Here, we extend these previous results, showing spindle phase locking of hippocampal ripple power similar to that reported in humans (Clemens et al., 2011) in SHAM animals (Figure 3). Embedded slow-wave, spindle, and ripple oscillations therefore coordinate the rhythmic firing of pyramidal cells in cortex and CA1, providing windows of opportunity for cross-structural synaptic plasticity. Indeed, oscillatory activity in both hippocampus and neocortex during NREM sleep is associated with selective reactivation of activity sequences seen during previous behaviors (Peyrache et al., 2009; O’Neill et al., 2010). The initiation of this replay SNS-032 solubility dmso through cortical delta wave-modulated

input may mark the beginning of a looped circuit interaction, whereby cortical delta waves initiate hippocampal reactivation during ripples, which in turn triggers cortical reactivation during spindles (Marshall and Bortezomib Born, 2007). The lack of coupling between hippocampal ripples and cortical spindles in MAM-17 rats demonstrates the crucial role of synchronized cortical slow-waves in organizing the dialog between cortex and hippocampus by providing

a temporal framework for faster oscillations. Disrupting this dialog presumably constitutes the neurophysiological mechanism for behavioral deficits in long term learning and memory described in the MAM E17 model (Flagstad et al., 2004; Gourevitch et al., 2004; Moore et al., 2006), and may contribute to cognitive deficits in other models of sleep fragmentation (Tartar et al., 2006). Our study serves to emphasize that disrupted thalamic-cortical-limbic network activity during sleep must therefore be considered alongside waking activity as a therapeutic

Phosphoprotein phosphatase target in schizophrenia and related diseases. Since active entrainment of slow-waves through transcranial stimulation enhances both spindle density and declarative memory in humans (Marshall et al., 2006) one intuitive possibility would be to use transcranial stimulation as a possible therapy for relieving cognitive and sleep deficits found in patients. The MAM-E17 model provides a unique opportunity to study the detailed cellular, synaptic and network mechanisms that underpin such novel therapeutic approaches. All procedures were carried out in accordance with the UK Animals Scientific Procedures Act (1986) and University of Bristol and Lilly UK ethical review. Sprague-Dawley dams were obtained from Charles River (UK) on day 12 of gestation and injected on E17 with saline or MAM (22 mg/kg i.p.; Midwest Research Institute, Missouri). Fifteen saline-injected and 15 MAM-injected dams produced 51 SHAM and 49 MAM pups. No more than two animals used were derived from a single litter. In brief, 70–80 day old rats were prepared for either EEG recording (cranial implant of five stainless steel screws: 2× motor cortex +3.9 mm AP, ± 2.0 mm ML, 2× visual cortex −6.4mm AP, ±5.