Long-term potentiation of glycinergic synapses by semi-natural stimulation patterns during tonotopic map refinement

Eva C Bach,Karl Kandler

doi:10.1038/s41598-020-73050-y

Eva C Bach, Karl Kandler

Open Access

https://doi.org/10.1038/s41598-020-73050-y

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Abstract

Before the onset of hearing, cochlea-generated patterns of spontaneous spike activity drive the maturation of central auditory circuits. In the glycinergic sound localization pathway from the medial nucleus of the trapezoid body (MNTB) to the lateral superior olive (LSO) this spontaneous activity guides the strengthening and silencing of synapses which underlies tonotopic map refinement. However, the mechanisms by which patterned activity regulates synaptic refinement in the MNTB-LSO pathway are still poorly understood. To address this question, we recorded from LSO neurons in slices from prehearing mice while stimulating MNTB afferents with stimulation patterns that mimicked those present in vivo. We found that these semi-natural stimulation patterns reliably elicited a novel form of long-term potentiation (LTP) of MNTB-LSO synapses. Stimulation patterns that lacked the characteristic high-frequency (200 Hz) component of prehearing spike activity failed to elicit potentiation. LTP was calcium dependent, required the activation of both g-protein coupled GABAB and metabotropic glutamate receptors and involved an increase in postsynaptic glycine receptor-mediated currents. Our results provide a possible mechanism linking spontaneous spike bursts to tonotopic map refinement and further highlight the importance of the co-release of GABA and glutamate from immature glycinergic MNTB terminals.

Highlights

Before the onset of hearing, cochlea-generated patterns of spontaneous spike activity drive the maturation of central auditory circuits
In this study we demonstrate that semi-natural stimulation patterns that mimic the temporal structure of spontaneous activity in vivo before hearing onset elicit a novel form of inhibitory glycinergic long-term potentiation (LTP) in the developing medial nucleus of the trapezoid body (MNTB)-lateral superior olive (LSO) pathway in vitro
The topographic precision of the MNTB-LSO pathway is increased by the silencing of most initial connections and the strengthening of maintained ones[11,12,13,15]

Summary

Introduction

Before the onset of hearing, cochlea-generated patterns of spontaneous spike activity drive the maturation of central auditory circuits. The high degree of precision of the tonotopic organization of the glycinergic MNTB-LSO pathway in mature animals is not present at early developmental stages but emerges gradually by processes that involve the silencing of most initial MNTB-LSO connections and the strengthening of maintained ones[10,11,12,13,14,15] In altricial rodents, such as mice, rats, and gerbils, this refinement occurs during the first two postnatal weeks and during a time when MNTB-LSO synapses exhibit a number of transient properties such as acting as excitatory rather than inhibitory synapses due to a high intracellular chloride concentration in LSO neurons[16,17,18,19,20] or the co-release of GABA and Scientific Reports | (2020) 10:16899. Despite its important role in the maturation of central auditory circuits, the synaptic and cellular mechanism by which patterned spike activity mediates the refinement of tonotopic maps has remained poorly understood

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