Acitivity in auditory nerve fibers is conveyed snyaptically to the cochlear nuclei, where the first stages of neural integration of auditory information take place. Several types of cells can be distinguished in the cochlear nuclei that have their own characteristic pharmacology, morphology, inputs, pattern of projection, electrical characteristics and response patterns to tones. Because many of these cells are interconnected and receive efferent inputs from higher centers, the pattern of activity in the cochlear nucleus to the complex spatial and temporal patterns of activity in the auditory nerve that are evoked by natural sounds are not understood. Experiments are proposed to define the neuronal circuitry in the psoteroyentral and dorsal cochlear nuclei. In brain slices, stimulation of the auditory nerve evokes not only monosynaptic responses but also polysynaptic responses through neuronal circuitry contained in the slice. Elements of the circuit will be separated physically, pharmacologically and electrophysiologically. Synaptic responses will be recorded intracellularly to electrical stimulation of the auditory nerve and of other fiber tracts. Circuitry will be simplified by cutting away inputs. The connections that remain will be differentially activated with focal stimulation and antagonists to neurotransmitters will be used to separate synaptic responses that are activated together. The synaptic responses of a single cell will be related to the activity of other cells in the slice through a map of extracellularly recorded, evoked responses. Because the cochlear nuclei encode sound tonotopically, the position of activity in the slice will reflect, in a crude way, the frequency of sound encoded by the electrically stimulated fibers. No natural sounds activate large groups of auditory nerve fibers simultaneously as do auditory prostheses; the limitations of auditory prostheses result from the unnatural patterns of activity evoked in the auditory pathway. The patterns that will be recorded from slices in response to electrical stimulation of the auditory nerve, will be unnatural in precisely the same way as auditory prostheses. By understanding the neuronal circuitry in the cochlear nuclei that underlies these patterns, it may be possible to improve the performance of prostheses by altering critical spatial or temporal stimulation patterns.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
8R01DC000176-08
Application #
3215989
Study Section
Hearing Research Study Section (HAR)
Project Start
1981-07-01
Project End
1992-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
8
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Cao, Xiao-Jie; Oertel, Donata (2017) Genetic perturbations suggest a role of the resting potential in regulating the expression of the ion channels of the KCNA and HCN families in octopus cells of the ventral cochlear nucleus. Hear Res 345:57-68
Ison, James R; Allen, Paul D; Oertel, Donata (2017) Deleting the HCN1 Subunit of Hyperpolarization-Activated Ion Channels in Mice Impairs Acoustic Startle Reflexes, Gap Detection, and Spatial Localization. J Assoc Res Otolaryngol 18:427-440
Oertel, Donata; Cao, Xiao-Jie; Ison, James R et al. (2017) Cellular Computations Underlying Detection of Gaps in Sounds and Lateralizing Sound Sources. Trends Neurosci 40:613-624
Wright, Samantha; Hwang, Youngdeok; Oertel, Donata (2014) Synaptic transmission between end bulbs of Held and bushy cells in the cochlear nucleus of mice with a mutation in Otoferlin. J Neurophysiol 112:3173-88
McGinley, Matthew J; Liberman, M Charles; Bal, Ramazan et al. (2012) Generating synchrony from the asynchronous: compensation for cochlear traveling wave delays by the dendrites of individual brainstem neurons. J Neurosci 32:9301-11
Golding, Nace L; Oertel, Donata (2012) Synaptic integration in dendrites: exceptional need for speed. J Physiol 590:5563-9
Oertel, Donata; Wright, Samantha; Cao, Xiao-Jie et al. (2011) The multiple functions of T stellate/multipolar/chopper cells in the ventral cochlear nucleus. Hear Res 276:61-9
Oertel, Donata (2011) GluA4 sustains sensing of sounds through stable, speedy, sumptuous, spineless synapses. J Physiol 589:4089-90
Cao, Xiao-Jie; Oertel, Donata (2011) The magnitudes of hyperpolarization-activated and low-voltage-activated potassium currents co-vary in neurons of the ventral cochlear nucleus. J Neurophysiol 106:630-40
Cao, Xiao-Jie; Oertel, Donata (2010) Auditory nerve fibers excite targets through synapses that vary in convergence, strength, and short-term plasticity. J Neurophysiol 104:2308-20

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