Ultrastructural basis of strong unitary inhibition in a binaural neuron

Abstract

Binaural neurons in the lateral superior olive (LSO) integrate sound information arriving from each ear, and powerful glycinergic inhibition of these neurons plays an important role in this process. In the present study, we investigated the ultrastructural basis for strong inhibitory inputs onto LSO neurons using serial block face scanning electron microscopy. We reconstructed axon segments that make contact with the partially reconstructed soma and proximal dendrite of a mouse LSO neuron at postnatal day 18. Using functional measurements and the Sr method, we find a constant quantal size but a variable quantal content between 'weak' and 'strong' unitary IPSCs. A 3-D reconstruction of a LSO neuron and its somatic synaptic afferents reveals how a large number of inhibitory axons intermingle in a complex fashion on the soma and proximal dendrite of an LSO neuron; a smaller number of excitatory axons was also observed. A given inhibitory axon typically contacts an LSO neuron via several large varicosities (average diameter 3.7 μm), which contain several active zones (range 1-11). The number of active zones across individual axon segments was highly variable. These data suggest that the variable unitary IPSC amplitude is caused by a variable number of active zones between inhibitory axons that innervate a given LSO neuron. The results of the present study show that relatively large multi-active zone varicosities, which can be repeated many times in a given presynaptic axon, provide the ultrastructural basis for the strong multiquantal inhibition received by LSO neurons.

Specific synaptic input strengths determine the computational properties of excitation–inhibition integration in a sound localization circuit

“…; Hruskova et al . ), thus creating large quantal amplitudes (Kim & Kandler, ), and the elaboration of multiple active zones by inhibitory axons enabling the generation of multiquantal IPSCs (Gjoni et al ., ).…”

“…The number of repeated varicosities per axon, and therefore also the total number of active zones, strongly varied between individual axons. This, together with a constant quantal size between ‘small’ and ‘large’ unitary IPSCs estimated by the Sr 2+ method (Gjoni et al ., ), strongly suggests that ‘small’ and ‘large’ unitary IPSCs are primarily distinguished by the number of active zones that they establish with an LSO neuron. Furthermore, when studying younger LSO neurons with fibre stimulation, we found that the characteristic ∼10‐fold variation between inputs is already found at ∼P7, despite an overall weaker total inhibition strength in pre‐hearing mice (smaller maximal IPSCs; data not shown).…”

Optimal dissection of a model circuit

“…Gjoni et al . (, b ) have carried out an elegant analysis of synaptic integration at the neurons in the lateral superior olive (LSO). At this site, excitatory inputs and inhibitory inputs are received that originate from the ipsi‐ and and contralateral ears, respectively.…”

“…Gjoni et al . (, b ) addressed these questions by a combination of optogenetics, electron microscopy, model simulation and electrophysiology.…”

“…By introducing modern technology to address this classical physiological problem, the two papers by Gjoni et al . (, b ) have established a new quantitative approach to bridge synaptic physiology and neural circuit computation. The study is technically difficult, but the results are logical and impressive, setting a new standard for future research of synaptic integration.…”