Abstract
The vesicular glutamate transporter 3 (VGLUT3) is expressed at several locations not normally associated with glutamate release. Although the function of this protein has been generally elusive, when expressed in non-glutamatergic synaptic terminals, VGLUT3 can not only allow glutamate co-transmission but also synergize the action of non-glutamate vesicular transporters. Interestingly, in the immature glycinergic projection between the medial nucleus of the trapezoid body (MNTB) and the lateral superior olive (LSO) of auditory brainstem, the transient early expression of VGLUT3 is required for normal developmental refinement. It has however been unknown whether the primary function of VGLUT3 in development of these inhibitory synapses is to enable glutamate release or to promote loading of inhibitory neurotransmitter through vesicular synergy. Using tissue from young mice in which Vglut3 had been genetically deleted, we evaluated inhibitory neurotransmission in the MNTB-LSO pathway. Our results show, in contrast to what has been seen at adult synapses, that VGLUT3 expression has little or no effect on vesicular synergy at the immature glycinergic synapse of brainstem. This finding supports the model that the primary function of increased VGLUT3 expression in the immature auditory brainstem is to enable glutamate release in a developing inhibitory circuit.
Highlights
The glycinergic projection from the medial nucleus of the trapezoid body (MNTB) to lateral superior olive (LSO) is a critical component of the neural circuit for localizing higher frequency sound sources
If the vesicular synergy model holds true in the immature MNTB-LSO pathway, we would expect differing levels of Vglut3 to correlate with differences in GABA/glycinergic transmission, in particular for measures of short-term plasticity, recovery from short-term depression, and quantal size
We predicted that quantal size and the amplitude of miniature synaptic events would be larger at MNTB-LSO synapses expressing vesicular glutamate transporter 3 (VGLUT3)
Summary
The glycinergic projection from the medial nucleus of the trapezoid body (MNTB) to lateral superior olive (LSO) is a critical component of the neural circuit for localizing higher frequency sound sources (for review, see Tollin, 2003, though see Jalabi et al, 2013). The MNTB-LSO pathway, with its precise, tonotopically organized circuitry and well-defined inputs, has been a model system for understanding inhibitory circuit refinement, the mechanisms of this synaptic refinement have yet to be elucidated, in part because immature MNTB-LSO synapses exhibit a complex neurotransmitter phenotype. As is common at other immature glycinergic synapses, MNTB terminals in the LSO use GABA transmission (Kotak et al, 1998; Nabekura et al, 2004), for unknown reasons (Gillespie and Kandler, 2009). Due to the transient expression of vesicular glutamate transporter 3 (VGLUT3), MNTB terminals release glutamate during the first postnatal week (Gillespie et al, 2005), a period characterized by major synaptic refinement (Kim and Kandler, 2003). The precise role of VGLUT3 in this refinement has not been elucidated
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