“
“The prefrontal cortex (PFC), with its

abundant anatomical interconnections with numerous other cortical and subcortical areas, is thought to play a key role in the integration of information from different brain regions to support various cognitive functions (Fuster, 2001 and Miller and Cohen, 2001). In particular, the PFC is thought to be a pivotal substrate for maintaining information in the absence of changing XAV-939 solubility dmso external inputs, and neuronal activity in this brain region is assumed to be critical in working memory (Goldman-Rakic, 1995 and Baddeley, 2003). It has been suggested that the PFC works in synergy with other brain regions, including basal ganglia and the hippocampus, in order to implement memory-related activity (Fuster, 2001 and Miller and Cohen, 2001). It has been shown that recruitment of memory-active neurons in the PFC depends on task-relevant dopamine release from the ventral tegmental area (VTA) neurons (Williams and Goldman-Rakic, 1995, Watanabe et al., 1997, Lewis and O’Donnell, 2000 and Schultz, 2006). Another synergistic mechanism of the PFC that interacts with other brain regions is implied by electroencephalogram (EEG) studies in humans. These experiments have demonstrated that the

power of EEG oscillations in the 3–7 Hz band, recorded from the scalp above the PFC area (called “midline frontal theta”), correlates with working-memory performance (Gevins et al., 1997 and Sauseng et al., 2010). In human studies, it has been tacitly assumed that the midline frontal theta rhythm is generated by the hippocampus (Klimesch et al., 2001, Canolty PD-1/PD-L1 inhibitor 2 et al., 2006 and Fuentemilla et al., 2010). In support of this hypothesis, recent experiments in rodents have shown increased phase coupling between hippocampal theta oscillations (7–9 Hz) and PFC neuronal firing during the working-memory aspects of spatial tasks (Siapas et al., 2005, Jones and Wilson,

2005, Benchenane et al., 2010 and Sigurdsson et al., 2010). However, theta frequency oscillations in the PFC are conspicuously weak or absent (Siapas et al., 2005, Jones and Wilson, 2005 and Sirota et al., 2008), and it is unclear how the mesolimbic dopaminergic system is involved in hippocampal-PFC else coordination (Benchenane et al., 2010 and Lisman and Grace, 2005). Despite recent progress, the mechanisms underlying the temporal coordination of cell assemblies in the PFC-VTA-hippocampal system have remained ambiguous (Lisman and Grace, 2005). In this study, we performed simultaneous large-scale recordings of neuronal activities and local field potentials in the medial prefrontal cortex (mPFC), the VTA, and the hippocampus of the rat during a working-memory task. We found that a 4 Hz (2–5 Hz band) oscillation is dominant in PFC-VTA circuits and is phase coupled to hippocampal theta oscillations when working memory is in use. Both local gamma oscillations and neuronal firing can become phase locked to the 4 Hz oscillation.