GABAergic mechanisms in regulating the activity state of substantia nigra pars reticulata neurons.

Substantia nigra reticulata is the major output structure of the basal ganglia involved in somatosensory integration and organization of movement. While previous work in vitro and in anesthetized animal preparations suggests that these neurons are autoactive and points to GABA as a primary input regulating their activity, single-unit recording coupled with iontophoresis was used in awake, unrestrained rats to further clarify the role of tonic and phasic GABA input in maintenance and fluctuations of substantia nigra reticulata neuronal activity under physiologically relevant conditions. In contrast to glutamate, which was virtually ineffective at stimulating substantia nigra reticulata neurons in awake rats, all substantia nigra reticulata neurons tested were inhibited by iontophoretic GABA and strongly excited by bicuculline, a GABA-A receptor blocker. The GABA-induced inhibition had short onset and offset latencies, a fading response pattern (a rapid decrease in rate followed by its relative restoration), and was independent of basal discharge rate. The bicuculline-induced excitation was inversely related to discharge rate and current (dose)-dependent in individual units. However, the average discharge rate during bicuculline applications at different currents increased to a similar plateau ( approximately 60 impulses/s), which was about twice the mean basal rates. The excitatory effects of bicuculline were phasically inhibited or completely blocked by brief GABA applications and generally mimicked by gabazine, another selective GABA antagonist. These data as well as neuronal inhibitions induced by nipecotic acid, a selective GABA uptake inhibitor, suggest that substantia nigra reticulata neurons in awake, quietly resting conditions are under tonic, GABA-mediated inhibition. Therefore, because of inherent autoactivity and specifics of afferent inputs, substantia nigra reticulata neurons are very sensitive to phasic alterations in GABA input, which appears to be the primary factor determining fluctuations in their activity states under physiological conditions. While these cells are relatively insensitive to direct activation by glutamate, and resistant to a continuous increase in GABA input, they appear to be very sensitive to a diminished GABA input, which may release them from tonic inhibition and determine their functional hyperactivity.

Resonant bar simulations in media with localized damage.

As a rule, problems of wave propagation in finite media with non-uniform spatial distribution of material properties can only be tackled by numerical models. In addition, the modeling of damage features in a material requires the introduction of locally non-linear and--more important--non-unique equations of state. Using a multiscale approach, we have implemented a non-linear hysteretic stress-strain relation based on the Preisach-Mayergoyz (PM) model, into a numerical elastodynamic finite integration technique program, which has originally been developed for linearly elastic wave propagation in inhomogeneous media. The simulation results show qualitatively good agreement with data of non-linear resonant bar experiments in homogeneously non-linear and hysteretic media. When the PM density distribution of hysteretic units at the mesoscopic level is not uniform and/or confined to a finite area in stress-stress space, the response at high amplitude excitation tend to deviate from the quasi-analytical results obtained in the case of a uniform PM-space density. Localized microdamage features in an intact medium can be modeled by conceiving finite zones with pronounced hysteretic stress-strain relations within a "linear" surrounding. Forward calculations reveal a significant influence of the amplitude dependent resonance behavior on the location (edge versus center of a bar), the extend (width of the zone) and the degree (density of hysteretic units) of damage.

The influence of localized damage in a sample on its resonance spectrum.

A nonlinear version of resonance ultrasound spectroscopy (RUS) theory is presented. This is important for NDT-purposes as damage manifests itself more pronounced and in an earlier stage by changes in the nonlinear elastic constants. General equations are derived for the 1-D case, describing the interaction between the modes due to the presence of nonlinearity. An analytical solution of these equations is derived which predicts the shift of the resonance frequency versus amplitude in a bar with localized damage. The damage was modelled as a finite region, having a constant cubic nonlinearity, in an otherwise linear 1-D bar. The analytical expressions for the shifts in resonance frequency at different modes were used to infer information about the position, nonlinearity and width of the damage. Unlike other techniques, the proposed method does not require scanning to locate the defect, as it lets the different modes, each with a different vibration pattern, probe the structure.

Acousto-optic lens for pulsed lasers.

Theoretical predictions of the acousto-optic interaction under Raman-Nath conditions of ultrasound and laser light with a beam width w comparable to or smaller than the ultrasonic wavelength lambda are experimentally investigated, and good agreement between experiment and prediction is found. The experimental setup consists of a pulsed laser, emitting pulses that are synchronized with the sound frequency by means of a controllable delay time. When w approximately lambda, strong focusing is obtained for most delay times. The lensing properties of this configuration are carefully investigated.

The reflection of bounded inhomogeneous waves on a liquid/solid interface.

Fourier analysis and normal mode theory are used to describe the reflection of bounded inhomogeneous waves on a liquid/solid interface. Nonspecular reflection phenomena in the Rayleigh angle are studied in detail. In this way, an explanation is given for the Rayleigh dip phenomenon for positive inhomogeneity factors and the related result of a reflection coefficient larger than unity when the sign of the inhomogeneity factor is reversed. In the limit of large beamwidths, the reflection coefficient predicted by the infinite plane inhomogeneous wave theory is obtained. These results are entirely consistent with the experimental work published by Deschamps [J. Acoust. Soc. Am. 96, 2841-2848 (1994)]. The energy efficiency of Rayleigh wave excitation is investigated as well. It is shown that for large beamwidths, the energy efficiency for bounded inhomogeneous waves is considerably higher in comparison with Gaussian and square-profiled beams.

Thin coating characterization by Rayleigh waves: an analytical model based on normal-mode theory.

The acousto-optic technique to evaluate coated substrates, presented by Devolder et al. [Appl. Phys. Lett. 68, 1732 (1996)], uses the phase dependence of the reflected beam on the coating parameters. In this theoretical paper, a fully analytical model, based on normal-mode theory, is applied to this problem. It gives a transparent expression for the phase shift between the reflected and the incident field due to the presence of thin coatings (coating thickness much smaller than wavelength sound). The known numerical results from Fourier simulations, i.e. the phase dependency on the coating parameters and the advantages of using higher frequencies and wider beams, are reproduced. However, thanks to the analytical nature of the new theory, additional results are obtained. The calculation time is reduced by two orders of magnitude, which is important for the inverse problem. A technique for absolute thickness measurements is proposed. Measuring more to the right of the second reflected maximum increases the phase sensitivity. The versatility of the normal-mode approach is illustrated by applying it to other nondestructive testing (NDT) applications, such as hardness determination and adhesion testing, which are briefly discussed.

High frequency stimulation of the subthalamic nucleus increases the extracellular contents of striatal dopamine in normal and partially dopaminergic denervated rats.

The subthalamic nucleus (STN) has come under focus in Parkinson disease (PD) because of recent advances in the understanding of the functional organization of the basal ganglia in normal and pathological conditions. Manipulations of the STN have been described to compensate for some imbalance in motor output of the basal ganglia in animal models of PD and have been proposed as a potential therapeutic target in humans. Indeed, high frequency stimulation (HFS) (130 Hz) of the STN has beneficial effects in severe parkinsonian patients but the precise mechanisms underlying these clinical results remain to be elucidated. To date, very little is known concerning the effect of HFS-STN on striatal dopaminergic transmission. Since it has been reported that dopaminergic medication may be reduced in PD patients under HFS-STN, our goal was to study the effect of HFS-STN on striatal dopamine (DA) transmission by using intracerebral microdialysis in normal and partially DA denervated rats. Our results show that HFS STN induces a significant increase of extracellular DA in the striatum of normal and partially DA lesioned rats while striatal extracellular levels of DOPAC were not affected. We conclude that HFS-STN acts directly and/or indirectly on striatal DA levels in control or partially DA lesioned rats.

Effects of high frequency stimulation of subthalamic nucleus on extracellular glutamate and GABA in substantia nigra and globus pallidus in the normal rat.

High frequency stimulation (130 Hz) of the subthalamic nucleus has dramatic beneficial motor effects in severe parkinsonian patients. However, the mechanisms underlying these clinical results remain obscure. The objective of the present work was to study the neurochemical changes induced in rats by high frequency stimulation of the subthalamic nucleus by using intracerebral microdialysis within its target structures. Our results show that high frequency stimulation of the subthalamic nucleus induces a significant increase of extracellular glutamate levels in the ipsilateral globus pallidus and substantia nigra while GABA was augmented only in the substantia nigra. These data suggest that functional effects induced by high frequency stimulation of the subthalamic nucleus might imply distal mechanisms involving the synaptic relationships with the subthalamic efferences. They question the current view that the direct inhibition of the subthalamic neurons is induced by high frequency stimulation.

Unrelated course of subthalamic nucleus and globus pallidus neuronal activities across vigilance states in the rat.

The pallido-subthalamic pathway powerfully controls the output of the basal ganglia circuitry and has been implicated in movement disorders observed in Parkinson's disease (PD). To investigate the normal functioning of this pathway across the sleep-wake cycle, single-unit activities of subthalamic nucleus (STN) and globus pallidus (GP) neurons were examined, together with cortical electroencephalogram and nuchal muscular activity, in non-anaesthetized head-restrained rats. STN neurons shifted from a random discharge in wakefulness (W) to a bursting pattern in slow wave sleep (SWS), without any change in their mean firing rate. This burst discharge occurred in the 1-2 Hz range, but was not correlated with cortical slow wave activity. In contrast, GP neurons, with a mean firing rate higher in W than in SWS, exhibited a relatively regular discharge whatever the state of vigilance. During paradoxical sleep, both STN and GP neurons increased markedly their mean firing rate relative to W and SWS. Our results are not in agreement with the classical 'direct/indirect' model of the basal ganglia organization, as an inverse relationship between STN and GP activities is not observed under normal physiological conditions. Actually, because the STN discharge pattern appears dependent on coincident cortical activity, this nucleus can hardly be viewed as a relay along the indirect pathway, but might rather be considered as an input stage conveying corticothalamic information to the basal ganglia.