’s investigation of the temporal dynamics of eye-position gain fields

in the lateral intraparietal find more area (LIP) pushes us one step closer to understanding the role gain fields can—and cannot—play in neural computation. “
“The past decade has seen tremendous advances in the genetics of autism spectrum disorders (ASDs). Rapidly evolving genomic technologies combined with the availability of increasingly large study cohorts has led to a series of highly reproducible findings (Betancur, 2011; Devlin et al., 2011; Devlin and Scherer, 2012), highlighting the contribution of rare variation in both DNA sequence and chromosomal structure, placing limits on the risk conferred by individual, common genetic polymorphisms, underscoring the role of de novo germline mutation, suggesting

a staggering degree of genetic heterogeneity, demonstrating the highly pleiotropic effects of ASD-associated mutations, and identifying, definitively, an increasing number of specific genes and chromosomal intervals conferring risk. This progress marks a long-awaited emergence of the field from a period of tremendous uncertainty regarding viable approaches to gene discovery. At the same time, the findings underscore the scale of the challenges ahead. Twin studies have consistently identified a significant genetic component of ASD risk (Hallmayer et al., 2011; Ronald and Hoekstra, 2011) and gene discovery dates back over a decade (Betancur, 2011; Devlin and Scherer, 2012). Recent analyses demonstrate that common polymorphisms carry substantial risk for ASD (Anney et al., 2012; Klei et al., 2012). However, common polymorphisms have so far proven difficult to identify selleck screening library and replicate, probably because the relative risk conferred by these loci is small and cohort sizes have not yet reached those found necessary to identify common polymorphisms contributing to other complex

psychiatric disorders (Devlin et al., 2011). In contrast, a focus on rare Topotecan HCl and de novo mutation has already been highly productive in uncovering an appreciable fraction of population risk and identifying variation conferring relatively larger biological effects. An example of the considerable traction provided by a focus on rare inherited and de novo variation can be found in the earliest successes in ASD genetics. The protein products of risk genes for patients ascertained with nonsyndromic ASD, including NLGN4X, NRXN1, and SHANK3, colocalize at the postsynaptic density in excitatory glutamatergic synapses with those coded for by genes first identified in syndromic subjects, including FMRP, PTEN, TSC1, and TSC2 (note, however, that as gene identification continues, “syndromic” genes are being identified in nonsyndromic cases and vice versa). These results are cause for optimism with regard to the prospects for identifying treatments that will have efficacy well beyond the boundaries suggested by mutation-defined subgroups.