Glycinergic axonal inhibition subserves acute spatial sensitivity to sudden increases in sound intensity

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Abstract

Locomotion generates adventitious sounds which enable detection and localization of predators and prey. Such sounds contain brisk changes or transients in amplitude. We investigated the hypothesis that ill-understood temporal specializations in binaural circuits subserve lateralization of such sound transients, based on different time of arrival at the ears (interaural time differences, ITDs). We find that Lateral Superior Olive (LSO) neurons show exquisite ITD-sensitivity, reflecting extreme precision and reliability of excitatory and inhibitory postsynaptic potentials, in contrast to Medial Superior Olive neurons, traditionally viewed as the ultimate ITD-detectors. In vivo, inhibition blocks LSO excitation over an extremely short window, which, in vitro, required synaptically-evoked inhibition. Light and electron microscopy revealed inhibitory synapses on the axon initial segment as the structural basis of this observation. These results reveal a neural vetoing mechanism with extreme temporal and spatial precision and establish the LSO as the primary nucleus for binaural processing of sound transients.

Data availability

Source data files have been provided for all figures with electrophysiological recordings and for the computational model (Figures 1,2,3,4,7,8 and supplements). Custom MATLAB code for the computational model is provided as a source code file.

Article and author information

Author details

Tom P Franken

Department of Neuroscience, KU Leuven, Leuven, Belgium

For correspondence
tfranken@salk.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7160-5152
Brian J Bondy

Department of Neuroscience and Center for Learning and Memory, UT Austin, Austin, United States

Competing interests
The authors declare that no competing interests exist.
David B Haimes

Department of Neuroscience and Center for Learning and Memory, UT Austin, Austin, United States

Competing interests
The authors declare that no competing interests exist.
Joshua Goldwyn

Department of Mathematics and Statistics, Swarthmore College, Swarthmore, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5733-9089
Nace L Golding

Department of Neuroscience and Center for Learning and Memory, UT Austin, Austin, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-4072-310X
Philip H Smith

Department of Neuroscience, University of Wisconsin-Madison, Madison, United States

Competing interests
The authors declare that no competing interests exist.
Philip Joris

University of Leuven, Leuven, Belgium

For correspondence
philip.joris@kuleuven.be

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-9759-5375

Funding

Fonds Wetenschappelijk Onderzoek (Ph.D. fellowship)

Tom P Franken

Bijzonder Onderzoeksfonds KU Leuven (OT-14-118)

Philip Joris

Fonds Wetenschappelijk Onderzoek (G.0961.11)

Philip Joris

Fonds Wetenschappelijk Onderzoek (G.0A11.13)

Philip Joris

Fonds Wetenschappelijk Onderzoek (G.091214N)

Philip Joris

National Institute on Deafness and Other Communication Disorders (DC006212)

Philip H Smith
Philip Joris

National Institute on Deafness and Other Communication Disorders (DC011403)

Nace L Golding
Philip Joris

National Institute on Deafness and Other Communication Disorders (DC006788)

Nace L Golding

National Institute on Deafness and Other Communication Disorders (1F31DC017377-01)

David B Haimes

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All in vivo procedures were approved by the KU Leuven Ethics Committee for Animal Experiments (protocol numbers P155/2008, P123/2010, P167/2012, P123/2013, P005/2014). All in vitro recording and immunohistochemistry experiments were approved by the University of Texas at Austin Animal Care and Use Committee in compliance with the recommendations of the United States National Institutes of Health.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.