Importantly, lentiviral vector-mediated expression of the β2 subunit in prelimbic neurons completely restored the attention deficits, revealing a crucial role for β2 subunit-containing heteromeric channels in sustained attention [38]. In contrast to CSF-1R inhibitor β2-KO mice, mice lacking α5 subunits (α5-KO)

had decreased accuracy, but not a decreased omission rate in the 5CSRTT [39]. Nicotinic excitability in layer VI pyramidal neurons is reduced in α5-KO mice and eliminated in β2-KO, and muscarinic responses are enhanced in both β2-KO and α5-KO mice [40]. Thus, the imbalance of muscarinic and nicotinic excitation may in part account for the differential attention deficits in β2-KO and α5-KO mice [40]. α7-KO mice exhibit attention deficits and impulsivity in the 5CSRTT, although the

phenotypes could be paradigm-dependent 41, 38 and 42]. In an attention set-shifting task and a working memory test with CX-4945 in vitro a radial arm maze, α7-KO mice exhibit delayed procedural learning, which may be the central problem of developmental coordination disorders that are comorbid with ADHD [10]. Stergiakouli et al. argued for the role of α7 subunits based on copy number variation and genome-wide association studies using ADHD samples [43]. Fragile X syndrome (FXS), which is caused by the mutation in the X-linked gene FMR1, is the most inherited form of mental retardation and the leading cause of autism [44]. The majority of FXS patients, particularly boys, present with ADHD, and the ADHD symptoms represent a

significant problem for FXS patients [45]. FMR1 encodes fragile X mental retardation protein, an RNA-binding protein that regulates protein synthesis, and its lack in Fmr1-KO mice results in wide range of synaptic abnormalities, possibly via metabotropic glutamate receptor signaling pathways 44 and 46]. In the 5CSRTT, Fmr1-KO mice exhibit an increase in inaccurate responses and omission errors, suggesting attention ID-8 deficits, and an increase in premature responses, indicating impulsivity [47], although conflicting observations have also been reported [48]. It is noteworthy that these studies used mice with different genetic backgrounds. Fmr1-KO mice showed poor performance in an attention set-shifting task [49]. Interestingly, a role for Gmr5 is supported by findings from a human study [16••]. Actin is abundant in presynaptic and postsynaptic structures, and its dynamics have a central role in neuronal circuit development and activity-dependent plasticity 50 and 51]. Actin depolymerizing factor (ADF)/cofilin family members have essential roles in actin dynamics.