Two major limitations of this study should be taken into account however, i.e. that the experiments were done under urethane anesthesia, and that the data obtained are mostly correlational. Thus, further investigations are necessary both under urethane and in awake animals to understand the mechanism and function of PFC-HC coupling. Besides the core findings on the novel 2–5 Hz rhythm supported by both partial correlation and pharmacology, there are several further observations in regard of theta coupling, which although premature to fully assess at this point may stimulate further investigations. First, we found non-zero residual PFC-HC (0.13, Fig 5E) and even PFC-nRE theta ( 0.42, Fig. 5E) correlation when controlling for the third signal. It should be noted in this regard that besides nRE, several other structures have reciprocal connections with PFC and HC (Fig. 7A) which were not recorded in this study, but might have been the origin of these residual correlations, These include the amygdala (AMY), supramammillary nucleus (SUM), entorhinal cortex (EC), medial septum (MS), and (VTA) (McKenna and Vertes 2004; Cassel et al. 2013; Dolleman-Van der Weel
