (2017) Slow AMPAR Synaptic Transmission Is Determined by Stargazin and Glutamate Transporters. Neuron 96:73-80.e4
Irie, Tomohiko; Trussell, Laurence O (2017) Double-Nanodomain Coupling of Calcium Channels, Ryanodine Receptors, and BK Channels Controls the Generation of Burst Firing. Neuron 96:856-870.e4
Tang, Zheng-Quan; Trussell, Laurence O (2017) Serotonergic Modulation of Sensory Representation in a Central Multisensory Circuit Is Pathway Specific. Cell Rep 20:1844-1854
Lu, Hsin-Wei; Trussell, Laurence O (2016) Spontaneous Activity Defines Effective Convergence Ratios in an Inhibitory Circuit. J Neurosci 36:3268-80
Yaeger, Daniel B; Trussell, Laurence O (2016) Auditory Golgi cells are interconnected predominantly by electrical synapses. J Neurophysiol 116:540-51
Balmer, Timothy S; Trussell, Laurence O (2016) Quantum Disentanglement: Electrical Analysis of the Complex Roles of Ions in Filling Vesicles with Glutamate. Neuron 90:667-9
Borges-Merjane, Carolina; Trussell, Laurence O (2015) ON and OFF unipolar brush cells transform multisensory inputs to the auditory system. Neuron 85:1029-42
Yaeger, Daniel B; Trussell, Laurence O (2015) Single granule cells excite Golgi cells and evoke feedback inhibition in the cochlear nucleus. J Neurosci 35:4741-50
Tang, Zheng-Quan; Trussell, Laurence O (2015) Serotonergic regulation of excitability of principal cells of the dorsal cochlear nucleus. J Neurosci 35:4540-51
Apostolides, Pierre F; Trussell, Laurence O (2014) Chemical synaptic transmission onto superficial stellate cells of the mouse dorsal cochlear nucleus. J Neurophysiol 111:1812-22

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