Reactivation of hippocampal ensemble firing occurs preferentially during CA1 sharp wave-ripples (O’Neill et al., 2010), which are in turn temporally correlated with thalamocortical sleep spindles (Siapas and Wilson, 1998; Sirota et al., 2003; Mölle et al., 2006); spindles themselves are phase locked to slow-waves and also associated with ensemble reactivation (Johnson et al., 2010). These temporal interrelationships may orchestrate

the induction of synaptic plasticity during sleep by aligning replay of ensemble activity during ripples and spindles with periods of high cortical excitability during slow-wave “up states” (Diekelmann Etoposide clinical trial and Born, 2010). However, circuit mechanisms of ripple-spindle coordination and their dependence on global sleep architecture have not been directly demonstrated. Given the interdependencies between neural activity during sleep and waking behavior, it is clear that sleep disruption may cause and/or exacerbate cognitive symptoms in diseases including schizophrenia,

depression, Parkinson’s, Alzheimer’s, and Huntington’s disease (Wulff et al., 2010). In particular, schizophrenia-associated deficits in attention and memory processing may be Veliparib nmr attributed to aberrant sleep-related consolidation mechanisms (Manoach and Stickgold, 2009) and therefore be reflected by altered neural activity during sleep. Reductions in the number and power of slow-waves (Keshavan et al., 1998; Göder et al., 2006) and reductions in sleep spindle density (Ferrarelli et al., 2010; Manoach et al., 2010; Keshavan et al., 2011) correlate with either baseline cognitive deficits (Göder et al., 2006) or deficits in overnight memory

recall (Göder et al., 2008; Manoach et al., 2010; Wamsley et al., 2012) in schizophrenia. These sleep abnormalities therefore constitute important targets for novel therapeutic intervention. The MAM-E17 rat neurodevelopmental model of schizophrenia (Moore et al., 2006) employs administration of a mitotoxin MAM (methylazoxymethanol-acetate) to pregnant rats to induce a neurodevelopmental disruption, selectively targeting limbic-cortical circuits by timing embryonic day 17 MAM injections Oxalosuccinic acid to coincide with hippocampal and prefrontal cortical embryogenesis (Lodge and Grace, 2009). Although no single intervention can model all aspects of schizophrenia in a rodent, the MAM-E17 model is therefore particularly useful in studying limbic-cortical dysfunction in neurodevelopmental disorders. MAM-E17 exposed rats show cognitive changes reminiscent of those seen in schizophrenia, including impairments in spatial working memory (Gourevitch et al., 2004), attentional set-shifting (Featherstone et al., 2007), and reversal learning (Moore et al., 2006). MAM-E17 exposed rats also harbor glutamatergic dysfunction (Hradetzky et al.