Iron metabolism in patients with rheumatoid arthritis.

OBJECTIVE: Anemia is the hematological issue that occurs most often as a manifestation in RA. The aim of the study was to assess iron deficiency in RA patients. PATIENTS AND METHODS: The study was carried out on 62 RA patients treated between 2016 and 2017. RESULTS: A higher percentage of RA patients compared to the control group had TSAT below 20% (43% vs. 5%), ferritin below the reference range (15% vs. 7%), sTfR above 1.59 mg/l (26% vs. 0%) and hepcidin below 14.5 ng/ml (56% vs. 2%). 60% of RA patients had iron deficiency, and 18% - anemia. Correlations were found between reduced levels of ferritin and patients being younger, female, with lower GGT and higher platelet counts. Correlations were also found between iron deficiency and patients being younger, female, having reduced hemoglobin, increased platelet counts, increased GFR, reduced GGT, lower disease activity, and less frequent use of sulfasalazine. CONCLUSIONS: Iron deficiency is common (64%) in RA patients where there is high disease activity. RA patients had lower transferrin, lower ferritin, lower hepcidin, and higher sTfR. Decreased DAS-28 and reduced hemoglobin were the strongest determinants of iron deficiency.

Long-term effects of direct current are reproduced by intermittent depolarization of myelinated nerve fibers.

Direct current (DC) potently increases the excitability of myelinated afferent fibers in the dorsal columns, both during DC polarization of these fibers and during a considerable (>1 h) postpolarization period. The aim of the present study was to investigate whether similarly long-lasting changes in the excitability of myelinated nerve fibers in the dorsal columns may be evoked by field potentials following stimulation of peripheral afferents and by subthreshold epidurally applied current pulses. The experiments were performed in deeply anesthetized rats. The effects were monitored by changes in nerve volleys evoked in epidurally stimulated hindlimb afferents and in the synaptic actions of these afferents. Both were found to be facilitated during as well as following stimulation of a skin nerve and during as well as following epidurally applied current pulses of 5- to 10-ms duration. The facilitation occurring ≤2 min after skin nerve stimulation could be linked to both primary afferent depolarization and large dorsal horn field potentials, whereas the subsequent changes (up to 1 h) were attributable to effects of the field potentials. The findings lead to the conclusion that the modulation of spinal activity evoked by DC does not require long-lasting polarization and that relatively short current pulses and intrinsic field potentials may contribute to plasticity in spinal activity. These results suggest the possibility of enhancing the effects of epidural stimulation in human subjects by combining it with polarizing current pulses and peripheral afferent stimulation and not only with continuous DC. NEW & NOTEWORTHY The aim of this study was to define conditions under which a long-term increase is evoked in the excitability of myelinated nerve fibers. The results demonstrate that a potent and long-lasting increase in the excitability of afferent fibers traversing the dorsal columns may be induced by synaptically evoked intrinsic field as well as by epidurally applied intermittent current pulses. They thus provide a new means for the facilitation of the effects of epidural stimulation.

Analysis of surface deformation in thin-film coatings by carrier frequency interferometry.

We demonstrate a method based on carrier frequency interferometry (CFI) that measures surface deformation with high accuracy. The method is applied to assess the deformation of thin-film dielectrics deposited on thick substrates. CFI measured the wavefront radius of curvature R with an accuracy of 0.2% for an R smaller than 500 m and 2% for an R between 500 and 2000 m (flat reference substrate). We show the method has a significantly larger dynamic range and sensitivity than Twyman-Green and comparable sensitivity to white light interferometry.

Elevated troponin I level assessed by a new high-sensitive assay and the risk of poor outcomes in patients with acute heart failure.

BACKGROUND: The interpretation and clinical usefulness of elevated levels of cardiac troponins in acute heart failure (AHF) remain controversial. We aimed to characterize the relationship between changes in cardiac troponin I (measured using a new high-sensitive immunoassay by single-molecule counting technology, Singulex, Alameda, USA; hs-TnI) during first 48h of hospital stay and patients' characteristics and the outcomes. METHODS AND RESULTS: We measured hs-TnI at baseline, after 24 and 48h in 130 AHF patients (mean age: 65±13years, 77% men). The percentage of patients with elevated hs-TnI (i.e., above the upper reference limit [URL]>10.19pg/mL) were: on admission - 59%, after 24h - 61%, and after 48h - 58%. Elevated baseline level of hs-TnI was associated with more severe dyspnoea on admission but neither peak level nor changes in hs-TnI during first 48h were related to the dyspnoea severity or magnitude of dyspnoea relief. During 1-year follow-up there were 32 (25%) cardiovascular deaths. Neither absolute baseline nor peak values of hs-TnI predicted cardiovascular mortality. Only changes in hs-TnI were independently associated with cardiovascular mortality with the strongest relationship seen in peak change in hs-TnI: patients with an increase vs. remaining patients - hazard ratio (95% confidence interval): 3.22 (1.52-6.82)p=0.002. CONCLUSIONS: Using the new assay (proved to be more sensitive that the other available troponin assays) we observed that approximately 60% of patients with AHF presented elevated hs-TnI above URL during first 48h of hospital stay. Only significant increase in hs-TnI predicted cardiovascular mortality.

Thin film absorption characterization by focus error thermal lensing.

A simple, highly sensitive technique for measuring absorbed power in thin film dielectrics based on thermal lensing is demonstrated. Absorption of an amplitude modulated or pulsed incident pump beam by a thin film acts as a heat source that induces thermal lensing in the substrate. A second continuous wave collimated probe beam defocuses after passing through the sample. Determination of absorption is achieved by quantifying the change of the probe beam profile at the focal plane using a four-quadrant detector and cylindrical lenses to generate a focus error signal. This signal is inherently insensitive to deflection, which removes noise contribution from point beam stability. A linear dependence of the focus error signal on the absorbed power is shown for a dynamic range of over 105. This technique was used to measure absorption loss in dielectric thin films deposited on fused silica substrates. In pulsed configuration, a single shot sensitivity of about 20 ppm is demonstrated, providing a unique technique for the characterization of moving targets as found in thin film growth instrumentation.

Does trans-spinal and local DC polarization affect presynaptic inhibition and post-activation depression?

KEY POINTS: Trans-spinal polarization was recently introduced as a means to improve deficient spinal functions. However, only a few attempts have been made to examine the mechanisms underlying DC actions. We have now examined the effects of DC on two spinal modulatory systems, presynaptic inhibition and post-activation depression, considering whether they might weaken exaggerated spinal reflexes and enhance excessively weakened ones. Direct current effects were evoked by using local intraspinal DC application (0.3-0.4 µA) in deeply anaesthetized rats and were compared with the effects of trans-spinal polarization (0.8-1.0 mA). Effects of local intraspinal DC were found to be polarity dependent, as locally applied cathodal polarization enhanced presynaptic inhibition and post-activation depression, whereas anodal polarization weakened them. In contrast, both cathodal and anodal trans-spinal polarization facilitated them. The results suggest some common DC-sensitive mechanisms of presynaptic inhibition and post-activation depression, because both were facilitated or depressed by DC in parallel. ABSTRACT: Direct current (DC) polarization has been demonstrated to alleviate the effects of various deficits in the operation of the central nervous system. However, the effects of trans-spinal DC stimulation (tsDCS) have been investigated less extensively than the effects of transcranial DC stimulation, and their cellular mechanisms have not been elucidated. The main objectives of this study were, therefore, to extend our previous analysis of DC effects on the excitability of primary afferents and synaptic transmission by examining the effects of DC on two spinal modulatory feedback systems, presynaptic inhibition and post-activation depression, in an anaesthetized rat preparation. Other objectives were to compare the effects of locally and trans-spinally applied DC (locDC and tsDCS). Local polarization at the sites of terminal branching of afferent fibres was found to induce polarity-dependent actions on presynaptic inhibition and post-activation depression, as cathodal locDC enhanced them and anodal locDC depressed them. In contrast, tsDCS modulated presynaptic inhibition and post-activation depression in a polarity-independent fashion because both cathodal and anodal tsDCS facilitated them. The results show that the local presynaptic actions of DC might counteract both excessively strong and excessively weak monosynaptic actions of group Ia and cutaneous afferents. However, they indicate that trans-spinally applied DC might counteract the exaggerated spinal reflexes but have an adverse effect on pathologically weakened spinal activity by additional presynaptic weakening. The results are also relevant for the analysis of the basic properties of presynaptic inhibition and post-activation depression because they indicate that some common DC-sensitive mechanisms contribute to them.

On the distribution of information from muscle spindles in the spinal cord; how much does it depend on random factors?

Information forwarded by individual muscle spindles is modulated by the dynamic and static gamma motoneurons in a differentiated way, depending on the coupling between the fusimotor neurons and the various intrafusal muscle fibres. Further modulation of this information at the level of spinal neurons is also differentiated because connections between individual muscle spindles and their spinal target cells are quite variable. This review illustrates this variability with respect to the spinal trajectory of muscle spindle primary afferents and the distribution of their synaptic contacts on motoneurons and other spinal neurons. It also discusses some of the consequences of this variability for the processing of information from proprioceptors.

Increased gene expression of catecholamine-synthesizing enzymes in adrenal glands contributes to high circulating catecholamines in pigs with tachycardia-induced cardiomyopathy.

High levels of circulating catecholamines have been established as fundamental pathophysiological elements of heart failure (HF). However, it is unclear whether the increased gene expression of catecholamine-synthesis enzymes in the adrenal glands contributes to these hormone abnormalities in large animal HF models. We analyzed the mRNA levels of catecholamine-synthesizing enzymes: tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AAAD), dopamine-ß-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) in adrenal glands of 18 pigs with chronic systolic non-ischaemic HF (tachycardia-induced cardiomyopathy due to right ventricle pacing) and 6 sham-operated controls. Pigs with severe HF demonstrated an increased expression of TH and DBH (but neither AAAD nor PNMT) as compared to animals with milder HF and controls (P<0.05 in all cases). The increased adrenal mRNA expression of TH and DBH was accompanied by a reduced left ventricle ejection fraction (LVEF) (P<0.001) and an elevated plasma B-type natriuretic peptide (BNP) (P<0.01), the other indices reflecting HF severity. There was a positive relationship between the increased adrenal mRNA expression of TH and DBH, and the high levels of circulating adrenaline and noradrenaline (all P<0.05). The association with noradrenaline remained significant also when adjusted for LVEF and plasma BNP, suggesting a significant contribution of adrenals to the circulating pool of catecholamines in subjects with systolic HF.

Presynaptic and postsynaptic effects of local cathodal DC polarization within the spinal cord in anaesthetized animal preparations.

KEY POINTS: Trans-spinal DC stimulation affects both postsynaptic neurons and the presynaptic axons providing input to these neurons. In the present study, we show that intraspinally applied cathodal current replicates the effects of trans-spinal direct current stimulation in deeply anaesthetized animals and affects spinal neurons both during the actual current application and during a post-polarization period. Presynaptic effects of local cathodal polarization were expressed in an increase in the excitability of skin afferents (in the dorsal horn) and group Ia afferents (in motor nuclei), both during and at least 30 min after DC application. However, although the postsynaptic facilitation (i.e. more effective) activation of motoneurons by stimuli applied in a motor nucleus was very potent during local DC application, it was only negligible once DC was discontinued. The results suggest that the prolonged effects of cathodal polarization are primarily associated with changes in synaptic transmission. ABSTRACT: The present study aimed to compare presynaptic and postsynaptic actions of direct current polarization in the spinal cord, focusing on DC effects on primary afferents and motoneurons. To reduce the directly affected spinal cord region, a weak polarizing direct current (0.1-0.3 µA) was applied locally in deeply anaesthetized cats and rats; within the hindlimb motor nuclei in the caudal lumbar segments, or in the dorsal horn within the terminal projection area of low threshold skin afferents. Changes in the excitability of primary afferents activated by intraspinal stimuli (20-50 µA) were estimated using increases or decreases in compound action potentials recorded from the dorsal roots or peripheral nerves as their measure. Changes in the postsynaptic actions of the afferents were assessed from intracellularly recorded monosynaptic EPSPs in hindlimb motoneurons and monosynaptic extracellular field potentials (evoked by group Ia afferents in motor nuclei, or by low threshold cutaneous afferents in the dorsal horn). The excitability of motoneurons activated by intraspinal stimuli was assessed using intracellular records or motoneuronal discharges recorded from a ventral root or a muscle nerve. Cathodal polarization was found to affect motoneurons and afferents providing input to them to a different extent. The excitability of both was markedly increased during DC application, although post-polarization facilitation was found to involve presynaptic afferents and some of their postsynaptic actions, but only negligibly motoneurons themselves. Taken together, these results indicate that long-lasting post-polarization facilitation of spinal activity induced by locally applied cathodal current primarily reflects the facilitation of synaptic transmission.

Presynaptic actions of transcranial and local direct current stimulation in the red nucleus.

The main aim of the present study was to examine to what extent long-lasting subcortical actions of transcranial direct current stimulation (tDCS) may be related to its presynaptic actions. This was investigated in the red nucleus, where tDCS was recently demonstrated to facilitate transmission between interpositorubral and rubrospinal neurons. Changes in the excitability of preterminal axonal branches of interpositorubral neurons close to rubrospinal neurons were investigated during and after tDCS (0.2 mA) applied over the sensorimotor cortical area in deeply anaesthetized rats and cats. As a measure of the excitability, we used the probability of antidromic activation of individual interpositorubral neurons by electrical stimuli applied in the red nucleus. Our second aim was to compare effects of weak (≤1 µA) direct current applied within the red nucleus with effects of tDCS to allow the use of local depolarization in a further analysis of mechanisms of tDCS instead of widespread and more difficult to control depolarization evoked by distant electrodes. Local cathodal polarization was found to replicate all effects of cathodal tDCS hitherto demonstrated in the rat, including long-lasting facilitation of trans-synaptically evoked descending volleys and trisynaptically evoked EMG responses in neck muscles. It also replicated all effects of anodal tDCS in the cat. In both species, it increased the excitability of preterminal axonal branches of interpositorubral neurons up to 1 h post-tDCS. Local anodal polarization evoked opposite effects. We thus show that presynaptic actions of polarizing direct current may contribute to both immediate and prolonged effects of tDCS.

Matrix metalloproteinase 9/neutrophil gelatinase associated lipocalin/tissue inhibitor of metalloproteinasess type 1 complexes are localized within cardiomyocytes and serve as a reservoir of active metalloproteinase in porcine female myocardium.

Matrix metalloproteinase 9 (MMP-9) is crucial for physiological tissue repair and pathophysiological myocardial remodeling. The regulation of its functioning has been shown to be mediated by formation of complexes with tissue inhibitor of metalloproteinases 1 (TIMP-1) and neutrophil gelatinase associated lipocalin (NGAL). We investigated the mRNA and protein expression of MMP-9, TIMP-1 and NGAL, the formation of complexes, their gelatinolytic activity and cellular localization in left ventricle (LV) from 10 female pigs with induced systolic heart failure (HF), 5 control pigs, and a woman with severe HF. The MMP-9, TIMP-1 and NGAL mRNA in LV did not differ between diseased and healthy pigs. In all pigs MMP-9, TIMP-1 and NGAL proteins were present in LV as high molecular weight (HMW) complexes (115, 130, 170 and 220 kDa), and no monomers were found. A 80 and 115 kDa gelatinolytically active bands were present in all LV homogenates. A 130-kDa active band was seen only in LV from pigs with severe HF. Similar results were found in the explanted heart of a female patient with severe HF. The incubation of the homogenates of porcine LV at 37°C resulted in appearance of 88 kDa active band, which was accompanied by a decreased intensity of HMW bands. The incubation of the homogenates of porcine LV (depleted of active MMP-9) with trypsin generated 80 and 115 kDa active bands. Immunohistochemistry revealed the presence of MMP-9 in the cytoplasm of porcine cardiomyocytes, but not in cardiofibroblasts. Our data suggest that MMP-9 originates from cardiomyocytes, forms the gelatinolytically inactive complexes with TIMP-1 and NGAL, present in normal and failing myocardium, likely serving as a reservoir of active MMP-9. Further studies are needed to elucidate the role of these HMW complexes in the extracellular matrix remodeling during the progression of HF, which presence should be considered when developing efficient strategies inhibiting myocardial matrix metalloproteinases.

Effect of short-term rapid ventricular pacing followed by pacing interruption on arterial blood pressure in healthy pigs and pigs with tachycardiomyopathy.

Ventricular tachycardia may lead to haemodynamic deterioration and, in the case of long term persistence, is associated with the development of tachycardiomyopathy. The effect of ventricular tachycardia on haemodynamics in individuals with tachycardiomyopathy, but being in sinus rhythm has not been studied. Rapid ventricular pacing is a model of ventricular tachycardia. The aim of this study was to determine the effect of rapid ventricular pacing on blood pressure in healthy animals and those with tachycardiomyopathy. A total of 66 animals were studied: 32 in the control group and 34 in the study group. The results of two groups of examinations were compared: the first performed in healthy animals (133 examinations) and the second performed in animals paced for at least one month (77 examinations). Blood pressure measurements were taken during chronic pacing--20 min after onset of general anaesthesia, in baseline conditions (20 min after pacing cessation or 20 min after onset of general anaesthesia in healthy animals) and immediately after short-term rapid pacing. In baseline conditions significantly higher systolic and diastolic blood pressure was found in healthy animals than in those with tachycardiomyopathy. During an event of rapid ventricular pacing, a significant decrease in systolic and diastolic blood pressure was found in both groups of animals. In the group of chronically paced animals the blood pressure was lower just after restarting ventricular pacing than during chronic pacing. Cardiovascular adaptation to ventricular tachycardia develops with the length of its duration. Relapse of ventricular tachycardia leads to a blood pressure decrease more pronounced than during chronic ventricular pacing.

Surface profilometry with binary axicon-vortex and lens-vortex optical elements.

We report on the interesting effect observed with the diffractive binary element, which matches the property of an axicon and vortex lens. Binary phase coding simplifies the manufacturing process and gives additional advantages for metrology purposes. Under laser beam illumination, our element produces two waves: converging and diverging. Both waves carry a single optical vortex. We show that this special diffractive element can be used to set up a simple surface profilometer.

Plasma adiponectin in heart failure with and without cachexia: catabolic signal linking catabolism, symptomatic status, and prognosis.

BACKGROUND AND AIMS: Adiponectin (ADPN) as an adipose tissue hormone contributes to regulation of energy metabolism and body composition and is associated with cardiovascular risk profile parameters. Cardiac cachexia may develop as a result of severe catabolic derangement in chronic heart failure (CHF). We aimed to determinate an abnormal ADPN regulation as a link between catabolic signalling, symptomatic deterioration and poor prognosis. METHODS AND RESULTS: We measured plasma ADPN in 111 CHF patients (age 65 ± 11, 90% male, left ventricular ejection fraction (LVEF) 36 ± 11%, peak oxygen consumption (peakVO2) 18.1 ± 5.7 l/kg*min, body mass index (BMI) 27 ± 4 kg/m(2), all mean ± standard deviation) and 36 healthy controls of similar age and BMI. Body composition was assessed by dual energy X-ray absorptiometry, insulin sensitivity was evaluated by homoeostasis model assessment, exercise capacity by spiroergometry. Plasma ADPN did not differ between CHF vs. controls (13.5 ± 11.0 vs. 10.5 ± 5.3 mg/l, p > 0.4), but increased stepwise with NYHA functional class (I/II/III: 5.7 ± 1.4/10.7 ± 8.3/19.2 ± 14.0 mg/l, ANOVA p < 0.01). Furthermore, ADPN correlated with VO2 at anaerobic threshold (r = -0.34, p < 0.05). ADPN was highest in cachectic patients (cCHF, 16%) vs. non-cachectic (ncCHF) (18.7 ± 15.0 vs. 12.5 ± 9.9 mg/l; p < 0.05). ADPN indicated mortality risk independently of established prognosticators (HR: 1.04 95% CI: 1.02-1.07; p < 0.0001). ADPN above the mean (13.5 mg/l) was associated with a 3.4 times higher mortality risk in CHF vs. patients with ADPN levels below the mean. CONCLUSION: Circulating ADPN is abnormally regulated in CHF. ADPN may be involved in impaired metabolic signalling linking disease progression, tissue wasting, and poor outcome in CHF.

Subcortical effects of transcranial direct current stimulation in the rat.

Transcranial direct current stimulation (tDCS) affects neurons at both cortical and subcortical levels. The subcortical effects involve several descending motor systems but appeared to be relatively weak, as only small increases in the amplitude of subcortically initiated descending volleys and a minute shortening of latencies of these volleys were found. The aim of the present study was therefore to evaluate the consequences of facilitation of these volleys on the ensuing muscle activation. The experiments were carried out on deeply anaesthetized rats without neuromuscular blockade. Effects of tDCS were tested on EMG potentials recorded from neck muscles evoked by weak (20-60 µA) single, double or triple stimuli applied in the medial longitudinal fascicle (MLF) or in the red nucleus (RN). Short latencies of these potentials were compatible with monosynaptic or disynaptic actions of reticulospinal and disynaptic or trisynaptic actions of rubrospinal neurons on neck motoneurons. Despite only weak effects on indirect descending volleys, the EMG responses from both the MLF and the RN were potently facilitated by cathodal tDCS and depressed by anodal tDCS. Both the facilitation and the depression developed relatively rapidly (within the first minute) but both outlasted tDCS and were present for up to 1 h after tDCS. The study thus demonstrates long-lasting effects of tDCS on subcortical neurons in the rat, albeit evoked by an opposite polarity of tDCS to that found to be effective on subcortical neurons in the cat investigated in the preceding study, or for cortical neurons in the humans.

Oxygen on an Fe monolayer on W(110): From chemisorption to oxidation.

The adsorption of oxygen on a pseudomorphic iron monolayer deposited on a W(110) surface was studied experimentally and theoretically. Standard surface characterization methods, such as Auger electron spectroscopy and low energy electron diffraction, and specific nuclear methods, such as conversion electron Mössbauer spectroscopy (CEMS) and nuclear resonant scattering of synchrotron radiation, combined with theoretical calculations based on the density functional theory allowed us to determine the structure of the oxygen adsorbate and the electronic properties of iron atoms with different oxygen coordinations. The oxygen-(3 × 2) structure on the iron monolayer was recognized and was interpreted to be a state with oxygen chemisorbed on the non-reconstructed surface with modest electron transfer from iron to oxygen. A transition from chemisorbed oxygen to the onset of Fe-oxidation is revealed by distinct changes in the CEMS spectra.

A survey of spinal collateral actions of feline ventral spinocerebellar tract neurons.

The aim of this study was to identify spinal target cells of spinocerebellar neurons, in particular the ventral spinocerebellar tract (VSCT) neurons, giving off axon collaterals terminating within the lumbosacral enlargement. Axons of spinocerebellar neurons were stimulated within the cerebellum while searching for most direct synaptic actions on intracellularly recorded hindlimb motoneurons and interneurons. In motoneurons the dominating effects were inhibitory [inhibitory postsynaptic potentials (IPSPs) in 67% and excitatory postsynaptic potentials (EPSPs) in 17% of motoneurons]. Latencies of most IPSPs indicated that they were evoked disynaptically and mutual facilitation between these IPSPs and disynaptic IPSPs evoked by group Ia afferents from antagonist muscles and group Ib and II afferents from synergists indicated that they were relayed by premotor interneurons in reflex pathways from muscle afferents. Monosynaptic EPSPs from the cerebellum were accordingly found in Ia inhibitory interneurons and intermediate zone interneurons with input from group I and II afferents but only oligosynaptic EPSPs in motoneurons. Monosynaptic EPSPs following cerebellar stimulation were also found in some VSCT neurons, indicating coupling between various spinocerebellar neurons. The results are in keeping with the previously demonstrated projections of VSCT neurons to the contralateral ventral horn, showing that VSCT neurons might contribute to motor control at a spinal level. They might thus play a role in modulating spinal activity in advance of any control exerted via the cerebellar loop.

Inhibitory inputs to four types of spinocerebellar tract neurons in the cat spinal cord.

Spinocerebellar tract neurons are inhibited by various sources of input via pathways activated by descending tracts as well as peripheral afferents. Inhibition may be used to modulate transmission of excitatory information forwarded to the cerebellum. However it may also provide information on the degree of inhibition of motoneurons and on the operation of inhibitory premotor neurons. Our aim was to extend previous comparisons of morphological substrates of excitation of spinocerebellar neurons to inhibitory input. Contacts formed by inhibitory axon terminals were characterised as either GABAergic, glycinergic or both GABAergic/glycinergic by using antibodies against vesicular GABA transporter, glutamic acid decarboxylase and gephyrin. Quantitative analysis revealed the presence of much higher proportions of inhibitory contacts when compared with excitatory contacts on spinal border (SB) neurons. However similar proportions of inhibitory and excitatory contacts were associated with ventral spinocerebellar tract (VSCT) and dorsal spinocerebellar tract neurons located in Clarke's column (ccDSCT) and the dorsal horn (dhDSCT). In all of the cells, the majority of inhibitory terminals were glycinergic. The density of contacts was higher on somata and proximal versus distal dendrites of SB and VSCT neurons but more evenly distributed in ccDSCT and dhDSCT neurons. Variations in the density and distribution of inhibitory contacts found in this study may reflect differences in information on inhibitory processes forwarded by subtypes of spinocerebellar tract neurons to the cerebellum.

Do spinocerebellar neurones forward information on spinal actions of neurones in the feline red nucleus?

We recently demonstrated that feline ventral spinocerebellar tract (VSCT) neurones monitor descending commands for voluntary movements initiated by pyramidal tract (PT) neurones as well as locomotor movements relayed by reticulospinal (RS) neurones. The aim of the present study was to examine whether VSCT neurones likewise monitor descending commands from the red nucleus (RN). Extracellular records from the spinal border (SB) subpopulation of VSCT neurons revealed that a third (31%) of SB neurones may be discharged by trains of stimuli applied in the RN. Moreover, when RN stimuli failed to discharge SB neurones they facilitated activation of some of these neurones by RS and/or PT neurones, while activation of other SB neurones was depressed. We propose that the facilitation and depression of actions of RS neurones by RN neurones might serve to reflect a higher or lower excitability of motoneurones and therefore a likely higher or lower efficacy of the RS descending commands, prompting the cerebellum to adjust the activation of reticulospinal neurones. Activation of SB neurones by RN stimuli alone would also allow monitoring and adjusting the RN descending commands. Intracellular records from SB neurones revealed both monosynaptic and disynaptic EPSPs and disynaptic IPSPs evoked by RN stimuli. The disynaptic actions remained following transection of axons of reticulospinal neurones within the medullary longitudinal fascicle (MLF) and were therefore taken to be relayed primarily by spinal neurones, in contrast to EPSPs and IPSPs evoked by PT stimuli found to be relayed by reticulospinal rather than spinal neurones.

Processing information related to centrally initiated locomotor and voluntary movements by feline spinocerebellar neurones.

Feed-back information on centrally initiated movements is processed at both supraspinal and spinal levels and is forwarded by a variety of neurones. The aim of the present study was to examine how descending commands relayed by reticulospinal neurones are monitored by a population of spinocerebellar tract neurones. Our main question was whether a spinal border (SB) subpopulation of ventral spinocerebellar tract (VSCT) neurones monitor actions of reticulospinal neurones with input from the mesencephalic locomotor region (MLR) as well as from pyramidal tract (PT) neurones. In the majority of intracellularly recorded SB neurons, stimuli applied in the MLR and in the medullary pyramids evoked EPSPs in parallel with EPSPs evoked by stimulation of axons of reticulospinal neurones in the medial longitudinal fascicle (MLF). In extracellularly recorded neurones short trains of stimuli applied in the ipsilateral and contralateral pyramids potently facilitated discharges evoked from the MLF, as well as EPSPs recorded intracellularly. In both cases the facilitation involved the disynaptic but not the monosynaptic actions. These results indicate that reticulospinal neurones activating SB neurones (or more generally VSCT neurones) are co-excited by axon-collaterals of other reticulospinal neurones and by fibres stimulated within the MLR and PTs. The study leads to the conclusion that these spinocerebellar neurones monitor descending commands for centrally initiated voluntary as well as locomotor movements relayed by reticulospinal neurones. Thereby they may provide the cerebellum with feed-back information on the likely outcome of these commands and any corrections needed to avoid errors in the issuing movements.