Experience-Dependent Regulation of NMDA Receptor Subunit Composition and Phosphorylation in the Retina and Visual Cortex

Abstract

Purpose. Experimental manipulation of experience during development can have profound effects on the functioning of the resulting circuits. N-methyl-d-aspartate glutamate receptor (NMDAR) activity is required for the establishment and refinement of neural circuits during development. In the present study, the authors addressed the issue of experience-dependent regulation of NMDARs by examining the effects of visual experience and deprivation on subunit composition and subunit phosphorylation of NMDAR in the retina and visual cortex. Methods. Total homogenates were prepared from retinas and visual cortices of 30-day-old (P30) Wistar rats, raised either in a normal 12-hour light/12-hour dark cycle (normal-reared [NR]) or in complete darkness from birth (dark-reared [DR]). Some of the DR animals were exposed to light for 6 hours at P30 (DR+6h). Immunoblotting was performed for the NMDAR subunits, NR2A and NR2B, and for the phosphorylated NR2B subunit protein at serine 1303 (pNR2B-Ser1303). Results. Dark rearing for 1 month decreased the NR2A/NR2B ratio and increased the level of phosphorylation of NR2B subunit at Ser1303 in the retina and visual cortex. Light exposure at P30 reversed the effects of visual deprivation on NMDAR composition and NR2B phosphorylation in both regions. Conclusions. These results indicated that NMDAR subunit composition and NR2B phosphorylation at Ser1303 is regulated bidirectionally by visual experience and deprivation in rat retina and visual cortex.

Age and Visual Experience-dependent Expression of NMDAR1 Splice Variants in Rat Retina

“…We and others have previously shown that dark rearing decreases NR2A and increases NR2B phosphorylation at serine 1303, with no change in NR2B protein levels in rat retina [42,43]. Therefore, taken together with the present results, it appears that visual experience can affect alternative splicing of the NR1 subunit in the retina in addition to NMDAR subunit composition and phosphorylation.…”

“…During retinal development, shortening of the NMDAR-mediated currents is observed in rat RGCs and this event is prevented by dark rearing the animals for 1 month [41]. Furthermore, modifications of retinal NMDAR subunit expression are observed during development and by dark rearing [28,[41][42][43]. In addition, visual experience regulates the development of retinal circuitry itself.…”

Synaptic protein interaction networks encode experience by assuming stimulus-specific and brain-region-specific states

“…However, measured biochemically, the level of diversity is less clear. Activation of CamKII ( Lisman et al, 2012 ), mobilization of SynGAP ( Araki et al, 2015 , 2020 ; Lautz et al, 2018 ) phosphorylation of NMDA receptors (NMDARs) ( Giannakopoulos et al, 2010 ; Rosenblum et al, 1996 ; Trepanier et al, 2012 ), and release of mGluR5 from Homer scaffolds ( Guo et al, 2015 ; Lautz et al, 2018 ; Ronesi et al, 2012 ) have been described for hippocampal or neocortical neurons, and likely occur elsewhere. However, the molecular rules that control plasticity may differ across brain areas; for example, at hippocampal synapses, kinase activation mediates long-term potentiation (LTP), whereas cerebellar LTP is mediated by phosphatase activation ( Belmeguenai and Hansel, 2005 ).…”

Synaptic signaling networks encode experience by assuming stimulus-specific and brain-region-specific states

“…However, measured biochemically, the level of diversity is less clear. Activation of CamKII [26], mobilization of SynGAP [27][28][29] phosphorylation of NMDARs [30][31][32], and release of mGluR5 from Homer scaffolds [29,33,34] have been described for hippocampal or neocortical neurons, and likely occur elsewhere. At a proteomic level, induction of long-term potentiation (LTP) in the hippocampus has been shown to alter the phosphorylation status of 570 sites across 220 postsynaptic proteins [35].…”