The medial septum (MS) is an indispensable component of the subcortical network which
synchronizes the hippocampus at theta frequency during specific stages of information
processing. GABAergic neurons exhibiting highly regular firing coupled to the hippocampal
theta rhythm are thought to form the core of the MS rhythm-generating network. In
recent studies the hyperpolarization-activated, cyclic nucleotide-gated non-selective
cation (HCN) channel was shown to participate in theta synchronization of the medial
septum. Here, we tested the hypothesis that HCN channel expression correlates with
theta modulated firing behaviour of MS neurons by a combined anatomical and electrophysiological
approach. HCN-expressing neurons represented a subpopulation of GABAergic cells in
the MS partly overlapping with parvalbumin (PV)-containing neurons. Rhythmic firing
in the theta frequency range was characteristic of all HCN-expressing neurons. In
contrast, only a minority of HCN-negative cells displayed theta related activity.
All HCN cells had tight phase coupling to hippocampal theta waves. As a group, PV-expressing
HCN neurons had a marked bimodal phase distribution, whereas PV-immunonegative HCN
neurons did not show group-level phase preference despite significant individual phase
coupling. Microiontophoretic blockade of HCN channels resulted in the reduction of
discharge frequency, but theta rhythmic firing was perturbed only in a few cases.
Our data imply that HCN-expressing GABAergic neurons provide rhythmic drive in all
phases of the hippocampal theta activity. In most MS theta cells rhythm genesis is
apparently determined by interactions at the level of the network rather than by the
pacemaking property of HCN channels alone.
