Abstract
Before hearing onset, the topographic organization of the inhibitory sound localization pathway from the medial nucleus of the trapezoid body (MNTB) to the lateral superior olive (LSO) is refined by means of synaptic silencing and strengthening. During this refinement period MNTB-LSO synapses not only release GABA and glycine but also release glutamate. This co-released glutamate can elicit postsynaptic currents that are predominantly mediated by NMDA receptors (NMDARs). To gain a better understanding of how glutamate contributes to synaptic signaling at developing MNTB-LSO inhibitory synapses, we investigated to what degree and under what conditions NMDARs contribute to postsynaptic calcium responses. Our results demonstrate that MNTB-LSO synapses can elicit compartmentalized calcium responses along aspiny LSO dendrites. These responses are significantly attenuated by the NMDAR antagonist APV. APV, however, had no effect on somatically recorded electrical postsynaptic responses, indicating little, if any, contribution of NMDARs to spike generation. NMDAR-mediated calcium responses were decreased when increasing extracellular magnesium concentrations to physiological levels indicating that MNTB-LSO synapses activate magnesium sensitive NMDAR on immature LSO dendrites. In Fura-2 AM loaded neurons, blocking GABAA and glycine receptors increased NMDAR contribution to somatic calcium responses suggesting that GABA and glycine, perhaps by shunting backpropagating action potentials, decrease the level of NMDAR activation under strong stimulus conditions.
Highlights
Interaural sound intensity differences are a major cue by which animals determine the azimuth position of incoming sound
To gain a better understanding of how glutamate contributes to synaptic signaling at developing medial nucleus of the trapezoid body (MNTB)-lateral superior olive (LSO) inhibitory synapses, we investigated to what degree and under what conditions NMDA receptors (NMDARs) contribute to postsynaptic calcium responses
Our results show that MNTB-LSO synapses can elicit compartmentalized Ca2+ responses in aspiny LSO dendrites and that NMDARs significantly contribute to these Ca2+ responses
Summary
Interaural sound intensity differences are a major cue by which animals determine the azimuth position of incoming sound. LSO neurons become functionally disconnected from about 75% of their initial MNTB inputs while maintained connections become about 10-fold stronger (Kim and Kandler, 2003; Noh et al, 2010) Concurrent with this period of refinement, the properties of synaptic transmission at MNTB-LSO synapses show a number of developmentally transient features. MNTB-LSO synapses release both the traditional inhibitory neurotransmitters, glycine and GABA (Kotak et al, 1998; Nabekura et al, 2004), and the traditional excitatory neurotransmitter, glutamate (Gillespie et al, 2005) This glutamate co-release is crucial for the topographic refinement of the MNTB-LSO pathway. Our results show that MNTB-LSO synapses can elicit compartmentalized Ca2+ responses in aspiny LSO dendrites and that NMDARs significantly contribute to these Ca2+ responses
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