  The subthalamic nucleus (STN) has an important role in the pathophysiology of
the basal ganglia in Parkinson's disease. The ability of STN cells to generate
bursting rhythms under either transient or sustained hyperpolarization may
underlie the excessively synchronous beta rhythms observed in Parkinson's
disease. In this study, we developed a conductance-based single compartment
model of an STN neuron, which is able to generate characteristic activity
patterns observed in experiments including hyperpolarization-induced bursts and
post-inhibitory rebound bursts. This study focused on the role of three
currents in rhythm generation: T-type calcium (CaT) current, L-type calcium
(CaL) current, and hyperpolarization-activated cyclic nucleotide-gated (HCN)
current. To investigate the effects of these currents in rhythm generation, we
performed a bifurcation analysis using slow variables in these currents.
Bifurcation analysis showed that the HCN current promotes single-spike activity
patterns rather than bursting in agreement with experimental results. It also
showed that the CaT current is necessary for characteristic bursting activity
patterns. In particular, the CaT current enables STN neurons to generate these
activity patterns under hyperpolarizing stimuli. The CaL current enriches and
reinforces these characteristic activity patterns. In hyperpolarization-induced
bursts or post-inhibitory rebound bursts, the CaL current allows STN neurons to
generate long bursting patterns. Thus, bifurcation analysis explained the
synergistic interaction of the CaT and CaL currents, which enables STN neurons
to respond to hyperpolarizing stimuli in a salient way. The results of this
study implicate the importance of CaT and CaL currents in the pathophysiology
of the basal ganglia in Parkinson's disease.
