Slow NMDA-Mediated Excitation Accelerates Offset-Response Latencies Generated via a Post-Inhibitory Rebound Mechanism

Ezhilarasan Rajaram, Carina Kaltenbach, Matthew J Fischl, Leander Mrowka, Olga Alexandrova, Benedikt Grothe, Matthias H Hennig, Conny Kopp-Scheinpflug

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

In neural circuits, action potentials (spikes) are conventionally caused by excitatory inputs whereas inhibitory inputs reduce or modulate neuronal excitability. We previously showed that neurons in the superior paraolivary nucleus (SPN) require solely synaptic inhibition to generate their hallmark offset response, a burst of spikes at the end of a sound stimulus, via a post-inhibitory rebound mechanism. In addition SPN neurons receive excitatory inputs, but their functional significance is not yet known. Here we used mice of both sexes to demonstrate that in SPN neurons, the classical roles for excitation and inhibition are switched, with inhibitory inputs driving spike firing and excitatory inputs modulating this response. Hodgkin-Huxley modeling suggests that a slow, NMDA receptor (NMDAR)-mediated excitation would accelerate the offset response. We find corroborating evidence from in vitro and in vivo recordings that lack of excitation prolonged offset-response latencies and rendered them more variable to changing sound intensity levels. Our results reveal an unsuspected function for slow excitation in improving the timing of post-inhibitory rebound firing even when the firing itself does not depend on excitation. This shows the auditory system employs highly specialized mechanisms to encode timing-sensitive features of sound offsets which are crucial for sound-duration encoding and have profound biological importance for encoding the temporal structure of speech.

Original languageEnglish
Number of pages20
Issue number3
Early online date31 May 2019
Publication statusPublished - 4 Jun 2019

Keywords / Materials (for Non-textual outputs)

  • auditory development
  • duration encoding
  • gap-detection
  • level-tolerance
  • sound-offset encoding
  • superior paraolivary nucleus


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