, 2007). However, examination of postmortem tissue and blood samples has so far yielded conflicting evidence for the presence of abnormalities in glutamatergic neurotransmission in ASDs (Markram and Markram, 2010). Data on gene expression levels support changes in GABA- and NMDA-receptor-mediated

neurotransmission in ASDs. Voineagu et al. (2011) examined gene-expression levels in frontal and temporal cortices of cases with ASDs and found alterations in genes that are involved in the regulation of interneurons, suggesting that the phenotype of ASDs is mediated by abnormal GABAergic neurotransmission. Similarly, mutations of the MeCP2 gene, which has been linked to a variety of neuropsychiatric disorders, including Rett-syndrome, autism, and childhood-onset schizophrenia, are associated with impaired GABAergic signaling in forebrain neurons and several behavioral features characteristic for ASDs, such as repetitive and impaired social behavior Vismodegib (Chao et al., 2010). Recently, Goffin et al. selleck chemicals llc (2012) furthermore showed that a mutation of the MeCP2 gene in mice leads to a reduction in amplitude and phase locking of event-related

oscillations at both low and high frequencies. The evidence reviewed suggests that there is substantial overlap between schizophrenia and ASDs with respect to deficits in neural synchrony and abnormalities in mechanisms supporting the generation of oscillations and synchrony. These indications for shared pathophysiological mechanisms are consistent with recent genetic data that have shown overlap between risk genes of both disorders (Guilmatre et al., 2009). However, there are also important differences between the two phenotypes, in particular in relation to the developmental periods at which the clinical symptoms emerge. ASDs are typically diagnosed during early childhood while schizophrenia typically manifests itself in late adolescence, raising the question which events determine these distinct time courses. In the following section, we will review recent evidence on fundamental changes in the E/I balance during development that might account for the distinct developmental

trajectories of ASDs and schizophrenia and provide cues for the development of effective treatments Adenosine (Figure 5). GABAergic neurotransmission is critically involved in the development of early cortical circuits and undergoes important modifications that in turn are fundamental for the temporal patterning of neuronal activity. GABA is the main inhibitory transmitter in the adult brain but during early development, GABA has an excitatory, depolarizing effect due to an altered chloride equilibrium and plays a central role in regulating cortical development (Ben-Ari et al., 1989; Luhmann and Prince, 1991; Wang and Kriegstein, 2009). PV interneurons that underlie the generation of high-frequency oscillations in the adult cortex are particularly important for the regulation of the time course of development and plasticity (Hensch, 2005).