It might suggest that the rat’s behavior is controlled or updated on a predefined time schedule. In the TGF-beta inhibitor maze, it is ambiguous whether theta power fluctuations occurring at specific time points and locations are due to intrinsic or external, behaviorally driven factors because of the stereotypic behavior of the animal in this task, generating confounding correlations among time, space, and behavior (such as the animal systematically initiating movement at the start location, turning at the T junction, slowing down before turn and reward

locations). But on the other hand, TPSM was also robustly expressed in situations in which animals are not expected to follow stereotypic trajectories (open field) or were steadily running for several seconds without interruption (wheel), as well as in REM sleep during which the absence of sensory-motor and behavior-related processing favors the expression of endogenously generated brain patterns. Altogether, these results represent strong evidence for the presence of an endogenous rhythmic modulation of theta power in the hippocampal circuit, potentially reflecting Palbociclib cell line the temporal organization of sensory-motor processes. While similarities between awake and REM-sleep theta activity have been proposed

to result from the replay of awake activity during sleep (Louie and Wilson, 2001), the alternative hypothesis that endogenously generated sequences of activity might be played again during awake behavior (preplay) has recently received experimental support (Dragoi and Tonegawa, 2011). A daring hypothesis is therefore that awake theta power fluctuations and their behavioral correlates are influenced by rhythmic cycles of brain activity in the 0.5–1 Hz range, the endogenous nature of which is suggested by their expression during sleep, in absence of ongoing behavior. Further work will

be necessary to decipher the relative influences of endogenous and external factors in the modulation of theta power and behavior. Recording the EEG and neuronal discharge of multiple individually through identified hippocampal neurons, we have observed that the endogenous, rhythmic fluctuations of theta power, also provided a temporal reference for neuronal population firing on a time scale of about 1.3 s. During sleep, most modulated neurons displayed a marked preference for the TPSM phase corresponding to maximal theta power. However, in contrast with this “default state,” TPSM-phase locked neurons displayed a real diversity of preferred firing phases during awake behavior, a prerequisite for TPSM to serve as a substrate for information coding.