Information processing in the hippocampus critically relies on its reciprocal interaction
with the medial septum (MS). Synchronization of the septo-hippocampal system was demonstrated
during both major hippocampal activity states, the regular theta rhythm and the large
amplitude irregular activity. Previous experimental and modeling data suggest that
the MS provides rhythmic drive to the hippocampus, and hippocampo-septal feedback
synchronizes septal pacemaker units. However, this view has recently been questioned
based on the possibility of intrahippocampal theta genesis. Previously, we identified
putative pacemaker neurons expressing parvalbumin (PV) and/or the pacemaker hyperpolarization-activated
and cyclic nucleotide-gated nonselective cation channel (HCN) in the MS. In this study,
by analyzing the temporal relationship of activity between the PV/HCN-containing medial
septal neurons and hippocampal local field potential, we aimed to uncover whether
the sequence of events during theta formation supports the classic view of septal
drive or the challenging theory of hippocampal pacing of theta. Importantly, by implementing
a circular statistical method, a temporal lead of these septal neurons over the hippocampus
was observed on the course of theta synchronization. Moreover, the activity of putative
hippocampal interneurons also preceded hippocampal local field theta, but by a shorter
time period compared with PV/HCN-containing septal neurons. Using the concept of mutual
information, the action potential series of PV/HCN-containing neurons shared higher
amount of information with hippocampal field oscillation than PV/HCN-immunonegative
cells. Thus, a pacemaker neuron population of the MS leads hippocampal activity, presumably
via the synchronization of hippocampal interneurons.
