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Ben Stafford, Kwoon Wong, Jonathan Demb; Developmental changes in subunit- and pathway-specific expression of NMDA receptors in direction-selective ganglion cells. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4568.
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© ARVO (1962-2015); The Authors (2016-present)
Activity-dependent mechanisms regulate the formation of neural circuits in the retina. For example, bipolar cells (BCs) release glutamate onto AMPA and NMDA receptors (NMDARs) on the dendrites of ganglion cells (GCs), and reducing this release alters the number of synapses formed between BCs and GCs. In the cortex, the subunit composition of NMDARs regulates different aspects of synapse formation. In the retina, it is not known whether NMDARs composed of specific subunits are present at GC synapses during development, where they could regulate synapse formation. Here, we characterized developmental changes in the subunit composition of NMDARs that encode ON and OFF inputs onto genetically-identified ON-OFF direction-selective GCs (dsGCs).
We employed two transgenic mouse lines (Drd4 and TRHR) in which GFP labels ON-OFF dsGCs that are tuned for posterior motion (Huberman et al. 2009; Rivlin-Etzion et al. 2011). At P14 and P28, whole-cell, voltage-clamp recordings were made from GFP+ GCs at P14 and P28 in the ventral retina. Each cell was voltage-clamped at a series of holding potentials and, at each potential, a ~2mm-diameter UV (365-nm) stimulus was presented. To isolate glutamatergic inputs onto dsGCs, all recordings were made in the presence of 20µM gabazine (GABAA antagonist) and 200µM hexamethonium (nicotinic antagonist). To determine subunit specificity, we also recorded responses in the presence of ifenprodil (10 µM), an antagonist specific for NMDARs containing the GluN2B subunit.
At P14, NMDA-mediated responses were recorded in both light-ON and light-OFF responses, reflecting inputs from the ON and OFF pathways, respectively. Both pathways showed sensitivity to ifenprodil, with responses in the OFF pathway reduced more than those in the ON pathway. At P28, NMDA-mediated responses could still be elicited; however, responses in both pathways were unaffected by ifenprodil.
Our findings indicate that functional NMDARs are expressed at synapses between dsGCs and both ON and OFF BCs between P14 and P28. They further suggest that, at P14, OFF dendrites of dsGCs express GluN2B-containing NMDARs, while ON dendrites express GluN2A-containing NMDARs. This pathway-specific expression of GluN2A- and GluN2B-containing NMDARs suggests that these subunits might play different roles in synaptogenesis in the inner retina as they do in the cortex.
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