Here then is a destination potentially connected to a couple of waypoints. Perhaps

these oscillatory and sleep disturbances reflect an underlying neurobiological dysfunction that could be trans-isomer dissected in detail. As a starting point, the authors chose to examine, using the MAM-E17 rat model, whether and how a disruption of embryonic brain development might lead to sleep disturbances and to further examine the neural activity patterns underlying these disturbances. The MAM-E17 model evolved from early studies on the effect of methylazoxymethanol (MAM), a naturally occurring nucleic acid alkylating agent (Smith, 1966), on the developing brain. An early study (Haddad et al., 1969) showed that administration of MAM to pregnant rat dams resulted in alterations in brain structure and behavior in the offspring, including Capmatinib supplier microcephaly, hyperactivity, and apparent learning deficits. Although not entirely selective, MAM can be used to target specific circuits through

ontological timing of the exposure (Rice and Barone, 2000). Offspring of dams exposed to appropriate doses of MAM at embryonic day 17 (E17) exhibit neuropathological, neurochemical, and behavioral phenotypes that appear analogous, in some cases homologous, to phenotypes reported in schizophrenia (see Lodge and Grace, 2009 for review). MAM-E17 leads to an apparent reduction in neuropil in frontal and temporal cortex and a decrease in the density of parvalbumin-expressing (PV+) cortical

interneurons, two histopathological findings reported in schizophrenia (Lodge and Grace, 2009). Finally, adult MAM E17 offspring show a schizophrenia-relevant array of cognitive deficits including deficits in sensorimotor gating, latent inhibition, and cognitive flexibility (Featherstone et al., 2007; Lodge and Grace, mafosfamide 2009; Moore et al., 2006). These and other findings support the use of this model to examine plausible, mechanistic links between neural and behavioral phenotypes of relevance to schizophrenia. Along this line, Phillips et al. (2012) exemplifies a novel and powerful approach. Taking the MAM-E17 model as a starting point, the authors examine it from a novel perspective—that perhaps the cognitive deficits observed in this model (and, by extension, in schizophrenia) might be due to disruptions in sleep. To this end, they recorded cranial EEG and behavior from MAM-E17 offspring and controls, monitoring them around the clock. While the MAM-E17 rats showed the normal circadian rhythms, the amount of non-REM sleep was significantly reduced. Moreover, the EEG recordings demonstrated decreases in delta-frequency power in the posterior cranial site, due primarily to a decrease in the density of delta waves.