In line with this hypothesis, we have previously reported—using the same deprivation paradigm—that the turnover of spines, which is typically associated with synapse specific (or nonhomeostatic) plasticity (Trachtenberg et al., 2002, Zuo et al., 2005 and Holtmaat et al., 2006), increases 72 hr after deprivation (Keck et al., 2008).

Taking these data together, we suggest the following scenario: immediately after a complete lesion of both retinae, cortical activity decreases to approximately half the original value. Synaptic scaling then manifests itself after 24 hr, at which time mEPSC amplitudes and spine sizes have increased, followed by a decrease in inhibition after 48 hr. The overall increase

in synaptic strength, together with a reduction in inhibition, leads to a nearly complete restoration of cortical activity levels; however, selleck chemical feedforward inputs NVP-BKM120 order are not restored. Thus, after 72 hr, dendritic spine turnover increases (Keck et al., 2008), potentially reflecting the search for novel active inputs and further circuit rearrangement. An extended description of the experimental procedures is included in the Supplemental Experimental Procedures. All experimental procedures carried out at the Max Planck Institute of Neurobiology were performed in accordance with the institutional guidelines of the Max Planck Society and the local government DNA ligase (Regierung

von Oberbayern). All experimental procedures carried out at the Friedrich Miescher Institute in Basel were approved by the Veterinary Department of the Canton of Basel-Stadt, Switzerland. Complete retinal lesions were carried out as described previously (Keck et al., 2008). At 6, 18, 24, or 48 hr after the retinal/sham lesion, coronal slices were prepared from C57BL/6J mice. Visualized whole-cell patch-clamp recordings of layer 5 pyramidal neurons were performed at room temperature (24°C). mEPSCs or mIPSCs were recorded in voltage clamp at −70 mV (corrected for liquid junction potential). mEPSC and mIPSC analysis was done with custom software, blind to the experimental condition. Events were detected based on amplitudes greater than 5 pA and 20%–80% rise times of less than 1 ms (Desai et al., 2002). Experiments were carried out as described previously (Keck et al., 2008). Cranial windows were implanted (Holtmaat et al., 2009) in adult mice expressing enhanced GFP (eGFP) under the thy-1 promoter (GFP-M line [ Feng et al., 2000]). The visual cortex was localized using intrinsic signal imaging prior to retinal lesions. Apical dendrites in layer 1 and 2/3 (0–150 μm below the pial surface) of layer 5 cells in monocular visual cortex were imaged using a custom-built two-photon laser-scanning microscope.