Taken together, the EEG findings are consistent with deficits in long-range coordination of the oscillations that define non-REM sleep. Of course, the strength of an animal model is the ability to move beyond EEG recordings to examine specific circuits within the brain. Accordingly, combined hippocampal and medial prefrontal cortical depth recordings uncovered deficits in the synchrony that normally occurs within this circuit

during non-REM sleep. Specifically, hippocampal ripples (150–250 Hz bursts in the CT99021 cost local field potential) are typically tightly correlated with the occurrence of spindles in the prefrontal cortex (Siapas and Wilson, 1998). Phillips et al. (2012) report a decrease in the synchronization of spindles and ripples in MAM-E17 rats, as well as a decrease in the synchrony between prefrontal cortical and hippocampal single unit firing patterns. Veliparib ic50 Simply put, MAM-E17 rats show a loss of limbic-cortical synchrony. How might these findings relate to schizophrenia symptomatology? The authors suggest that this disruption in limbic-cortical interactions disorganizes the normally tightly orchestrated slow wave and ripple/spindle oscillations, reducing the extent of non-REM

sleep. Referring to the substantial literature implicating these oscillatory sleep phenomena in cognitive processes such as consolidation, they then speculate that such a disruption may contribute to the cognitive dysfunction seen in the disease. While the current manuscript does not directly compare disruptions in cognition and sleep in the MAM-E17 rats, the authors note that clinical studies suggest a correlation between reductions in non-REM sleep and cognitive performance

in patients with very schizophrenia (Manoach and Stickgold, 2009). From a mechanistic standpoint, the findings described here are intriguing, as they provide a framework for future studies into the specific mechanisms by which disruptions in neurodevelopment can alter the fidelity of sleep-related neural oscillations. In their discussion, Phillips et al. (2012) point to one possible mechanism: PV+ interneurons. The apparent density of these interneurons is decreased in both schizophrenia patients and MAM-E17 rats. Moreover, they have been implicated in the generation of cortical oscillations of various frequencies (Gonzalez-Burgos et al., 2011). Exploring the role of PV+ interneurons in delta-, ripple-, and spindle-frequency oscillations and their coordination during non-REM sleep would be a promising future endeavor. Another potential mechanistic path to explore would be the role of long-range connections in the observed physiological and behavioral phenotypes. Indeed, while the authors demonstrate some disruption of local processes, such as a subtle decrease in spindle density, the most striking findings relate to synchrony across regions.