Frequency modulation of hippocampal theta by the supramammillary nucleus, and other hypothalamo-hippocampal interactions: mechanisms and functional implications.

In this paper it is argued that theta-range hippocampal EEG activity, and in particular the specific frequency at which it occurs, is critical to hippocampal function. Results of the reviewed studies suggest that in particular circumstances (in the urethane anaesthetized animal and possibly during particular behavioral states), the frequency of hippocampal theta is primarily determined in the supramammillary nucleus (SuM). Rhythmic theta-frequency neuronal activity in the SuM is relayed to, and determines the frequency of theta activity in, the septum (and hence the hippocampus). It is also suggested that in general (e.g., freely moving, as opposed to anaesthetized animals, and in all but some specific behavioral states), other ascending pathways and mechanisms in addition to those from SuM are probably also involved in the modulation of theta frequency. The posterior hypothalamic nucleus (PH) probably acts in synergy with the SuM, but it is principally involved in the release and amplitude modulation of theta. Although descending input from the septo-hippocampal system to PH and SuM is not required for theta-related neuronal activity in these structures, we provide evidence for descending, rate-limiting influences from the septo-hippocampal system to both PH and SuM during theta. These descending systems are likely involved in the suppression of theta during non-theta (i.e., sharp-wave) hippocampal EEG. In contrast to the SuM and PH, theta-related neuronal activity in the medial mammillary nucleus (MM) is dependent on theta-frequency activity in, and descending from, the septo-hippocampal system. The MM it is argued, is involved in relaying theta-frequency activity around the limbic circuitry. A role for this re-entrant process is suggested.