Our long-term goal is to understand how neural circuits support auditory processing. Here, we will explore dynamic aspects of synaptic communication, their neuromodulation and plasticity, in the molecular layer and granule cell regions of the dorsal cochlear nucleus (DCN). The results of this study will reveal novel aspects of DCN circuit elements, information which will add new dimensions to the current picture of auditory and multisensory processing. The DCN functions in sound source localization and the integration of a variety of non-auditory signals, potentially for head/ear orientation or cancelatin of self-generated sound. It is also believed that the DCN plays a role in the maintenance of tinnitus, a widespread and disturbingly chronic clinical condition. The DCN is unique in the lower auditory pathway for showing robust synaptic plasticity - this is plasticity not of the auditory nerve input but rather of multisensory input, highlighting the important role that latter must have in DCN function. This proposal examines two sequential stages of multisensory processing: first in auditory granule cells and then in the DCN molecular layer. All multisensory information enters the DCN through mossy fibers which terminate in seven sub regions of granule cells. Yet, the different roles of these granule regions and what distinct forms of processing occur in each are unknown. We will therefore clarify how granule cells transform signals in order to understand the significance of computations later in the circuit. In the molecular layer, parallel fibers of granule cells terminate onto fusiform principal cells and two interneurons, the cartwheel cell and the superficial stellate cell (SSC). Here we will explore an unexpected function for the SSCs, that they mediate feedback signaling from the principal cells that facilitates activity withi the molecular layer. Lastly, we will determine how processing in granule areas and the molecular layer is controlled by the potent neuromodulators. We will use electrophysiological and optical approaches, and generate new mouse lines in which fluorophores or channelrhodopsin (ChR2) are expressed in specific DCN cell types.

Public Health Relevance

These studies will provide significant new information about how inhibitory and excitatory neurons interact dynamically in a circuit that processes auditory signals. Moreover, the results may offer new insight into the causes of the neuronal hyperactivity associated with tinnitus, and in the design of more effective auditory prosthetic devices.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
2R01DC004450-15
Application #
8451710
Study Section
Auditory System Study Section (AUD)
Program Officer
Cyr, Janet
Project Start
1999-09-01
Project End
2018-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
15
Fiscal Year
2013
Total Cost
$403,624
Indirect Cost
$136,156
Name
Oregon Health and Science University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
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

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