A fraction of neurons was significantly modulated by both PFC 4 Hz and hippocampal theta oscillations (Figure 7B; PFC: 13.7%; CA1: 21.0%; VTA: 16.9%; p < 0.05; Rayleigh test). Plotting all significantly selleck chemicals jointly modulated neurons showed that the population of phase-locked units occupied a diagonal

(Figure 7C), similar to the joint phase distribution of 4 Hz and theta oscillations (Figure 7A, second panel). The diagonal distribution of the comodulation values is an indication of the interdependent nature of neuronal phase locking to both rhythms. Comparison between jointly modulated predicting and nonpredicting PFC pyramidal neurons revealed that predicting neurons were significantly more strongly comodulated by these rhythms than nonpredicting cells (Figure 7D; p < 0.05; Figure S6). In addition, we found that local gamma oscillations in PFC and hippocampus were modulated by both PFC 4 Hz and CA1 theta oscillations (Figure S7). These findings suggest that PFC neurons, which are active in the working memory part of the task, are temporally coordinated (Jones and Wilson, 2005, Benchenane et al., 2010 and Rutishauser et al., 2010) by 4 Hz and theta oscillations.

The expected results of such coordination are that the synchronously discharging predicting cells can exert a stronger impact on downstream targets that guide behavior, as compared to the less synchronous nonpredicting population. LBH589 in vitro Finally, we compared LFP activity PD184352 (CI-1040) in PFC and hippocampus during task behaviors and in the home cage during

waking immobility, rapid eye movement (REM) sleep, and slow-wave sleep (Figure S8). PFC 4 Hz power was high during nose poking and running in the central arm and wheel, i.e., during times when working memory was active. PFC 4 Hz power was low during immobility and sleep, including theta-dominated REM sleep. Hippocampal theta power was high during running behavior and REM sleep but low during nose poking, immobility, and slow-wave sleep (Figure S8). Slow-wave sleep in both PFC and hippocampus was dominated by a large 2 Hz peak, a reflection of slow oscillation of non-REM sleep (Steriade et al., 1993). This behavior-dependent dissociation of power changes demonstrates that theta and 4 Hz oscillations are distinct rhythms with characteristically different behavioral correlates and presumably different mechanisms. Our findings demonstrate a triple time control of neurons in the PFC-VTA-hippocampus axis (Figure 8). The 4 Hz rhythm is the dominant pattern in PFC-VTA circuits, effectively modulating both local gamma oscillations and neuronal firing, whereas synchrony of neuronal spikes in the hippocampus is largely under the control of theta oscillations. Through phase coupling, 4 Hz and theta oscillations jointly coordinate gamma oscillations and neuronal assembly patterns in a task-relevant manner.