, 1983). Phase shifts could also arise from a single pacemaker (e.g., medial septum) through delays emerging from a chain of unidirectionally linked groups of neurons (Ermentrout and Kleinfeld, 2001). Another mechanism that could provide delays would be a chain of oscillators residing within the pacemaker itself (e.g., the septal area) and the phase shift observed in the hippocampus would be a reflection of the phase-delayed septal outputs. While this latter solution

cannot be fully excluded, it would require a complex temporal coordination of the hippocampal and entorhinal neurons in different regions and layers with appropriate delays. We hypothesize that traveling theta waves arise from a network of “weakly coupled” (Kopell and Ermentrout, 1986) intrahippocampal Lumacaftor ic50 and matched entorhinal cortex see more oscillators. In support of this hypothesis,

both the CA3 recurrent system and in vitro slices of the CA3 region can generate theta oscillations (Konopacki et al., 1987; Kocsis et al., 1999). In addition, delays with similar magnitudes documented here have been reported in the isolated CA3 region in vitro (Miles et al., 1988). The importance of weakly coupled oscillators in traveling waves is illustrated by the spinal cord activity of the lamprey during swimming (Kopell and Ermentrout, 1986; Cohen et al., 1992). The swim rhythm arises from intersegmental coordination of spinal cord oscillators, connected by local connections with short delays. The dominance of forward swimming is secured by the faster oscillators in the frontal end of the cord (Grillner et al., 1995). By analogy, the oscillation frequencies of place cell assemblies decrease progressively along the septotemporal axis of the hippocampus (Jung et al., 1994; Maurer et al., 2005; Kjelstrup et al., 2008; Royer et al., 2010) and theta oscillating cell

groups are coupled by delays (Geisler et al., 2010). Similarly, the oscillation frequencies of medial entorhinal cortex neurons decrease progressively in the dorsoventral direction (Giocomo et al., 2007), providing a frequency match between corresponding of entorhinal and hippocampal neurons. Due to the delays, the faster but transient assembly oscillators produce a slower global rhythm, expressed by the coherent LFP oscillation in the entire length of the hippocampus and entorhinal cortex (Geisler et al., 2010). The progressively decreasing excitability of pyramidal neurons along the long axis (Segal et al., 2010) might further contribute to the dominantly septotemporal spread of activity. Finally, septally projecting long-range interneurons (Dragoi et al., 1999; Tóth et al., 1993; Jinno et al.