The potentiation of the inputs serving the nondeprived eye may be constrained in NARP−/− http://www.selleckchem.com/products/Y-27632.html mice by the absence of deprived eye depression, which has been proposed to be required to first lower the threshold for strengthening of synapses serving the nondeprived eye (Smith et al., 2009). There are important differences in the phenotype of the NARP−/− mouse from other transgenic models with deficits in ocular dominance plasticity. Transgenic manipulations that impair synaptic plasticity at excitatory synapses onto pyramidal neurons, such as deletion of the activity-regulated cytoskeletal protein arc, block the expression of ocular dominance plasticity along with a wide

range of other forms of homeostatic and Hebbian plasticity (McCurry et al., 2010). On the other hand, transgenic manipulations that result in hyperexcitability of the visual cortex, such as deletion of the synaptic isoform of the GABA synthetic enzyme GAD65, impair both GABAergic synaptic transmission (Choi et al., 2002) and the response to brief monocular deprivation

(Hensch et al., 1998). Nonetheless, slightly longer durations of monocular deprivation can reliably induce ocular dominance Olaparib shift in the visual system of GAD 65−/− mice (Fagiolini and Hensch, 2000). Ocular dominance plasticity is absent in NARP−/− mice, even in response to prolonged duration of monocular deprivation, suggesting that the visual cortex is unable to compensate for the absence of NARP. Nonetheless, several forms of experience-dependent synaptic plasticity, such as plasticity of the VEP contralateral bias and the response to high-frequency visual stimulation, are retained. The unique phenotype of the NARP−/− mouse underscores the importance of the recruitment of

fast inhibition, via regulation of excitatory drive onto FS (PV) INs, in the induction of fundamental forms of experience-dependent synaptic plasticity in the mammalian visual cortex. Wild-type and NARP−/− mice (Bjartmar et al., Metalloexopeptidase 2006) were of C57BL/6, 129/SVJII mixed genetic background. All subjects were raised on a 12 hr light/dark cycle, with food and water available ad libitum. All procedures conform to the guidelines of the U.S. Department of Health and Human Services and the Institutional Animal Care and Use Committees of the University of Maryland and Johns Hopkins University. Monocular deprivation was performed under ketamine/xylazine anesthesia (50 mg/10 mg/kg, i.p.). The margins of the upper and lower lids of one eye were trimmed and sutured together. The animals were returned to their home cages and disqualified in the event of suture opening or infection. Visual cortical slices (300 μm) were prepared as described (Huang et al., 2010) in ice-cold dissection buffer containing 212.7 mM sucrose, 5 mM KCl, 1.25 mM NaH2PO4, 10 mM MgCl2, 0.