The mechanisms responsible for the generation of theta activity in the MTL are complex and not entirely understood (see e.g., Buzsáki, 2002). One original hypothesis is that cholinergic excitation from the medial septum and the diagonal band of Broca activates inhibitory interneurons, which in turn induce rhythmic IPSPs on the soma of pyramidal cells (Petsche et al., 1962). More recent data from rodent hippocampal slice preparations and in anesthetized rats indicate that theta activity can also be generated intrinsically in the CA1 region of the hippocampus (Gillies et al., 2002; Rotstein et al., 2005) and the parasubiculum (Glasgow and Chapman, 2007). Analyses of hippocampal recordings in awake rats have provided evidence for at least two hippocampal theta rhythms of which only one is mediated by inputs from the entorhinal cortex (Kocsis et al., 1999). Although lesion studies in rodents have shown a strong influence of entorhinal inputs on hippocampal theta activity (Bragin et al., 1995; Buzsaki et al., 1983; Kamondi et al., 1998), to our knowledge, no direct comparison between entorhinal and hippocampal theta activity has been reported in animals or humans to date.
