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Ben Stafford, Kwoon Y. Wong, Jonathan B. Demb; Developmental Characterization Of NMDA Receptor Expression In Identified Retinal Ganglion Cells Of The Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6918.
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© ARVO (1962-2015); The Authors (2016-present)
Activity-dependent mechanisms play a crucial role in the development of neural circuits, and glutamatergic activity, encoded by AMPA and NMDA receptors, contributes to this process. NMDA receptors (NMDARs) are composed of multiple subunits, and, in the cortex, NMDARs composed of specific subunits can regulate the number and strength of excitatory synapses formed during development. In the retina, ganglion cells (GCs) express NMDARs and the subunit composition of NMDARs changes during development. However, it is not known whether the developmental shifts in NMDAR subunit expression occur in all GC types, or if the shift varies by cell type. Here, we tested the developmental expression of functional NMDAR subunits in 2 genetically-identified GC types.
Whole-cell, voltage-clamp recordings were performed in GCs at P7, P14, P21, and P28 in the whole-mount mouse retina. We employed two transgenic mouse lines (Drd4 and TRHR) which label two populations of ON-OFF direction selective GCs (dsGCs) that are tuned for posterior motion, but possess different directional tuning (Huberman et al. 2009 Neuron; Rivlin-Etzion et al. 2011 Neuron). We targeted GFP+ GCs and recorded responses to exogenous application of NMDA. To determine subunit specificity, responses were recorded under control conditions and in the presence of ifenprodil (10 µM), a GluN2B subunit specific NMDAR antagonist.
Drd4 and TRHR dsGCs demonstrated different developmental patterns of NMDAR expression. In Drd4 dsGCs, responses to NMDA application were reduced ~50% by application of ifenprodil at P7 and P14. However, by P21, responses to NMDA application in Drd4 dsGCs were unaffected by ifenprodil. In contrast, responses to NMDA application continued to be reduced by ~25% by ifenprodil in TRHR dsGCs until P28.
Our findings indicate that GluN2B containing NMDARs are expressed early in development before being down-regulated in adulthood in a cell-type specific fashion. Therefore, different GC types can possess different developmental NMDAR subunit expression profiles. Because both Drd4 and TRHR dsGCs respond to posterior motion, this suggests that GCs with similar functional properties might use NMDARs differently both during development and in the mature retina.
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