, 2008; Hardingham et al., 2008), it is unlikely

that a change in NMDARs has caused the increase in surround STD-LTP in our study. Similar to LTP, surround potentiation in the barrel cortex is dependent on αCamKII autophosphorylation (Glazewski U0126 in vitro et al., 2000). The addition of synapses could also increase the susceptibility to LTP and thereby contribute to the expansion of barrel cortex receptive fields (Cheetham et al., 2008; Hardingham et al., 2011; Wilbrecht et al., 2010). In addition, deprivation unmasks a PKA-dependent plasticity mechanism that facilitates STD-LTP in deprived barrel columns in vitro (Hardingham et al., 2008), or elicits mGluR-mediated metaplasticity in a singly spared barrel column (Clem et al.,

2008). We cannot exclude that such changes in connectivity or postsynaptic molecular machinery contributed to the facilitation of STD-LTP of SW-evoked responses in our study. However, our finding that a GABA-A-R block did not on average enhance the levels of SW-driven STD-LTP RG7420 concentration after DWE as compared to the nondeprived barrel cortex (Figure 8) strongly suggests that disinhibition was at least an important contributing factor to DWE-mediated STD-LTP facilitation. In conclusion disinhibition-mediated facilitation of STD-LTP is likely to represent a form of metaplasticity that supports the experience-dependent fusion and expansion of receptive fields upon partial sensory deprivation. All procedures were performed according protocols approved by the ethics committee of the University of Geneva and the authorities of the canton of

Geneva. Young adult C57Bl/6 male mice (postnatal day [P] 21–P51) were used. Control and deprived (DWE) mice were from the same litters. Experiments on control mice (n = 33; average weight, 13.4 ± 4 g) and deprived mice (n = 28; average weight, 14.1 ± 3 g; p = see more 0.2) were interleaved. All mice were housed in a moderately enriched environment (some tunnels and climbing racks were provided). For DWE all except the C1 and C2 whiskers on the left side of the snout were trimmed daily under light isoflurane anesthesia to keep the whisker stumps shorter than 2 mm. On the right side of the snout, all whiskers were trimmed. Experiments were performed after 2–4 days of DWE (mean deprivation time, 2.4 ± 0.9 days, n = 28). For control mice all except the C1 and C2 whiskers were trimmed under anesthesia just prior to the experiment. Mice were first anaesthetized with isoflurane (4% for induction with ∼0.5 l/min O2) and then with urethane (1.5 g/kg, i.p., prepared in lactated ringer solution containing 102 mM NaCl, 28 mM Na L-Lactate, 4 mM KCl, 1.5 mM CaCl2). Eye ointment was applied to prevent dehydration. The scalp was locally anesthetized with lidocaine (1%), the periosteum gently removed, and a custom-made plastic chamber was attached to the skull above barrel cortex (centered 1.