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

Content Provider	PubMed Central
Author	Hauser, Jessica L. Edson, Eleanore B. Hooks, Bryan M. Chen, Chinfei
Copyright Year	2013
Abstract	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.
Related Links	http://dx.doi.org/10.1152/jn.00897.2012
Ending Page	123
Page Count	11
Starting Page	113
File Format	PDF
ISSN	00223077
e-ISSN	15221598
Journal	Journal of Neurophysiology
Issue Number	1
Volume Number	109
Language	English
Publisher	American Physiological Society
Publisher Date	2013-01-01
Access Restriction	Open
Rights Holder	American Physiological Society
Subject Keyword	Physiology Neuroscience(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience Physiology

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