Visual-mediated regulation of retinal CaMKII and its GluR1 substrate is age-dependent

Abstract

Previous studies have shown that multifunctional calcium/calmodulin-dependent protein kinase II (CaMKII) and one of its substrates, the glutamate receptor, are key players in experience-driven synaptic plasticity in several areas of the central nervous system (CNS). To determine if CaMKII and the glutamate receptor are regulated by visual activity in the retina, we compared dark-reared (DR; 1 week) rats with control rats raised in a diurnal light–dark cycle (LD), at the following ages: postnatal day 12 (P12d), 2-month (2m) and 6-month (6m) old. The mRNA levels of CaMKIIα and β were determined by a competitive reverse transcription polymerase chain reaction (competitive RT-PCR) method. The protein levels of these two subunits were evaluated by immunoblots. The data show that the mRNAs for CaMKIIα and β were increased about 8-fold and 10-fold, respectively, in the retinae of DR P12d rats. As for the proteins, 2- and 2.6-fold elevations for CaMKIIα and β, respectively, were evident. The GluR1 subunit of the AMPAR (AMPAR-GluR1) was also evaluated in antibody-treated blots and found to be increased about 2-fold after 1 week of dark rearing in the retinae of P12d rats. This type of experience-driven molecular change was age-dependent, showing less increase in 2m old rats and not present in 6m old rats. Returning DR 2m old rats to the LD environment for 1 week was sufficient to restore the dark-induced changes to the levels of the age-matched LD controls. Based on the data, a theoretical model for activity-dependent modulation of the developing retinal synapses is proposed.