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NMDAR-Mediated Calcium Transients Elicited by Glutamate Co-Release at Developing Inhibitory Synapses

  • Kalmbach, Abigail1, 2
  • Kullmann, Paul H. M.1
  • Kandler, Karl1, 2, 3
  • 1 Department of Neurobiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
  • 2 Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, USA
  • 3 Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA
Published Article
Frontiers in Synaptic Neuroscience
Frontiers Research Foundation
Publication Date
Jul 07, 2010
DOI: 10.3389/fnsyn.2010.00027
  • Neuroscience
  • Original Research


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.

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