Medial septal modulation of the ascending brainstem hippocampal synchronizing pathways in the anesthetized rat

Independent and combined electrical stimulation pairings of the medial septum (MS), posterior hypothalamus (PH), and reticular pontine oralis (RPO) of the brainstem were performed in the acute urethane anesthetized rat, while recording field activity from electrodes in either the stratum oriens or stratum moleculare of the hippocampal formation. Theta frequency and power were measured during independent stimulation of each nuclei and during combined stimulation using three pairings: (1) MS-PH (2) MS-RPO and (3) PH-RPO. Each pairing consisted of parameters known to elicit theta of a high frequency for one nucleus, and parameters known to elicit a low frequency for the second nucleus. This methodology allowed us to observe whether one nucleus preferentially modulated theta activity in the hippocampus in terms of frequency and power. The MS was observed to reset theta frequency in both the upward and downward direction when stimulated in combination with either the PH (Experiment 1) or the RPO (Experiment 2). In Experiment 3 (PH-RPO), the structure receiving the higher intensity stimulation had the predominate effect on theta frequency. With MS stimulation combinations, the power of the elicited theta activity was found to increase over the independent stimulation in some cases during Experiment 1. Likewise, in Experiment 2, the combined stimulation produced a power that in most cases was significantly greater than that measured during the independent stimulations. This effect was not observed with PH and RPO stimulation combinations. The combined stimulation of the PH and RPO yielded a power similar to the independent PH stimulations. The findings support the following conclusions: (1) the major theta generating activity of the ascending brainstem synchronizing pathways involves projections from the RPO to the PH, relayed through the MS, to the hippocampal formation; and (2) that the MS directly controls theta amplitude and secondarily translates the level of ascending brainstem activity into the appropriate frequency of hippocampal theta.