They found that mEPSC amplitudes were unchanged at 6 and 18 hr postlesion but then increased at

24 and 48 hr, closely matching the time course of activity rate homeostasis. Because spine size is correlated with synaptic strength, and changes in a predictable manner when circuits are weakened or strengthened in response to MD in vivo (Hofer et al., 2009), Keck et al. (2013) hypothesized that in vivo scaling of synaptic strengths should have a structural correlate in altered dendritic spine size. Remarkably, they indeed found that spine size on L5 pyramidal neurons increased 24 hr after the retinal lesion and was maintained at 48 hr, thus following the same time course as the changes in DAPT price mEPSC amplitude and cortical activity in vivo. Altogether, these data and those obtained by Hengen et al. (2013) are consistent with the hypothesis that synaptic scaling could underlie homeostatic adjustments in neocortical firing rates in vivo. The studies by Hengen et al. (2013) and Keck et al. (2013) provide much anticipated evidence supporting that neuronal activity levels are homeostatically regulated in the neocortex in vivo. While both studies report an initial drop in activity levels in response to sensory deprivation, followed by a subsequent rebound, the time courses of the

two observations are dramatically different. Interestingly, the rapid sensory deprivation induced drop in overall activity levels observed by Keck et al. (2013) recovered to control levels within 24 hr, which is when Hengen et al. (2013)

obtained their first measurements selleck chemicals llc also showing baseline firing rates in excitatory neurons. Discrepancies between the two studies are evident only at 48 hr, when Hengen et al. (2013) see significant depression of firing rates in excitatory neurons, whereas Keck et al. (2013) observe baseline activity Tryptophan synthase levels. Most likely, differences are due to the widely diverse experimental conditions in the two studies—including deprivation protocols (monocular lid suture versus binocular retinal lesion), species (rat versus mouse), and ages (juvenile versus adult; Figure 1). Future experiments utilizing similar paradigms, while independently varying the individual parameters, will shed light on the mechanisms and origins of these differences. Several testable predictions arise from these studies and lead to exciting new avenues of research. While these studies support that synaptic scaling could be responsible for homeostatic regulation of firing rates in the neocortex, they do not exclude that alternative mechanisms of synaptic plasticity, such as plasticity of intrinsic excitability, anti-Hebbian mechanisms, or Hebbian modifications of excitatory or inhibitory synapses, are also at play. One prediction is that a homeostatic set point should operate bidirectionally; and consequently, enhanced firing rates due to sensory overstimulation should be homeostatically downregulated.