, 2001). Furthermore, the mutated calcineurin gene (PPP3CC) has been shown to map to chromosomal loci previously implicated in schizophrenia by genetic linkage studies ( Gerber et al., 2003). Taken together, these features suggest that the calcineurin KO provides a unique opportunity to investigate the neural basis of UMI-77 cell line dysfunction in a schizophrenia model. The hippocampus is a brain structure critical for episodic memory (Gaffan, 1994, Olton and Samuelson, 1976, Scoville and Milner, 1957 and Steele and Morris, 1999) and spatial learning (Morris et al., 1982 and O’Keefe and Nadel, 1978). In freely moving rodents, the hippocampus

exhibits distinct activity profiles dependent on behavioral state (Buzsáki, 1989), suggesting distinct modes of information processing within the structure. During running, the hippocampal electroencephalogram (EEG) exhibits a 4–12 Hz theta rhythm (Skaggs et al., 1996), and hippocampal

principal neurons exhibit location-specific responses, known as place fields, as reported in rats (O’Keefe and Dostrovsky, 1971), mice (McHugh et al., 1996), monkeys (Matsumura et al., 1999), and humans (Ekstrom et al., 2003). By contrast, during awake rest periods, hippocampal EEG is distinguished by sharp-wave-ripple (SWR) events (Buzsáki, 1989) and hippocampal principal neurons take part in extended sequences of coactivity, which replay previous behavioral episodes Enzalutamide datasheet (Davidson et al., 2009, Diba and Buzsáki, 2007, Foster and Wilson, 2006 and Gupta et al., 2010) as well as preplay subsequent behavioral episodes (Dragoi and Tonegawa, 2011, Dragoi and Tonegawa, 2013 and Pfeiffer and Foster, 2013). There is substantial evidence linking schizophrenia with damage to the hippocampus (Weinberger, 1999). Dysfunction of the hippocampus and related medial temporal lobe structures has also been reported in schizophrenia patients (Small

et al., 2011), together with selective impairments in learning and memory. In addition, abnormal brain activity in schizophrenia patients has been detected in various brain structures, including mafosfamide the hippocampus, during rest periods (Buckner et al., 2008) and during passive task epochs (Harrison et al., 2007). Since the pattern of impairments of calcineurin KO mice—synaptic plasticity changes in the hippocampus and hippocampal-dependent behavioral phenotypes such as working memory—suggested that hippocampal function might be affected in this mouse model of schizophrenia, we targeted the hippocampus for electrophysiological recordings in freely behaving KO and littermate controls (CT) and investigated changes in information processing during exploratory behavior and resting periods. To characterize hippocampal activity in our mouse model, we employed microdrives with multiple independently adjustable tetrodes to record single-unit spikes and EEG from the CA1 subregion of the dorsal hippocampus of freely behaving KO mice (n = 7) and floxed littermate CT (n = 5).