Arc (activity regulated cytoskeleton-associated protein), also known as Arg3.1, is an immediate early gene and is considered to play a critical role in synaptic plasticity. However, its contribution to plasticity of specific cell types within intact cortical circuits is unknown. Using optical imaging of intrinsic signals, we have previously reported that Arc knock-out mice show impaired ocular dominance plasticity (McCurry et al., Nature Neuroscience 13: 450, 2010). However, Arc is only expressed in excitatory neurons in the visual cortex. Here, we report on the plasticity of cells which do and do not express Arc, employing Arc-GFP mice, in which GFP is expressed under the control of the Arc promoter. Using GFP expression as a marker for excitatory neurons, we classified neurons into GFP-positive (putative excitatory) and GFP-negative (putative inhibitory) neurons. At around the peak of critical period (P27-29), we performed monocular deprivation (MD) in heterozygote and homozygote Arc-GFP mice. After 5-6 days of MD, we loaded cells with the calcium indicator dye OGB1 and used functional two-photon calcium imaging to measure eye-specific visual responses and calculate the ocular dominance index (ODI) of individual neurons. In heterozygote mice, GFP marks cells that contain Arc; these mice showed a shift of the ODI in both GFP-positive and GFP-negative neurons. In homozygote mice, in which GFP marks precisely those cells that lack Arc, there was no significant ODI shift of GFP-positive neurons, demonstrating impaired plasticity. GFP-negative neurons, however, showed a significant ODI shift, indicating plasticity in inhibitory neurons independent of excitatory neurons. We are currently investigating whether short-duration MD also has differential effects on putative excitatory and inhibitory neurons.

Society for Neuroscience Abstract, 2010.