Therefore, regulation of lynx function that would allow the sensitivity of the cholinergic system to shift in response to environmental changes would be critical. Selleck IBET151 Partial, transient, or local reductions in lynx function may produce an optimal balance; moderate cholinergic signaling would enhance synaptic plasticity, yet still protect against hyperactivation that could make neurons susceptible to excitotoxic damage. What, then, regulates the regulator? Evidence thus far indicates that the lynx family is regulated

in response to relatively strong perturbations: downregulation in NKCC1 knockout mice (Pfeffer et al., 2009), in adenylyl cyclase mutant mice (Wieczorek et al., 2010), and by α7 nAChR blockade (Hruska et al., 2009), whereas it is upregulated at the close of the critical period in the visual cortex, and by nicotine in the lung (Sekhon et al., 2005). Through functionally driven regulation of lynx expression, cholinergic systems have the ability to exert top-down www.selleckchem.com/screening/ion-channel-ligand-library.html influences on circuits underlying relevant behavior via coordinated regulation of nicotinic receptors subsets. While genetic linkages of lynx family members to neurological disorders

have not been found, evidence for cholinergic dysregulation has been linked to a lynx family member expressed in nonneuronal tissues and involved in human disease (Chimienti et al., 2003), and as such, alterations in lynx dosage may be useful in ameliorating cognitive decline associated with neuropsychiatric disorders. The synaptic tuclazepam pruning of neuronal circuits takes place late in the developing brain, after a period of early sculpting of neuronal number through programmed cell death. Nicotinic receptor systems have been implicated at both these stages and evidence suggests an involvement with lynx prototoxins as well. For instance, early expression

of lynx1 family member, PSCA, prevents programmed cell death of parasympathetic neurons (Hruska et al., 2009). Neuronal maturation and loss of synaptic lability appear to be correlated with the onset of lynx1 expression. In the majority of cases, circuit stability would provide an adaptive advantage once sculpting of circuitry has been influenced by the patterned activity of experience. Temporal coherence of information is critical for creating a stable internal representation of our environment and provides the background for salient information to reach our attention. But what happens in cases when that program goes awry? Lynx1 is downregulated in NKCC1 KO mice (Pfeffer et al., 2009), a strain that has a delayed developmental program of GABAergic neurons, diminished inhibition, and less spontaneous network activity. The neurodevelopmental program depends in part on α7 signaling (Liu et al., 2006).