, 1998, Vinje and Gallant, 2000, Fiser et al., 2004, Iurilli et al., 2012 and Keller et al., 2012). Specifically, neuronal activity in the visual cortex has been shown to be both modulated (Niell and Stryker, 2010, Andermann et al., 2011 and Ayaz et al., 2013) and driven (Keller et al., 2012) by locomotion of the animal. To verify that the observed drop in average cortical activity was not simply the result of a decrease in overall motor activity after visual deprivation, we examined cortical activity levels during episodes of locomotion. Indeed, changes in activity levels followed the same overall trend (decreased activity at 6 hr, increasing

at 24–48 hr) during locomotion (Figures S1F and S1G). Furthermore, we measured the fraction of time that the animals spent running before MDV3100 and after lesions. We found no difference between lesioned animals and sham-lesioned controls (Figure S1H), except at 6 hr postlesion when lesioned animals were more active than sham-lesioned animals yet had lower cortical activity levels. These results show that the changes in cortical http://www.selleckchem.com/products/GDC-0449.html activity are caused by removal of retinal input rather than reduced locomotion. Having observed a recovery in activity

levels in visual cortex, we next investigated whether established mechanisms of homeostatic plasticity were underlying these changes. We thus performed whole-cell recordings from layer 5 pyramidal neurons in acute slices prepared from visual cortex of adult animals at 6, 18, 24, and 48 hr after complete retinal lesions. We measured amplitude and frequency of mEPSCs and found that mEPSC amplitude was not changed relative to sham-lesioned controls either 6 or 18 hr after a complete retinal lesion (Figure 2A). In line with previous

results from cortical cultures (Turrigiano et al., 1998) and from layer 4 (Desai et al., 2002) and layer 2/3 cells (Desai et al., 2002, Goel et al., 2006 and Maffei and Turrigiano, 2008, but see Lambo and Turrigiano, 2013) in visual cortex slices, there was a significant increase in the amplitude 24–48 hr (Figures PAK6 2A and 2B) after silencing both retinae, indicating an increase in the strength of excitatory synapses. We noted a transient decrease in mEPSC frequency 18 hr after input removal (Figure 2C), which is consistent with reduced cortical activity measured with GCaMP at 18 hr after lesioning (Figure 1). There was, however, no significant change before or after that time point (Figures 2C and 2D). The increase in mEPSC amplitude 24–48 hr after deprivation parallels the changes in activity observed in vivo, suggesting that synaptic scaling contributes to the changes in cortical activity.