Although it is well known that high-frequency stimulation (HFS) of the subthalamic nucleus (STN) alleviates the cardinal symptoms of Parkinson's disease, the underlying mechanisms are not fully understood. We investigated the effect of stimulation from low to high frequencies on rat STN neurons in naive and dopamine-depleted slices using whole-cell, current-clamp techniques and on-line artifact suppression. Stimulation at 10 Hz evoked 10 Hz single spikes but did not significantly modify ongoing STN activity. In contrast, at therapeutically relevant frequencies (80-185 Hz), stimulation had a dual effect: it fully suppressed STN spontaneous activity and generated a robust pattern of recurrent bursts of spikes, with each spike being time-locked to a stimulus pulse. Neither the suppression of spontaneous activity nor the generation of spikes was prevented by the antagonists of the metabotropic and ionotropic receptors of glutamate and γ-aminobutyric acid. Tetrodotoxin, the Na+channel blocker, suppressed all HFS-evoked spikes, whereas nifedipin, an L-type Ca2+-channel blocker, abolished the membrane oscillations underlying bursts. Therefore, we conclude that HFS drives the STN neuronal activity by directly activating the neuronal membrane. We suggest that this pattern may remove the deleterious activity of the basal ganglia network in the parkinsonian state and drive target neurons to a high-frequency state of activity, dependent on the characteristics of STN efferent synapses and resonant properties of target membranes.
We present a detailed experimental and theoretical study of the optical response of suspensions of ferromagnetic nanoparticles (“ferroparticles”) in nematic liquid crystals (“ferronematics”), concentrating on the magnetic field-induced Frederiks transition. Even extremely low ferroparticle concentrations (at a volume fraction between 2 × 10−5 and 2 × 10−4), induce a significant additional ferronematic linear response at low magnetic field (<100 G) and a decrease in the effective magnetic Frederiks threshold. The experimental results demonstrate that our system has weak ferronematic behavior. The proposed theory takes into account the nematic diamagnetism and assumes that the effective magnetic susceptibility, induced by the nanoparticles, no longer dominates the response. The theory is in good agreement with the experimental data for the lowest concentration suspensions and predicts the main features of the more concentrated ones. The deviations observed in these cases hint at extra effects due to particle aggregation, which we have also observed directly in photographs.
Several models of partial differential equations describing the dynamics of lasers with transverse effects are introduced by using the center manifold theorem for the elimination of irrelevant variables. By taking advantage of the different time scales associated with the relaxations of the variables, we first eliminate the polarization and later the population inversion. We show that in contrast with the plane-wave models, the use of center manifold techniques is necessary to properly describe the spatiotemporal behaviors of lasers. In particular, we characterize unsuspected Hopf bifurcations for the model obtained from the adiabatic elimination of the polarization and discuss the presence of diffusive terms induced by the interaction of radiation and matter after the elimination of the population inversion. A complex Ginzburg-Landau equation is also obtained in the small-field limit.
In clinical conditions, high-frequency stimulation (HFS) of subthalamic (STN) neurons in Parkinson's disease is empirically applied at ≥100 Hz (130–185 Hz), with pulses of short duration (60–100 μs) and 1- to 3-mA amplitude. Other parameter values produce no effect or aggravate the symptoms. To gain a better understanding of the mechanisms that underlie the therapeutic action of HFS, we have compared the effects of different combinations of parameter values delivered by clinical stimulators on the activity of STN neurons recorded in whole cell patch-clamp configuration in slices. We showed that none of tested combinations of parameters silenced the neurons. Non-therapeutic combinations i.e., low-frequency pulses (10–50 Hz), even at large amplitude or width, further excited the STN neurons with respect to their spontaneous activity. In contrast, combinations in the therapeutic range (80–185 Hz, 90–200 μs, 500–800 μA) replaced the preexisting activity by spikes, time-locked to the stimuli and thus presenting a striking regularity. When increasing pulse width or amplitude in this high-frequency range, the dual effect was still present but the activity generated became more irregular. We propose that during HFS at clinically relevant parameters, STN neurons behave as stable oscillators entirely driven by the stimulation, giving an average stable STN output that overrides spontaneous activity and introduces high-frequency regular spiking in the basal ganglia network.