Conditional mGluR5 Knockout in Glutamatergic Pathways Disrupts the Development of Excitatory Synaptic Transmission onto Mouse MNTB Neurons

Metabotropic glutamate receptor 5 (mGluR5) plays a pivotal role in neurodevelopment. Here, we investigated the consequences of mGluR5 loss-of-function on the development of glutamatergic transmission onto the medial nucleus of the trapezoid body (MNTB). Using the Cre-loxP system, we generated a conditional knockout (KO) mouse line in which mGluR5 expression was selectively eliminated in vesicular glutamate transporter 2 (VGluT2)-expressing glutamatergic pathways, including the calyx of Held synapse innervating MNTB neurons. Whole-cell patch-clamp recordings from mice of either sex at postnatal days 30–38 were used to compare the excitatory synaptic properties of MNTB neurons between KO mice and wild type controls. Upon afferent stimulation of the trapezoid body, MNTB neurons exhibited two distinct types of evoked EPSCs (eEPSCs): large calyceal all-or-none and smaller non-calyceal responses. In mGluR5 KO mice, there was a significant increase in the proportion of neurons exhibiting non-calyceal eEPSCs. The calyceal all-or-none eEPSCs showed significantly prolonged latency, along with slower kinetics in both eEPSCs and asynchronous EPSCs. Analysis of short-term synaptic plasticity of the non-calyceal eEPSCs revealed an increased paired-pulse ratio in mGluR5 KO mice. Additionally, membrane capacitance was significantly reduced, consistent with a smaller somatic area in mGluR5 KO mice. These results suggest that mGluR5 plays a critical role in shaping the excitatory synaptic properties necessary for fast temporal processing in the MNTB.