, 1992). This controversy may be explained by the co-occurrence of two rhythms in the PFC, as shown here. In human studies, it is often

tacitly assumed that the “cognitive frontal rhythm” (Klimesch et al., 2001) is driven by hippocampal theta oscillations (Jensen and Tesche, 2002). Alternatively, it may be more related to the 4 Hz oscillations described here. In support of this hypothesis, several studies have pointed out that the behavioral specificity of fm-theta depends on the frequency band chosen (Klimesch et al., 2001, Onton et al., 2005 and Sauseng find more et al., 2010). Finally, recent studies in primates suggest that resetting of LFP in this low frequency band plays an important role in attention and stimulus ZVADFMK selection (Lakatos et al., 2008). We hypothesize that, similar to our observations in the PFC of the rat, two distinct oscillations with complementary roles are activated during working memory in the human prefrontal cortex and other mammals. Structures within the limbic area and basal ganglia form distinct systems and perform different types of computations. However, systems often interact to support various behaviors. The representation strengths of memories and planning (served by PFC-hippocampus circuits) are often strongly affected by associated values (served by basal

ganglia circuits; Luo et al., 2011). The various structures of the limbic system are bound together functionally by theta oscillations (Buzsáki, 2002). Our findings, along with previous observations by others, suggest that activity in the basal ganglia is temporally coordinated by a 4 Hz oscillation. We hypothesize that the phase-phase (2:1) coupling mechanism between theta and 4 Hz oscillations provides

a communication link between the limbic and basal ganglia systems (Figure 8). Theta and 4 Hz oscillations can exert cross-structure, cross-frequency phase-coupling effects on local operations, as reflected by the comodulation of gamma power by these slower rhythms. In our experiments, the cross-frequency phase coupling effectively modulated task-specific PFC neurons, which carried goal-related positional and memory information. These findings illustrate how three independent rhythms (i.e., 4 Hz, theta, and gamma) can coalesce transiently to perform Terminal deoxynucleotidyl transferase specific actions. We hypothesize that phase coupling between the 4 Hz and theta oscillators, and their joint modulation of local gamma oscillations, may be a mechanism for linking the entorhinal-hippocampal spatial-contextual system with the mesolimbic dopaminergic reward system. All protocols were approved by the Institutional Animal Care and Use Committee of Rutgers University. Seven adult male (3–5 months old) rats were trained in an odor-based delayed match-to-sample working-memory task prior to surgery. The training apparatus was a figure eight T maze with a start area, in which the sample odors (chocolate or cheese) were presented and goal arms contained the reward.