Humans and other mammals use the temporal fine structure in sounds to identify and help localize auditory objects in three-dimensional space. The broad goal of this research is both to understand how sound localization cues are processed in the brain as well as to understand how neurons in the underlying circuitry acquire the appropriate biophysical properties during development. This proposal focuses on the medial superior olive (MSO), the first and critical stage for processing interaural time differences (ITDs) from the two ears, cues that are used for horizontal sound localization as well as for understanding speech patterns in noisy environments. ITDs are computed in the MSO via the process of coincidence detection, in which the simultaneous arrival of excitatory inputs from the two ears is detected and conveyed through action potential firing with a time resolution of a few tens of microseconds. The neurons of the MSO have historically been assumed to be functionally and morphologically homogeneous. However, our preliminary data refutes this simplistic view of the MSO: we hypothesize instead that variation in dendritic morphology and electrical properties critically shapes the location of spatial receptive fields, and that these differences are in part influenced after hearing onset by the level and pattern of neural activity. We will address these questions by combining paired dendritic and somatic patch recordings, compartmental modeling, patterned LED illumination of light-sensitive channel blockers, and hearing manipulations.
Aim 1 will address the functional significance of the newly discovered tonotopic diversity in electophysiological properties of MSO neurons both in vitro using patch- clamp recordings.
Aim 2 will extend these analyses to understand how the functional diversity in MSO neurons is conferred by differences in the expression levels and properties of voltage-gated channels in the axon initial segment.
Aim 3 will explore how the diversity of dendritic structure itself shapes the temporal requirements for optimal detection of binaural coincidence. The information from these experiments will increase our understanding of the mechanisms underlying spatial hearing in mammals, as well as the developmental processes that control the formation of a critical circuit component in the MSO. As binaural hearing is important for speech perception and language acquisition in children, a mechanistic understanding of binaural circuit function and development may ultimately inform clinical strategies for addressing hearing impairments.
Humans and other mammals depend on sound localization for discrimination of speech patterns in noisy environments. As critical cues for sound localization are computed in the medial superior olive, a foundational understanding of the properties of its neurons is important for understanding normal hearing as well as the ways in which the brain is affected by hearing loss, deafness, and the introduction of auditory prosthetics.
|Zorio, Diego A R; Monsma, Scott; Sanes, Dan H et al. (2018) De novo sequencing and initial annotation of the Mongolian gerbil (Meriones unguiculatus) genome. Genomics :|
|Winters, Bradley D; Golding, Nace L (2018) Glycinergic Inhibitory Plasticity in Binaural Neurons Is Cumulative and Gated by Developmental Changes in Action Potential Backpropagation. Neuron 98:166-178.e2|
|Winters, Bradley D; Jin, Shan-Xue; Ledford, Kenneth R et al. (2017) Amplitude Normalization of Dendritic EPSPs at the Soma of Binaural Coincidence Detector Neurons of the Medial Superior Olive. J Neurosci 37:3138-3149|
|Ko, Kwang Woo; Rasband, Matthew N; Meseguer, Victor et al. (2016) Serotonin modulates spike probability in the axon initial segment through HCN channels. Nat Neurosci 19:826-34|
|Franken, Tom P; Roberts, Michael T; Wei, Liting et al. (2015) In vivo coincidence detection in mammalian sound localization generates phase delays. Nat Neurosci 18:444-52|
|Roberts, Michael T; Seeman, Stephanie C; Golding, Nace L (2014) The relative contributions of MNTB and LNTB neurons to inhibition in the medial superior olive assessed through single and paired recordings. Front Neural Circuits 8:49|
|van der Heijden, Marcel; Lorteije, Jeannette A M; Plauška, Andrius et al. (2013) Directional hearing by linear summation of binaural inputs at the medial superior olive. Neuron 78:936-48|
|Roberts, Michael T; Seeman, Stephanie C; Golding, Nace L (2013) A mechanistic understanding of the role of feedforward inhibition in the mammalian sound localization circuitry. Neuron 78:923-35|
|Khurana, Sukant; Liu, Zhiqiang; Lewis, Alan S et al. (2012) An essential role for modulation of hyperpolarization-activated current in the development of binaural temporal precision. J Neurosci 32:2814-23|
|Golding, Nace L; Oertel, Donata (2012) Synaptic integration in dendrites: exceptional need for speed. J Physiol 590:5563-9|
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