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.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
Project #
Application #
Study Section
Auditory System Study Section (AUD)
Program Officer
Cyr, Janet
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Oregon Health and Science University
Schools of Medicine
United States
Zip Code
Apostolides, Pierre F; Trussell, Laurence O (2014) Control of interneuron firing by subthreshold synaptic potentials in principal cells of the dorsal cochlear nucleus. Neuron 83:324-30
Huang, Hai; Trussell, Laurence O (2014) Presynaptic HCN channels regulate vesicular glutamate transport. Neuron 84:340-6
Apostolides, Pierre F; Trussell, Laurence O (2014) Superficial stellate cells of the dorsal cochlear nucleus. Front Neural Circuits 8:63
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
Apostolides, Pierre F; Trussell, Laurence O (2013) Rapid, activity-independent turnover of vesicular transmitter content at a mixed glycine/GABA synapse. J Neurosci 33:4768-81
Kuo, Sidney P; Trussell, Laurence O (2011) Spontaneous spiking and synaptic depression underlie noradrenergic control of feed-forward inhibition. Neuron 71:306-18
Huang, Hai; Trussell, Laurence O (2011) KCNQ5 channels control resting properties and release probability of a synapse. Nat Neurosci 14:840-7
Roberts, Michael T; Trussell, Laurence O (2010) Molecular layer inhibitory interneurons provide feedforward and lateral inhibition in the dorsal cochlear nucleus. J Neurophysiol 104:2462-73
Bender, Kevin J; Trussell, Laurence O (2009) Axon initial segment Ca2+ channels influence action potential generation and timing. Neuron 61:259-71
Balakrishnan, Veeramuthu; Kuo, Sidney P; Roberts, Patrick D et al. (2009) Slow glycinergic transmission mediated by transmitter pooling. Nat Neurosci 12:286-94

Showing the most recent 10 out of 19 publications