Cholinergic mechanisms in spinal locomotion-potential target for rehabilitation approaches.

Previous experiments implicate cholinergic brainstem and spinal systems in the control of locomotion. Our results demonstrate that the endogenous cholinergic propriospinal system, acting via M2 and M3 muscarinic receptors, is capable of consistently producing well-coordinated locomotor activity in the in vitro neonatal preparation, placing it in a position to contribute to normal locomotion and to provide a basis for recovery of locomotor capability in the absence of descending pathways. Tests of these suggestions, however, reveal that the spinal cholinergic system plays little if any role in the induction of locomotion, because MLR-evoked locomotion in decerebrate cats is not prevented by cholinergic antagonists. Furthermore, it is not required for the development of stepping movements after spinal cord injury, because cholinergic agonists do not facilitate the appearance of locomotion after spinal cord injury, unlike the dramatic locomotion-promoting effects of clonidine, a noradrenergic α-2 agonist. Furthermore, cholinergic antagonists actually improve locomotor activity after spinal cord injury, suggesting that plastic changes in the spinal cholinergic system interfere with locomotion rather than facilitating it. Changes that have been observed in the cholinergic innervation of motoneurons after spinal cord injury do not decrease motoneuron excitability, as expected. Instead, the development of a "hyper-cholinergic" state after spinal cord injury appears to enhance motoneuron output and suppress locomotion. A cholinergic suppression of afferent input from the limb after spinal cord injury is also evident from our data, and this may contribute to the ability of cholinergic antagonists to improve locomotion. Not only is a role for the spinal cholinergic system in suppressing locomotion after SCI suggested by our results, but an obligatory contribution of a brainstem cholinergic relay to reticulospinal locomotor command systems is not confirmed by our experiments.

Wallerian degeneration after spinal cord lesions in cats detected with diffusion tensor imaging.

One goal of in vivo neuroimaging is the detection of neurodegenerative processes and anatomical reorganizations after spinal cord (SC) injury. Non-invasive examination of white matter fibers in the living SC can be conducted using magnetic resonance diffusion-weighted imaging. However, this technique is challenging at the spinal level due to the small cross-sectional size of the cord and the presence of physiological motion and susceptibility artifacts. In this study, we acquired in vivo high angular resolution diffusion imaging (HARDI) data at 3T in cats submitted to partial SC injury. Cats were imaged before, 3 and 21 days after injury. Spatial resolution was enhanced to 1.5 × 1.5 × 1 mm(3) using super-resolution technique and distortions were corrected using the reversed gradient method. Tractography-derived regions of interest were generated in the dorsal, ventral, right and left quadrants, to evaluate diffusion tensor imaging (DTI) and Q-Ball imaging metrics with regards to their sensitivity in detecting primary and secondary lesions. A three-way ANOVA tested the effect of session (intact, D3, D21), cross-sectional region (left, right, dorsal and ventral) and rostrocaudal location. Significant effect of session was found for FA (P<0.001), GFA (P<0.05) and radial diffusivity (P<0.001). Post-hoc paired T-test corrected for multiple comparisons showed significant changes at the lesion epicenter (P<0.005). More interestingly, significant changes were also found several centimeters from the lesion epicenter at both 3 and 21 days. This decrease was specific to the type of fibers, i.e., rostrally to the lesion on the dorsal aspect of the cord and caudally to the lesion ipsilaterally, suggesting the detection of Wallerian degeneration.

A semi-automated software tool to study treadmill locomotion in the rat: from experiment videos to statistical gait analysis.

A computer-aided method for the tracking of morphological markers in fluoroscopic images of a rat walking on a treadmill is presented and validated. The markers correspond to bone articulations in a hind leg and are used to define the hip, knee, ankle and metatarsophalangeal joints. The method allows a user to identify, using a computer mouse, about 20% of the marker positions in a video and interpolate their trajectories from frame-to-frame. This results in a seven-fold speed improvement in detecting markers. This also eliminates confusion problems due to legs crossing and blurred images. The video images are corrected for geometric distortions from the X-ray camera, wavelet denoised, to preserve the sharpness of minute bone structures, and contrast enhanced. From those images, the marker positions across video frames are extracted, corrected for rat "solid body" motions on the treadmill, and used to compute the positional and angular gait patterns. Robust Bootstrap estimates of those gait patterns and their prediction and confidence bands are finally generated. The gait patterns are invaluable tools to study the locomotion of healthy animals or the complex process of locomotion recovery in animals with injuries. The method could, in principle, be adapted to analyze the locomotion of other animals as long as a fluoroscopic imager and a treadmill are available.

Varieties of stable vortical solitons in Ginzburg-Landau media with radially inhomogeneous losses.

Using a combination of the variation approximation and direct simulations, we consider the model of the light transmission in nonlinearly amplified bulk media, taking into account the localization of the gain, i.e., the linear loss shaped as a parabolic function of the transverse radius, with a minimum at the center. The balance of the transverse diffraction, self-focusing, gain, and the inhomogeneous loss provides for the hitherto elusive stabilization of vortex solitons, in a large zone of the parameter space. Adjacent to it, stability domains are found for several novel kinds of localized vortices, including spinning elliptically shaped ones, eccentric elliptic vortices which feature double rotation, spinning crescents, and breathing vortices.

Short waves in ferromagnetic media.

We discuss the propagation of nonlinear electromagnetic short waves in a magnetically saturated ferromagnetic thick film. The sample is magnetized to saturation by a field perpendicular to both the film plane and the propagation direction. A (2+1) dimensional asymptotic model equation generalizing the sine-Gordon one is derived. Line soliton solutions are exhibited; their stability condition is derived. When unstable, line solitons decay into stable two-dimensional lumps, which are studied both numerically and analytically.

Passively mode-locked erbium-doped double-clad fiber laser operating at the 322nd harmonic.

We report passive mode locking of a soliton erbium-doped double-clad fiber laser operating at the 322nd harmonic of the fundamental cavity frequency. Repetition rates up to 3 GHz have been obtained with pulses of 1 ps duration and 18 pJ of energy. The supermode suppression at the 322nd harmonic is better than 25 dB. In addition, the transition dynamics from a bunched state of pulses to stable harmonic mode locking is presented, revealing a very long time scale.

Investigations on spinal cord fMRI of cats under ketamine.

Functional magnetic resonance imaging (fMRI) of the spinal cord has been the subject of intense research for the last ten years. An important motivation for this technique is its ability to detect non-invasively neuronal activity in the spinal cord related to sensorimotor functions in various conditions, such as after spinal cord lesions. Although promising results of spinal cord fMRI have arisen from previous studies, the poor reproducibility of BOLD activations and their characteristics remain a major drawback. In the present study we investigated the reproducibility of BOLD fMRI in the spinal cord of cats (N=9) by repeating the same stimulation protocol over a long period (approximately 2 h). Cats were anaesthetized with ketamine, and spinal cord activity was induced by electrical stimulation of cutaneous nerves of the hind limbs. As a result, task-related signals were detected in most cats with relatively good spatial specificity. However, BOLD response significantly varied within and between cats. This variability was notably attributed to the moderate intensity of the stimulus producing a low amplitude haemodynamic response, variation in end-tidal CO(2) during the session, low signal-to-noise ratio (SNR) in spinal fMRI time series and animal-specific vascular anatomy. Original contributions of the present study are: (i) first spinal fMRI experiment in ketamine-anaesthetized animals, (ii) extensive study of intra- and inter-subject variability of activation, (iii) characterisation of static and temporal SNR in the spinal cord and (iv) investigation on the impact of CO(2) end-tidal level on the amplitude of BOLD response.

Collisions between counter-rotating solitary vortices in the three-dimensional Ginzburg-Landau equation.

We report results of collisions between coaxial vortex solitons with topological charges +/-S in the complex cubic-quintic Ginzburg-Landau equation. With the increase of the collision momentum, merger of the vortices into one or two dipole or quadrupole clusters of fundamental solitons (for S=1 and 2, respectively) is followed by the appearance of pairs of counter-rotating "unfinished vortices," in combination with a soliton cluster or without it. Finally, the collisions become elastic. The clusters generated by the collisions are very robust, while the "unfinished vortices," eventually split into soliton pairs.

Single-oscillation two-dimensional solitons of magnetic polaritons.

The propagation of bulk polaritons in ferromagnetic slab is considered through a short-wavelength approximation. Neither the damping nor the demagnetizing field do affect essentially the propagation and stability of the line soliton. The stable line soliton may be destroyed by background instability: the latter is suppressed in a narrow strip. The unstable line soliton decays into lumps, which can be described both numerically and through a variational approach. Lump interactions are mentioned.

Characteristics and mechanisms of locomotion induced by intraspinal microstimulation and dorsal root stimulation in spinal cats.

Intraspinal microstimulation (ISMS) through a single microelectrode can induce locomotion in cats spinalized at T(13) 1 wk before (untrained) or after 3-5 wk of treadmill training. Here we study the optimal parameters of ISMS and the characteristics of locomotion evoked. ISMS was applied in the dorsal region of segments L(3)-S(1) at different lateralities (midline to 2.5 mm) and after an intravenous injection of clonidine (noradrenergic agonist). Kinematics and electromyographic recordings were used to characterize locomotion. ISMS could induce a bilateral locomotor pattern similar to that obtained with perineal stimulation, and the characteristics of locomotion varied according to the spinal segment stimulated. Mechanisms by which ISMS could evoke locomotion were then investigated by stimulating, inactivating, or lesioning different spinal structures. Dorsal root stimulation (DRS), just like ISMS, could evoke a variety of ipsi- and bilateral nonlocomotor movements as well as locomotor responses. This suggests that sensory afferent pathways are involved in the production of locomotion by ISMS. Microinjections of yohimbine (noradrenergic antagonist) in L(3) and L(4) segments or a complete second spinal lesion at L(3)-L(4) abolished all locomotor activity evoked by ISMS applied at more caudal segments. Progressive dorsoventral spinal lesions at L(3) or L(4) and restricted ventral lesions at L(4) further suggest that the integrity of the ventral or ventrolateral funiculi as well as the L(3)-L(4) segments are critical for the induction of locomotion by ISMS at L(5) to S(1) or by DRS at these caudal segments.

Quintic complex Ginzburg-Landau model for ring fiber lasers.

The dynamics of a fiber ring laser mode locked by nonlinear polarization rotation is reduced to a quintic complex Ginzburg-Landau (CGLQ) equation. The coefficients of the equation are explicitly given as functions of the physical parameters of the laser, especially the orientation of the phase plates. Then known results about analytic solutions, stability of pulse-like solutions, and bound states of the CGLQ equation are examined from the point of view of their dependence with regard to the physical parameters.

Spatiotemporal optical pulse control using microwaves.

The Davey-Stewartson system allows us to describe the interaction between a spatiotemporal optical pulse and adequately matched microwaves. We show that the interaction can lead to the formation of a two-dimensional soliton which is robust in the sense that it occurs in a wide range of parameters of the incident optical pulse and microwaves, and of the material used.

Mid-lumbar segments are needed for the expression of locomotion in chronic spinal cats.

In acute experiments performed in decerebrated and spinalized (T13) cats, an intraspinal injection of clonidine, a noradrenergic agonist, restricted to mid-lumbar segments L3-L4, can induce hindlimb locomotion, whereas yohimbine, a noradrenergic antagonist, can block spinal locomotion, and a second spinal lesion at L4 can abolish all locomotor activity. In the present study, we investigated whether the abolition of locomotion after this second spinal lesion was due to an acute spinal shock or to the functional disconnection of the rostral and caudal lumbar segments. In seven cats, first spinalized at T13 and having recovered treadmill locomotion, a second transection was performed at lower lumbar levels. Video and electromyographic recordings were used to evaluate locomotor performance. Results show that after a second transection at L2 or rostral L3 levels, spinal locomotion was maintained; when the second lesion was performed at caudal L3 or L4, all locomotor activity was abolished even after several weeks of attempted locomotor training; vigorous fast paw shakes (FPS) were observed in all cases; and after an intraperitoneal injection of clonidine in cats with a second transection below L4, perineal stimulation induced hyperextension of the hindlimbs but no locomotion. Considering that the main motoneuron pools of the hindlimbs are caudal to L4 and are still functional after the second spinal transection, as evidenced by the presence of FPS, we conclude that the mid-lumbar spinal segments are essential for the specific expression of spinal locomotion but not necessarily for other rhythmic motor patterns.

Control of the refractive index in photopolymerizable materials for (2+1)D solitary wave guide formation.

We report an experimental and theoretical study on the optimization of (2+1)D self-written waveguide formation inside a photopolymerizable material. The accurate control of the refractive index value inside the bulk of the material during the polymerization process gives us the opportunity to define a virtual core and a virtual cladding for the system. The V value which characterizes the guidance properties of a fiber can be applied to this propagation. The control of the V value allows us to propagate single mode or multimode waveguides on a few centimeters. Numerical simulations of these waveguides based on a paraxial model including both photopolymerization and Kerr effect give very good agreement with our experimental results.

Adaptive changes of locomotion after central and peripheral lesions.

This paper reviews findings on the adaptive changes of locomotion in cats after spinal cord or peripheral nerve lesions. From the results obtained after lesions of the ventral/ventrolateral pathways or the dorsal/dorsolateral pathways, we conclude that with extensive but partial spinal lesions, cats can regain voluntary quadrupedal locomotion on a treadmill. Although tract-specific deficits remain after such lesions, intact descending tracts can compensate for the lesioned tracts and access the spinal network to generate voluntary locomotion. Such neuroplasticity of locomotor control mechanisms is also demonstrated after peripheral nerve lesions in cats with intact or lesioned spinal cords. Some models have shown that recovery from such peripheral nerve lesions probably involves changes at the supra spinal and spinal levels. In the case of somesthesic denervation of the hindpaws, we demonstrated that cats with a complete spinal section need some cutaneous inputs to walk with a plantigrade locomotion, and that even in this spinal state, cats can adapt their locomotion to partial cutaneous denervation. Altogether, these results suggest that there is significant plasticity in spinal and supraspinal locomotor controls to justify the beneficial effects of early proactive and sustained locomotor training after central (Rossignol and Barbeau 1995; Barbeau et al. 1998) or peripheral lesions.

Polarization switching in a planar optical waveguide.

The multiscale expansion formalism is applied to the study of nonlinear planar optical waveguides. It allows us to describe the linear and nonlinear propagation for both transverse electric and transverse magnetic modes, and the interaction between them. An accurate computation of the nonlinear self- and cross-phase modulation coefficients allows one to give account of the polarization switching which has been observed experimentally.

Recovery of locomotion in the cat following spinal cord lesions.

In most species, locomotor function beneath the level of a spinal cord lesion can be restored even if the cord is completely transected. This suggests that there is, within the spinal cord, an autonomous network of neurons capable of generating a locomotor pattern independently of supraspinal inputs. Recent studies suggest that several physiological and neurochemical changes have to occur in the neuronal networks located caudally to the lesion to allow the expression of spinal locomotion. Some evidence of this plasticity will be addressed in this review. In addition, original data on the functional organisation of the lumbar spinal cord will also be presented. Recent works in our lab show that segmental responsiveness of the spinal cord of the cat to locally micro-injected drugs in different lumbar segments, in combination with complete lesions at various level of the spinal cord, suggest a rostro-caudal organisation of spinal locomotor control. Moreover, the integrity of midlumbar segments seems to be crucial for the expression of spinal locomotion. These data suggest that the regions of critical importance for locomotion can be confined to a restricted portion of the spinal cord. Later, these midlumbar segments could be targeted by electrical stimulation or grafts to improve recovery of function. Understanding the changes in spinal cord neurophysiology and neurochemistry after a lesion is of critical importance to the improvement of treatments for locomotor rehabilitation in spinal-cord-injured patients.

Corticospinal control of locomotor pathways generating extensor activities in the cat.

Interneuronal convergence of corticospinal and segmental pathways involved with the generation of extensor activities during locomotion was investigated in decerebrate and partially spinalized cats. L-dihydroxyphenylalanine (L-DOPA) was slowly injected until long-latency, long-lasting discharges could be evoked by the stimulation of contralateral flexor reflex afferents (coFRA) and the group I autogenetic inhibition was reversed to polysynaptic excitation in extensor motoneurons. Under these conditions, we stimulated in alternation the contralateral pyramidal tract (PT), group I afferents from knee and ankle extensor muscles, and both stimuli together. We did the same for the stimulation of PT and of coFRA. Clear polysynaptic EPSPs could be evoked from all three sources in 32 extensor motoneurons. Convergence was inferred from spatial facilitation, which occurred when the amplitude of the EPSPs evoked by the combined stimuli was notably larger than the algebraic sum of the EPSPs evoked by individual stimulation. Spatial facilitation was found between PT and extensor group I inputs in 30/59 tests (51%) in 20 motoneurons and in all cases (6/6) between PT and coFRA in six motoneurons. When fictive locomotion was induced with further injection of L-DOPA, PT descending volleys from the same stimulating site could reset the stepping rhythm by initiating bursts of activity in all extensors. These results indicate that at least some of the corticospinal fibers project onto interneurons shared by the coFRA and the polysynaptic excitatory group I pathways to extensors. The implications of such convergence patterns on the organization of the extensor "half-center" for locomotion are discussed.

Bulbospinal control of spinal cord pathways generating locomotor extensor activities in the cat.

Intracellular recording of lumbosacral motoneurones in the decerebrate and partially spinalized cat injected with nialamide and L-dihydroxyphenylalanine (l-DOPA) was used to investigate the interneuronal convergence of two bulbospinal pathways and of the segmental pathways involved with the generation of extensor activities during locomotion. Deiter's nucleus (DN) or the medial longitudinal fasciculus (MLF) was stimulated in alternation with, and in combination with, stimulation of group I afferents from extensor muscles or of contralateral flexor reflex afferents (coFRA). The evoked polysynaptic EPSPs were recorded in extensor motoneurones when long-latency, long-lasting discharges were evoked by the stimulation of coFRA and when the group I autogenetic inhibition in extensors was reversed to polysynaptic excitation. Spatial facilitation was inferred when the amplitude of the EPSPs evoked by the combined stimuli was notably larger than the algebraic sum of the EPSPs evoked by individual stimulation. Both DN (16 motoneurones) and MLF inputs (8 motoneurones) showed spatial facilitation when preceded by coFRA stimuli and both could reset the rhythm of fictive stepping by triggering a precocious extensor phase. MLF showed spatial facilitation with extensor group I inputs in 69% of trials but DN failed to show spatial facilitation in any cells. These results indicate that DN and MLF project to the coFRA pathways of the extensor half-centre for locomotion and MLF, but not DN, converge on segmental interneurones of the extensor group I pathways. The implications of such convergence patterns on the functional organization of the extensor half-centre are discussed.