In early reports in the behaving rats, researchers at The Laboratory for Behavioral Neuroscience identified neurons of the nucleus pontis oralis (RPO) of the brainstem with activity that was highly correlated with the theta rhythm of the hippocampus in waking and REM sleep. They further showed that RPO stimulation generated theta and that stimulation of the median raphe nucleus (MR) desynchronized the hippocampal EEG (Vertes, 1981). These findings indicated a critical role for RPO and MR in hippocampal synchronization (theta) and desynchronization, respectively.

They subsequently demonstrated that the supramammillary nucleus (SUM) of the hypothalamus represents a critical relay between RPO and the septum/hippocampus in the generation of theta. It was shown that:

With respect to MR, they have shown that: