Glycinergic axonal inhibition subserves acute spatial sensitivity to sudden increases in sound intensity
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
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.
Reviewing Editor
- Catherine Emily Carr, University of Maryland, United States
Publication history
- Received: August 17, 2020
- Accepted: June 12, 2021
- Accepted Manuscript published: June 14, 2021 (version 1)
- Version of Record published: June 28, 2021 (version 2)
Copyright
© 2021, Franken et al.
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.
Metrics
-
- 747
- Page views
-
- 132
- Downloads
-
- 3
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Developmental Biology
- Neuroscience
How does wiring specificity of neural maps emerge during development? Formation of the adult Drosophila olfactory glomerular map begins with patterning of projection neuron (PN) dendrites at the early pupal stage. To better understand the origin of wiring specificity of this map, we created genetic tools to systematically characterize dendrite patterning across development at PN type-specific resolution. We find that PNs use lineage and birth order combinatorially to build the initial dendritic map. Specifically, birth order directs dendrite targeting in rotating and binary manners for PNs of the anterodorsal and lateral lineages, respectively. Two-photon- and adaptive optical lattice light-sheet microscope-based time-lapse imaging reveals that PN dendrites initiate active targeting with direction-dependent branch stabilization on the timescale of seconds. Moreover, PNs that are used in both the larval and adult olfactory circuits prune their larval-specific dendrites and re-extend new dendrites simultaneously to facilitate timely olfactory map organization. Our work highlights the power and necessity of type-specific neuronal access and time-lapse imaging in identifying wiring mechanisms that underlie complex patterns of functional neural maps.
-
- Neuroscience
Comparing connectomes can help explain how neural connectivity is related to genetics, disease, development, learning, and behavior. However, making statistical inferences about the significance and nature of differences between two networks is an open problem, and such analysis has not been extensively applied to nanoscale connectomes. Here, we investigate this problem via a case study on the bilateral symmetry of a larval Drosophila brain connectome. We translate notions of'bilateral symmetry' to generative models of the network structure of the left and right hemispheres, allowing us to test and refine our understanding of symmetry. We find significant differences in connection probabilities both across the entire left and right networks and between specific cell types. By rescaling connection probabilities or removing certain edges based on weight, we also present adjusted definitions of bilateral symmetry exhibited by this connectome. This work shows how statistical inferences from networks can inform the study of connectomes, facilitating future comparisons of neural structures.