| Abstract No.: | B-A2002 |
| Country: | Canada |
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| Title: | EXPRESSION OF NOVEL CA2+ PERMEABLE AMPA RECEPTORS IN THE DEVELOPING RETINA IS TRIGGERED BY NEUROTROPHINS
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| Authors/Affiliations: | 1 Ingrid Osswald*; 1 Alba Galan; 1 R. Anne McKinney; 1 Derek Bowie;
1 McGill University, Montreal, QC, Canada
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| Content: | Early sensory experience is crucial to the development and maturation of synaptic circuits. In the retina, plastic changes in neuronal circuits have been mainly reported for excitatory ganglion cells. In this cell-type, light-deprivation (LD) interferes with normal dendritic modeling that in turn compromises visual processing. Importantly, Ca2+ influx through NMDA-selective ionotropic glutamate receptors has been shown to be central to this process. However, not all retinal cells express NMDARs. Recently we have identified a novel philanthotoxin (PhTX)-insensitive Ca2+-permeable AMPAR (CP-AMPAR) that is developmentally-regulated and selectively expressed in two inhibitory retinal cells, horizontal cells (HC) and A2 amacrine cells. Interestingly, neither cell-type expresses synaptic NMDARs suggesting that Ca2+-influx through novel AMPARs may be also important for dendritic refinement. Here, we show that light entering the eye shapes inhibitory synaptic circuit formation by triggering expression of a novel CP-AMPAR. Using cobalt (Co2+) staining and electrophysiological recordings to examine the expression of CP-AMPARs, we observed that PhTX-insensitive receptors failed to express in dark-reared animals. Interestingly, BDNF protein levels were almost completely abolished in light-deprived rats suggesting that light entering the eye triggers expression of novel CP-AMPARs through a BDNF-dependent pathway. Consistent with this, exogenous application of BDNF (250 nM, 1 hr) rescued PhTX-insensitivity in dark-reared rats. Finally, dendritic arborization of A2 cells in light–deprived retinae was disordered compared to control. Moreover, immunohistochemical studies using recoverin and PKC antibodies, specific markers for OFF-cone bipolar cells and rod-bipolar cells, respectively, showed that the more distal portion of the dendritic arbor was disrupted in dark-reared rats. In summary, the neurotrophin BDNF triggers a novel CP-AMPAR that may be critical to sculpting retinal circuits. |
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