Additional in vitro studies in slice preparations suggested that the SWS-induced potentiation of cortical responses is mediated by a calcium-dependent postsynaptic mechanism that requires coactivation learn more of AMPA and NMDA receptors, further corroborating the view of synaptic potentiation rather than downscaling induced by SWS. While the synaptic homeostasis hypothesis allocates such long-term potentiation (LTP)-mediated synaptic upscaling to the waking brain, neither in vivo nor in vitro recordings by Chauvette et al. revealed any hints that cortical responsiveness globally increases across the wake period. Interestingly, the upscaling of excitatory postsynaptic

potential responses observed after SWS-like stimulation patterns in vitro occurred only when the stimulation pattern included an intracellular hyperpolarizing current pulse mimicking the down phase of the slow waves. While the hyperpolarizing down phase of a slow wave has been considered a time framing signal resetting activity in extended cortical networks (e.g., Mölle and Born, 2011), this result is the first to indicate a functional significance specifically for the slow-wave down state for LTP. In showing that the slow waves of SWS can convey LTP-mediated synaptic upscaling, Chauvette et al.’s findings provide a neurophysiological basis for a rapidly growing body of

data indicating a particular role for SWS in memory consolidation (Diekelmann and Born, 2010). Cortical representations, corticostriatal representations, and episodic memory representations

extending over hippocampo-neocortical networks all appear to be enhanced by SWS (e.g., selleck kinase inhibitor Frank et al., 2001; Huber et al., 2004; Wilhelm et al., 2011), and a causal contribution of slow oscillations (∼0.75 Hz) has also been demonstrated (Marshall et al., 2006). Processes of sleep-dependent memory enhancement in these studies Phosphoprotein phosphatase could well incur the net upscaling of cortical networks mediated by postlearning SWS. However, Chauvette et al.’s findings appear to contradict the body of evidence arguing toward synaptic downscaling across sleep. For example, by measuring miniature excitatory postsynaptic currents, a valid indicator of synaptic scaling, Liu et al. (2010) showed signs of increased synaptic potentiation at the end of the wake period and reduced potentiation after sleep in rodent frontal cortex slices. Also, Vyazovskiy et al. (2008) showed that the slope and amplitude of cortical evoked responses to electrical stimulation were increased after wakefulness and decreased after sleep, with these changes correlating with changes in slow-wave activity. Moreover, amplitude and slope of slow waves, as well as the synchrony of cortical cell firing with slow waves, were found to decrease across periods of SWS (Vyazovskiy et al., 2009). Collectively, these and many other studies provide compelling evidence that there are global processes of synaptic downscaling at work during sleep.