Metabotropic glutamate receptors and glutamate transporters shape transmission at the developing retinogeniculate synapse

J Neurophysiol. 2013 Jan;109(1):113-23. doi: 10.1152/jn.00897.2012. Epub 2012 Oct 17.


Over the first few postnatal weeks, extensive remodeling occurs at the developing murine retinogeniculate synapse, the connection between retinal ganglion cells (RGCs) and the visual thalamus. Although numerous studies have described the role of activity in the refinement of this connection, little is known about the mechanisms that regulate glutamate concentration at and around the synapse over development. Here we show that interactions between glutamate transporters and metabotropic glutamate receptors (mGluRs) dynamically control the peak and time course of the excitatory postsynaptic current (EPSC) at the immature synapse. Inhibiting glutamate transporters by bath application of TBOA (DL-threo-β-benzyloxyaspartic acid) prolonged the decay kinetics of both α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-D-aspartate receptor (NMDAR) currents at all ages. Moreover, at the immature synapse, TBOA-induced increases in glutamate concentration led to the activation of group II/III mGluRs and a subsequent reduction in neurotransmitter release at RGC terminals. Inhibition of this negative-feedback mechanism resulted in a small but significant increase in peak NMDAR EPSCs during basal stimulation and a substantial increase in the peak with coapplication of TBOA. Activation of mGluRs also shaped the synaptic response during high-frequency trains of stimulation that mimic spontaneous RGC activity. At the mature synapse, however, the group II mGluRs and the group III mGluR7-mediated response are downregulated. Our results suggest that transporters reduce spillover of glutamate, shielding NMDARs and mGluRs from the neurotransmitter. Furthermore, mechanisms of glutamate clearance and release interact dynamically to control the glutamate transient at the developing retinogeniculate synapse.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Transport System X-AG / antagonists & inhibitors
  • Amino Acid Transport System X-AG / metabolism*
  • Animals
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Thalamus / drug effects
  • Thalamus / physiology*
  • Visual Pathways / drug effects
  • Visual Pathways / physiology*


  • Amino Acid Transport System X-AG
  • Excitatory Amino Acid Antagonists
  • Receptors, Metabotropic Glutamate