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.

Principal neuron diversity in the murine lateral superior olive supports multiple sound localization strategies and segregation of information in higher processing centers

“…The most recent in vivo reports utilized whole-cell technique in gerbils and also found onset and multi-spiking LSO neurons 7 , 8 . These authors found that multi-spiking cells were near the margins of the nucleus, and they tended to have lower somatic synapse coverage suggesting they were not PNs but the marginal cells described by Helfert et al 62 .…”

“…The onset cells tended to have greater somatic synapse coverage and were proposed to be the PNs designated by Helfert which made up 79% of LSO neurons. Franken et al also found that the LSO neurons with onset firing responses had short spike amplitudes normally associated with time-coding-specialized medial superior olive (MSO) neurons 63 and excelled at encoding of transients 8 . Thus, the authors proposed that a large majority of LSO neurons are time-coding-specialized, and the dominant function of LSO lies with ITD coding.…”

Harmonic Cancellation—A Fundamental of Auditory Scene Analysis

“…, 2015 ; Chen et al , 2019 ). A recent study reported evidence for an inhibitory “veto” mechanism at the axon initial segment of LSO principal neurons, with very narrow tuning to inter-aural time differences ( Franken et al. , 2021 ).…”

“…A recent study reported evidence for an inhibitory “veto” mechanism at the axon initial segment of LSO principal neurons, with very narrow tuning to inter-aural time differences ( Franken et al. , 2021 ). Transmission failure at reputed “secure” synapses in CN and MNTB might conceivably reflect a similar veto mechanism ( Mc Laughlin et al , 2008 ; Englitz et al , 2009 ; Stasiak et al , 2018 ).…”

High-resolution volumetric imaging constrains compartmental models to explore synaptic integration and temporal processing by cochlear nucleus globular bushy cells

“…Interestingly, the AIS of each BC is contacted by multiple small inputs. Inhibitory inputs onto the AIS of other neuron types have been shown experimentally and computationally to modulate spike generation ( Bae et al, 2021 ; Schneider-Mizell et al, 2021 ; Veres et al, 2014 ; Franken et al, 2021 ). We reveal that in nearly all BCs one of the large somatic inputs extends onto the hillock and AIS.…”