Experience‐dependent refinement of the inhibitory axons projecting to the medial superior olive

Abstract

Neurons in the medial superior olive (MSO) analyze interaural time differences (ITDs) by comparing the arrival times of the two excitatory inputs from each ear using a coincidence detection mechanism. They also receive a prominent inhibitory, glycinergic projection from the ipsilateral medial nucleus of the trapezoid body (MNTB), which contributes to the fine-tuning of ITD analysis. Here, we investigated developmental changes of the axonal arborisation pattern of single Microruby-labeled MNTB neurons projecting to the MSO region. During the first 2 weeks after hearing onset, the axonal arborisation of MNTB neurons was significantly refined resulting in a narrowed projection area across the tonotopic axis of the MSO and a redistribution of the axonal endsegments to a mostly somatic location. Rearing the animals in omnidirectional noise prevented the structural changes of single MNTB projections. These results indicate that the functional elimination of inhibitory inputs on MSO neurons after hearing onset, as described previously, is paralleled by a structural, site-specific refinement of the inputs and is dependent on the normal acoustic experience of the animal.

Functional localization of neurotransmitter receptors and synaptic inputs to mature neurons of the medial superior olive

“…This finding is surprising in light of previous anatomical findings suggesting a synaptic refinement of inhibitory inputs (Kapfer et al 2002;Werthat et al 2008). This invariance may indicate that the mature functional GlyR gradient (biased toward the soma and proximal dendrites) is already established in the MSO at this age.…”

“…Anatomically, the developmentally driven restriction of inhibitory inputs to the soma and proximal dendrites of MSO neurons is well documented (Couchman et al 2010;Kapfer et al 2002;Kuwabara and Zook 1992;Werthat et al 2008). To date, though, there has been no functional investigation to confirm this morphological arrangement.…”

“…Glutamatergic excitation is dendritically targeted and mediated by AMPA receptors (AMPARs) (Clark 1969;Kil et al 1995;Smith et al 1993;Stotler 1953), while the inhibitory input is glycinergic (Brand et al 2002;Pecka et al 2008;Smith et al 2000) and targets the soma and proximal dendrites ( Fig. 1A) (Couchman et al 2010;Kapfer et al 2002;Kuwabara and Zook 1992;Werthat et al 2008). NMDA receptors (NMDARs) and GABA A Rs are thought to be synaptically activated only during early postnatal development and fully downregulated at mature synapses (Smith et al 2000).…”

Medial Superior Olivary Neurons Receive Surprisingly Few Excitatory and Inhibitory Inputs with Balanced Strength and Short-Term Dynamics

“…Together with the ultrastructural evidence for multiple release sites per synapse (Clark, 1969;Lindsey, 1975;Kiss and Majorossy, 1983;Brunso-Bechtold et al, 1990;Kapfer et al, 2002), this anatomically derived number matches well our physiological estimates of the number of presynaptic inhibitory release sites. Furthermore, we confirmed that one MNTB fiber innervates between 1 and 7 MSO neurons (Werthat et al, 2008).…”

“…Image stacks were processed with ImageJ, MetaMorph (Universal Imaging Corp., Visitron Systems GmbH), and Neurolucida (MBF Bioscience) to extract varicosity number and synaptic number by eye. For Figure 7 (see below), the acquired images were further processed in NIH ImageJ 1.37k (National Institutes of Health) as described by Werthat et al (2008). Individual cell processes visible on each optical section of MAP-2 staining were followed through the stack and labeled with the paintbrush tool.…”