Investigation of NMDA Receptor Subunit Composition in the Developing Cat Visual System Following Brief Immersion in Darkness

Abstract

During early postnatal development, the critical period is a time during which the visual system exhibits robust plasticity, and neural circuitry can be easily modified by changing levels of visually-driven activity. Although the exact mechanisms of critical period plasticity are unknown, the subunit composition of the N-methyl-D-aspartate (NMDA) receptor is a putative mechanism for experience-dependent plasticity. The composition of the receptor is thought to mediate plasticity by modifying the threshold of activity needed to induce long-term potentiation and long-term depression, thus altering the likelihood of synaptic strengthening and weakening. The current study aimed to provide further insight into the role of the NMDA receptor composition in experience-dependent plasticity. This study employed a novel multiplex immunolabeling method to quantify NMDA receptor subunits composition in tissue slices from cat dorsal lateral geniculate nucleus (LGN) and primary visual cortex (V1). The method used in this study preserved in situ protein distribution within both regions, and therefore, allowed for an investigation into layer-specific changes in receptor composition. In order to assess how activity levels alter the NMDA receptor composition, animals were exposed to a 10-day period of darkness to eliminate visually-driven activity. We found that dark exposure altered NMDA receptor subunit composition in both the LGN and V1, shifting the composition towards its neonatal isoform in a universal manner. We also observed a significant reduction in neuron soma size in both the LGN and V1, which indicates that darkness may stall development or revert the brain to a more immature state. Together these results indicate that the NMDA receptor subunit composition is a potential mechanism of darkness mediated plasticity because the change in receptor composition produced by darkness predicts that the modification threshold would favour synaptic strengthening.