, 2002 and Levitin et al., 2008), α3 (Arredondo et al., 2006), and α7 (Chimienti et al., 2003, Levitin et al., 2008 and Hruska et al., 2009) nAChR subtypes; some interactions actually enhance nicotinic responses (Chimienti et al., 2003 and Levitin et al., 2008), or their Ca2+ components (Darvas et al., 2009). The actions of lynx family proteins manifest themselves at both circuit (Hruska et al., 2009) and network levels (Pfeffer et al., 2009) on nicotinic systems. The blunting effect of lynx proteins

could be responsible for the paucity of synaptically driven nicotinic responses recorded in brain tissue despite the rich cholinergic innervation, as well as the different response properties in brain tissue find protocol as compared with heterologous expression systems (Quick and Lester, 2002). Removal of the molecular brake provided by lynx proteins can lead to nicotinic receptor hypersensitivity—larger direct nicotinic responses, slowed desensitization kinetics (Miwa et al., 2006), BIBW2992 and enhanced sensitivity of the EPSC frequency in the cortex

to nicotine (Tekinay et al., 2009). As a consequence of nAChR hypersensitivity, lynx1 knockout mice display increased levels of Ca2+ in neurons, enhancements in synaptic efficacy, and improved learning and memory functions (Miwa et al., 2006, Darvas et al., 2009 and Tekinay et al., 2009). Studies on such hyperactive nicotinic receptors can reveal cholinergic-dependent processes with increased clarity. For instance, adult lynx1KO mice display heightened ocular dominance plasticity after the normal close of the critical period (Morishita et al., 2010). While the role of the cholinergic system during visual processing (Disney

et al., 2007) and development has been appreciated (Bear and Singer, 1986), it has been a mystery why the critical period closes in late postnatal development and remains closed despite heavy cholinergic why innervation of the visual system. These findings indicate that suppression of the cholinergic system by lynx proteins stabilizes neural circuitry. Indeed, cholinergic enhancement (via cholinesterase inhibition) reopens the critical period for visual acuity in adult wild-type mice (Morishita et al., 2010), indicating that cellular mechanisms for robust plasticity are maintained in adulthood through the cholinergic system but are suppressed by the action of lynx. Abolishing receptor function through null mutations or pharmacological blockers of nAChRs abolished some of the gain-of-function phenotypes in lynx mouse models, indicating that nAChRs are necessary for the expression of lynx perturbations (Miwa et al., 2006). This indicates that lynx proteins exist, genetically, as upstream modulators of nicotinic receptor function and cholinergic signaling and can exert control over cholinergic-dependent processes. Because excess activation of nAChRs damages neuronal health and brain function, organisms have a clear need to restrict the degree of nAChR activation.