Similarly, the decreased synchrony between hippocampal and prefrontal neural activity at both the

oscillatory activity and single unit levels suggests an impairment in long-range functional connectivity between these structures. The hypothesis that long-range connections are impaired in schizophrenia is an idea that has been gaining traction, most recently with the advent of functional and structural imaging techniques capable of examining connectivity in the intact human brain (Pettersson-Yeo et al., 2011). A key challenge has been to relate such findings Selleckchem isocitrate dehydrogenase inhibitor to specific etiological causes—to chart out the possible courses on the map. Here, progress is being made in a variety of ways. Deficits in connectivity have been linked to specific genetic mutations through both animal (Sigurdsson et al., 2010) and human (Esslinger et al., 2009) studies, as well as to an animal model of an environmental risk factor (Dickerson et al., 2010). The current study extends these findings to demonstrate deficits in functional connectivity in a toxin-induce model of a neurodevelopmental deficit that, as noted DAPT above, shares several neuropathological, neurochemical, and behavioral features with schizophrenia. Establishing

the relevance of these results from the MAM-E17 rat model to the neurobiology of schizophrenia will require further work. Beyond clarifying the mechanistic details, one key next step will be to examine sleep and sleep-related oscillations in animal models based on specific, known etiological factors, such as the 22q11 microdeletion or maternal infection models. Demonstrating similar findings in etiologically-relevant models will provide convergent validity, helping fill in the map of potential explanatory pathways. In addition, studies in such models will help address a principle limitation of the MAM-E17 model, which, though it shares

important features with schizophrenia, does not mimic any known specific cause of the disease. In the end, however, the utility of a model is not a function of how many features it shares with a disease, but rather how well it can be exploited to generate and test hypotheses about how that Histone demethylase disease arises and manifests in the brain. The Phillips et al. (2012) study suggests that neurodevelopmental disturbances can give rise to disturbances in the structure and quantity of non-REM sleep. It inspires the novel hypothesis that such disturbances might lead to the impaired cognitive function observed in schizophrenia. And it suggests specific, testable hypotheses for circuit-based mechanisms that might generate these disturbances. “
“Functional MRI has established itself as a cornerstone method of modern neuroscience research.