Pre- and postsynaptic properties of glutamatergic transmission in the immature inhibitory MNTB-LSO pathway

Abstract

The lateral superior olive (LSO) integrates excitatory inputs driven by sound arriving at the ipsilateral ear with inhibitory inputs driven by sound arriving at the contralateral ear in order to compute interaural intensity differences needed for localizing high-frequency sound sources. Specific mechanisms necessary for developmental refinement of the inhibitory projection, which arises from the medial nucleus of the trapezoid body (MNTB), have only been partially deciphered. The demonstration that immature MNTB-LSO synapses release glutamate has led to a model in which early glutamate neurotransmission plays a major role in inhibitory plasticity. We used whole cell electrophysiology in acute auditory brain stem slices of neonatal rats to examine glutamatergic transmission in the developing MNTB-LSO pathway. Unexpectedly, AMPA receptor (AMPAR)-mediated responses were prevalent at the earliest ages. We found a salient developmental profile for NMDA receptor (NMDAR) activation, described both by the proportion of total glutamate current and by current durations, and we found evidence for distinct release probabilities for GABA/glycine and glutamate in the MNTB-LSO pathway. The developmental profile of NMDAR is consistent with the possibility that the inhibitory MNTB-LSO pathway experiences a sensitive period, driven by cochlear activity and mediated by GluN2B-containing NMDARs, between postnatal days 3 and 9. Differing neurotransmitter release probabilities could allow the synapse to switch between GABA/glycinergic transmission and mixed glutamate/GABA/glycinergic transmission in response to changing patterns of spiking activity.