, 1999 and Di Cristo et al., 2007). Alternatively, plasticity at synapses that mediate feedback inhibition onto principle neurons in the visual cortex has been proposed to mediate the shift in ocular dominance induced by monocular deprivation (Maffei et al., 2006). Changes in interneuron excitability PD0332991 price and ocularity have been reported in response to monocular deprivation (Yazaki-Sugiyama et al., 2009, Gandhi et al., 2008 and Kameyama et al., 2010). Our work suggests that a critical step in

the initiation of the critical period is the recruitment of inhibition through NARP-dependent enhancement of excitatory drive onto FS (PV) INs. The deficit in the ability to recruit inhibition prevents the induction of ocular dominance plasticity in NARP−/− mice, despite the presence of normal perisomatic inhibition. Epigenetics inhibitor Importantly, sensory experience has been shown to strengthen excitation from thalamic afferents onto feed-forward inhibitory interneurons in layer IV of rodent barrel cortex (Chittajallu and Isaac, 2010), and in the visual cortex, these inputs are remodeled by monocular deprivation (Kuhlman et al., 2011). Monocular deprivation prior to the initiation of the critical period (∼P18 in rodents) is ineffective, demonstrating that a developmental change in visual cortical circuitry is necessary to initiate ocular dominance plasticity. In the

absence of NARP, the visual system is retained in a hyperexcitable state that is reminiscent of this precritical period. The method that we used to assess ocular dominance plasticity, examination of the contralateral bias of VEPs evoked by simple visual stimuli, may have lower threshold for the detection of changes induced by MD than other methods, such as change in visual acuity (Prusky and Douglas, 2003 and Heimel et al., 2007). In addition, our VEP recordings were performed in superficial layers of the visual cortex, where ocular dominance plasticity is expressed Casein kinase 1 long into postnatal development in wild-types (Fischer et al., 2007, Heimel et al., 2007, Lehmann and Löwel,

2008 and Sato and Stryker, 2008). Despite this, we saw no evidence for a shift in ocular dominance in NARP−/− mice, including in response to monocular deprivation of unusually long duration (>10 weeks). This suggests that the visual system cannot compensate for the absence of NARP and is unable to recruit the inhibition necessary to enable ocular dominance plasticity. Of course we cannot rule out the possibility that monocular deprivation in NARP−/− mice induces changes in the strength of synapses outside the recording radius of our electrode. Previous work has identified an important role for neuronal pentraxins in the refinement of retinogeniculate synapses in the dorsal lateral geniculate nucleus (dLGN) (Bjartmar et al., 2006).