The central auditory system exhibits a remarkable ability to extract information from the limited representation of the acoustic environment provided by the auditory nerve. The first central processing of this information occurs in the cochlear nucleus, where sensory information is transformed and reorganized into a set of parallel ascending pathways that each emphasizes different features of the acoustic environment. While many mechanisms are involved in these transformations in the ventral cochlear nucleus (VCN), one of the most critical elements is the differential ion channel expression among the various classes of neurons. In the first aim, the hypothesis to be tested is that the potassium channel genes Kv1.1 and Kv1.2 are critical components of the channels that form the low-threshold potassium current in bushy cells. The morphological-physiological correlation will be established between K+ channel expression and cell types at two levels: the membrane conductances in the somatic membrane and the patterns of mRNA expression for selected subsets of K+ channels. In the second aim the hypothesis to be examined is that sodium channels in VCN neurons are specialized to enhance the precise timing of action potentials and to produce high discharge rates. These experiments will lead directly to biophysically detailed neural models of sensory processing by VN neurons, and will be used to provide predictions regarding the capabilities of the first stage of central processing in both normal and damaged auditory systems.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IFCN-6 (01))
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Luethke, Lynn E
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University of North Carolina Chapel Hill
Schools of Medicine
Chapel Hill
United States
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Manis, Paul B; Campagnola, Luke (2018) A biophysical modelling platform of the cochlear nucleus and other auditory circuits: From channels to networks. Hear Res 360:76-91
Xie, Ruili; Manis, Paul B (2017) Synaptic transmission at the endbulb of Held deteriorates during age-related hearing loss. J Physiol 595:919-934
Xie, Ruili; Manis, Paul B (2017) Radiate and Planar Multipolar Neurons of the Mouse Anteroventral Cochlear Nucleus: Intrinsic Excitability and Characterization of their Auditory Nerve Input. Front Neural Circuits 11:77
Campagnola, Luke; Kratz, Megan B; Manis, Paul B (2014) ACQ4: an open-source software platform for data acquisition and analysis in neurophysiology research. Front Neuroinform 8:3
Campagnola, Luke; Manis, Paul B (2014) A map of functional synaptic connectivity in the mouse anteroventral cochlear nucleus. J Neurosci 34:2214-30
Xie, Ruili; Manis, Paul B (2014) GABAergic and glycinergic inhibitory synaptic transmission in the ventral cochlear nucleus studied in VGAT channelrhodopsin-2 mice. Front Neural Circuits 8:84
Liu, Qing; Manis, Paul B; Davis, Robin L (2014) I h and HCN channels in murine spiral ganglion neurons: tonotopic variation, local heterogeneity, and kinetic model. J Assoc Res Otolaryngol 15:585-99
Xie, Ruili; Manis, Paul B (2013) Target-specific IPSC kinetics promote temporal processing in auditory parallel pathways. J Neurosci 33:1598-614
Xie, Ruili; Manis, Paul B (2013) Glycinergic synaptic transmission in the cochlear nucleus of mice with normal hearing and age-related hearing loss. J Neurophysiol 110:1848-59
Wang, Yong; O'Donohue, Heather; Manis, Paul (2011) Short-term plasticity and auditory processing in the ventral cochlear nucleus of normal and hearing-impaired animals. Hear Res 279:131-9

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