, 2011 and Marder and Goaillard, 2006). Potentially substantiating the latter possibility, we find that long-day entrainment increases the level of PER2::LUC expression within the SCN core, which suggests that this condition induces changes in cellular and/or network signaling. The mechanistic bases, biological relevance, and state dependence

of these forms of SCN plasticity warrant further study. After reorganization, SCN core and shell neurons resynchronize to reestablish a steady-state network organization, which indicates that these SCN compartments are coupled through bidirectional lines of communication. Since most studies have found anatomical connections traveling only from the SCN core to shell neurons, this study provides the best evidence to date for the functional transmission 3-MA cost of information in the opposite direction. First, we found that VIP signaling contributes to network synchronization in both steady-state Selleckchem EPZ-6438 and reorganized states, which confirms and extends previous work using genetic models deficient in VIP signaling. Because VIP

is produced exclusively by neurons within the SCN core, VIP in this context likely acts as a cue transmitted from the SCN core to the SCN shell. Thus, this result indicates the presence of another coupling signal transmitted from the shell that directly resets SCN core neurons. We then tested whether GABAA Carnitine palmitoyltransferase II signaling might serve this role, since GABA is synthesized and processed in nearly

all SCN neurons (Abrahamson and Moore, 2001 and Belenky et al., 2008). We found that GABAA signaling contributes to network resynchronization when the SCN network is in an antiphase state, but not in less polarized states. This further indicates that at least one other signal is transmitted from the shell to reset SCN core neurons and produce network resynchronization in less polarized states. Given the lack of compelling evidence for synaptic connections from shell to core neurons, this yet-to-be-identified signal may be paracrine in nature (Maywood et al., 2011 and LeSauter and Silver, 1998). Further use of this functional coupling assay has the potential to reveal additional aspects of SCN circuitry that would be difficult to detect with the exclusive use of loss-of-function genetic models. In addition to the common developmental confounds associated with germline mutations, murine models lacking VIP or GABAA signaling display deficits in photic entrainment and resetting (Han et al., 2012, Dragich et al., 2010 and Hughes et al., 2004), which can limit the utility of these models to investigate the specific role of these factors in intrinsic network coupling. The use of a genetically intact model in this study circumvented these issues and allowed us to exploit light-induced changes in network organization to investigate the functional roles of VIP and GABAA signaling in SCN coupling.