Rpt5-Derived Analogs Stimulate Human Proteasome Activity in Cells and Degrade Proteins Forming Toxic Aggregates in Age-Related Diseases.

Aging and age-related diseases are associated with a decline in the capacity of protein turnover. Intrinsically disordered proteins, as well as proteins misfolded and oxidatively damaged, prone to aggregation, are preferentially digested by the ubiquitin-independent proteasome system (UIPS), a major component of which is the 20S proteasome. Therefore, boosting 20S activity constitutes a promising strategy to counteract a decrease in total proteasome activity during aging. One way to enhance the proteolytic removal of unwanted proteins appears to be the use of peptide-based activators of the 20S. In this study, we synthesized a series of peptides and peptidomimetics based on the C-terminus of the Rpt5 subunit of the 19S regulatory particle. Some of them efficiently stimulated human 20S proteasome activity. The attachment of the cell-penetrating peptide TAT allowed them to penetrate the cell membrane and stimulate proteasome activity in HEK293T cells, which was demonstrated using a cell-permeable substrate of the proteasome, TAS3. Furthermore, the best activator enhanced the degradation of aggregation-prone α-synuclein and Tau-441. The obtained compounds may therefore have the potential to compensate for the unbalanced proteostasis found in aging and age-related diseases.

Do long-lasting effects of epidural polarization of afferent fibres depend on persistent sodium current?

Few attempts have so far been made to define the mechanisms underlying the hour-long effects of trans-spinal stimulation combined with epidural polarization. In the present study, we investigated the potential involvement of non-inactivating sodium channels in afferent fibres. To this end, riluzole, a blocker of these channels, was administered locally to the dorsal columns close to the site of the excitation of afferent nerve fibres by epidural stimulation in deeply anaesthetized rats in vivo. Riluzole did not prevent the induction of the polarization-evoked sustained increase in the excitability of dorsal column fibres but tended to weaken it. It likewise weakened but did not abolish the sustained polarization-evoked shortening of the refractory period of these fibres. These results lead to the conclusion that the persistent sodium current may contribute to the sustained post-polarization-evoked effects but is only partly involved in both the induction and the expression of these effects.

Basic principles of processing of afferent information by spinal interneurons.

Integrative functions of spinal interneurons are well recognized but the relative role of different interneuronal populations in this process continues to be investigated. It therefore appeared useful to review the principles of integration of afferent information by the interneurons analyzed so far as these principles should apply also to those remaining to be analyzed. Considering the results of both functional and morphological studies of spinal interneurons and of the morphology and immunochemistry of afferent fibers that provide input to them, the following five basic principles of processing of afferent information by them will be outlined; 1) afferent information of any origin is forwarded to several neuronal populations, 2) information from any sources of input is distributed unevenly, 3) input from several sources is integrated by individual neurons as well as by their populations, 4) specific combinations of input are integrated by different neuronal populations, and 5) afferent input to spinal interneurons is only one of the features distinguishing their functional populations. As the spinal neuronal organization and properties of neurons and afferent fibers in the so far investigated species (cat, rodents, and primates) have been found to resemble, future studies using molecular techniques in the mouse should allow the new data to integrate with those of the preceding studies and the principles outlined earlier as well as any new ones should apply also in humans.

Long-term modulation of the axonal refractory period.

The main question addressed in this study was whether the refractoriness of nerve fibres can be modulated by their depolarisation and, if so, whether depolarisation of nerve fibres evokes a long-term decrease in the duration of the refractory period as well as the previously demonstrated increase in their excitability. This was investigated on nerve fibres within the dorsal columns, dorsal roots and peripheral nerves in deeply anaesthetised rats in vivo. The results revealed major differences depending on the sites of fibre stimulation and polarisation. Firstly, the relative refractory period was found to be shorter in epidurally stimulated dorsal column fibres than in fibres stimulated at other sites. Secondly, the minimal effective interstimulus intervals reflecting the absolute refractory period were likewise shorter for nerve fibres within the dorsal columns even though action potentials evoked by the second of a pair of stimuli were similarly delayed with respect to the preceding action potentials at all the stimulation sites. Thirdly, the minimal interstimulus intervals were reduced by epidurally applied cathodal direct current polarisation but not at other stimulation sites. Consequently, higher proportions of dorsal column fibres could be excited at higher frequencies, especially following their depolarisation, at interstimulus intervals as short as 0.5-0.7 ms. The results demonstrate that epidural depolarisation results in long-lasting effects not only on the excitability but also on the refractoriness of dorsal column fibres. They also provide further evidence for specific features of afferent fibres traversing the dorsal columns previously linked to properties of their branching regions.

The plasticity of nerve fibers: the prolonged effects of polarization of afferent fibers.

The review surveys various aspects of the plasticity of nerve fibers, in particular the prolonged increase in their excitability evoked by polarization, focusing on a long-lasting increase in the excitability of myelinated afferent fibers traversing the dorsal columns of the spinal cord. We review the evidence that increased axonal excitability 1) follows epidurally applied direct current (DC) as well as relatively short (5 or 10 ms) current pulses and synaptically evoked intrinsic field potentials; 2) critically depends on the polarization of branching regions of afferent fibers at the sites where they bifurcate and give off axon collaterals entering the spinal gray matter in conjunction with actions of extrasynaptic GABAA membrane receptors; and 3) shares the feature of being activity-independent with the short-lasting effects of polarization of peripheral nerve fibers. A comparison between the polarization evoked sustained increase in the excitability of dorsal column fibers and spinal motoneurons (plateau potentials) indicates the possibility that they are mediated by partly similar membrane channels (including noninactivating type L Cav++ 1.3 but not Na+ channels) and partly different mechanisms. We finally consider under which conditions transspinally applied DC (tsDCS) might reproduce the effects of epidural polarization on dorsal column fibers and the possible advantages of increased excitability of afferent fibers for the rehabilitation of motor and sensory functions after spinal cord injuries.NEW & NOTEWORTHY This review supplements previous reviews of properties of nerve fibers by surveying recent experimental evidence for their long-term plasticity. It also extends recent descriptions of spinal effects of DC by reviewing effects of polarization of afferent nerve fibers within the dorsal columns, the mechanisms most likely underlying the long-lasting increase in their excitability and possible clinical implications.

Branching points of primary afferent fibers are vital for the modulation of fiber excitability by epidural DC polarization and by GABA in the rat spinal cord.

The aim of the study was to examine whether the sustained increases in the excitability of afferent fibers traversing the dorsal columns evoked by their polarization depend on the branching points of these fibers. To this end, the effects of epidural polarization were compared in four spinal regions in deeply anesthetized rats; two with the densest collateralization of muscle afferent fibers (above motor nuclei and Clarke's column) and two where the collateralization is more sparse (rostral and caudal to motor nuclei, respectively. The degree of collateralization in different segments was reconstructed in retrogradely labeled afferent fibers in the rat. Nerve volleys evoked in peripheral nerves by electrical stimulation of the dorsal columns within these regions were used as a measure of the excitability of the stimulated fibers. Potent increases in the excitability were evoked by polarization above motor nuclei and Clarke's column, both during constant direct current (DC) polarization (1 µA for 1 min) and for at least 30 min following DC polarization. Smaller excitability increases occurred during the polarization within other regions and were thereafter either absent or rapidly declined after its termination. The postpolarization increases in excitability were counteracted by the GABAA receptor antagonist bicuculline and the α5GABAA extrasynaptic receptor antagonist L655708 and enhanced by the GABAA receptor agonist muscimol and by ionophoretically applied GABA. As extrasynaptic α5GABAA receptors have been found close to Na channels within branching points, these results are consistent with the involvement of branching points in the induction of the sustained postpolarization increases in fiber excitability.NEW & NOTEWORTHY Polarization of sensory fibers traversing dorsal columns of the spinal cord may considerably increase the excitability of these fibers. We show that this involves the effects of current at branching points of afferent fibers and depends on extrasynaptic effects of GABA. These results contribute to our understanding of the mechanism underlying plasticity of activation of nerve fibers and may be used to increase the effectiveness of epidural stimulation in humans and recovery of spinal functions.

Laser induced damage in coatings for cryogenic Yb:YAG active mirror amplifiers.

We report results of a study of the laser induced damage threshold (LIDT) behavior of ion beam sputtered HfO2/SiO2 multilayer coatings on Yb:YAG using 1-on-1 and N-on-1 test protocols. The tests were conducted at ambient, vacuum, and cryogenic conditions using 280 ps pulses at λ=1030nm. The 1-on-1 LIDT of antireflection (AR) stacks is found to be only slightly reduced under vacuum and cryogenic conditions, while that of high reflectivity (HR) stacks is insensitive to environmental conditions within the uncertainty of the measurements. Cryogenic N-on-1 tests show the LIDT of the HR coating is almost the same as in the 1-on-1 tests. Conversely, the cryogenic N-on-1 test of the AR coating shows damage at ∼13J/cm2, a fluence lower than the 20.4J/cm2 of 1-on-1 tests. The AR damage behavior is found to be affected by imperfections at the Yb:YAG surface. These findings show that high surface quality is required to increase energy extraction from active mirror laser amplifiers.

Influence of short peptides with aromatic amino acid residues on aggregation properties of serum amyloid A and its fragments.

Serum amyloid A variant 1.1 (SAA1.1) is an acute phase protein. In response to injury, inflammation or infection its production increases highly, which may lead to aggregation of the protein and accumulation of its deposits in various organs. Due to the cellular toxicity of the aggregates, as well as the fact that accumulated deposits are a burden that obstructs proper functioning of the affected tissues, it is vital to find a way to suppress the process of pathological aggregates formation. To make this possible, it is necessary to investigate thoroughly the oligomerization process and recognize factors that may influence its course. Some previous studies showed that aromatic interactions are important to the potential of an inhibitor to suppress the aggregation process. In our research we had proved that a five-residue peptide RSFFS (saa1-5) is an efficient inhibitor of aggregation of the most amyloidogenic fragment of SAA1.1, SAA1-12. In the present work the oligomerization and aggregation propensity of SAA1-12 was compared to that of SAA1-27, in order to determine the contribution of the sequence which extends beyond the most amyloidogenic region but encompasses residues reportedly involved in the stabilization of the SAA native conformation. Thioflavin T fluorescence assay, quantitative chromatographic analysis of the insoluble fraction and transmission electron microscopy allowed for a deeper insight into the SAA aggregation process and the morphology of aggregates. Substitutions of Phe3 and/or Phe4 residues in saa1-5 sequence with tryptophan, tyrosine, homophenylalanine, naphthylalanine and ß,ß-diphenylalanine allowed to study the influence of different aromatic systems on the aggregation of SAA1-12 and SAA1-27, and evaluate these results in relation to hSAA1.1 protein. Our results indicate that compounds with aromatic moieties can affect the course of the aggregation process and change the ratio between the soluble and insoluble aggregates.

RNArchitecture: a database and a classification system of RNA families, with a focus on structural information.

RNArchitecture is a database that provides a comprehensive description of relationships between known families of structured non-coding RNAs, with a focus on structural similarities. The classification is hierarchical and similar to the system used in the SCOP and CATH databases of protein structures. Its central level is Family, which builds on the Rfam catalog and gathers closely related RNAs. Consensus structures of Families are described with a reduced secondary structure representation. Evolutionarily related Families are grouped into Superfamilies. Similar structures are further grouped into Architectures. The highest level, Class, organizes families into very broad structural categories, such as simple or complex structured RNAs. Some groups at different levels of the hierarchy are currently labeled as 'unclassified'. The classification is expected to evolve as new data become available. For each Family with an experimentally determined three-diemsional (3D) structure(s), a representative one is provided. RNArchitecture also presents theoretical models of RNA 3D structure and is open for submission of structural models by users. Compared to other databases, RNArchitecture is unique in its focus on structure-based RNA classification, and in providing a platform for storing RNA 3D structure predictions. RNArchitecture can be accessed at http://iimcb.genesilico.pl/RNArchitecture/.

New Peptide-Based Pharmacophore Activates 20S Proteasome.

The proteasome is a pivotal element of controlled proteolysis, responsible for the catabolic arm of proteostasis. By inducing apoptosis, small molecule inhibitors of proteasome peptidolytic activities are successfully utilized in treatment of blood cancers. However, the clinical potential of proteasome activation remains relatively unexplored. In this work, we introduce short TAT peptides derived from HIV-1 Tat protein and modified with synthetic turn-stabilizing residues as proteasome agonists. Molecular docking and biochemical studies point to the α1/α2 pocket of the core proteasome α ring as the binding site of TAT peptides. We postulate that the TATs' pharmacophore consists of an N-terminal basic pocket-docking "activation anchor" connected via a ß turn inducer to a C-terminal "specificity clamp" that binds on the proteasome α surface. By allosteric effects-including destabilization of the proteasomal gate-the compounds substantially augment activity of the core proteasome in vitro. Significantly, this activation is preserved in the lysates of cultured cells treated with the compounds. We propose that the proteasome-stimulating TAT pharmacophore provides an attractive lead for future clinical use.

Ephaptic interactions between myelinated nerve fibres of rodent peripheral nerves.

We report evidence that ephaptic interactions may occur between intact mammalian myelinated nerve fibres and not only between demyelinated or damaged mammalian nerve fibres or nerve cells as analysed in previous studies. The ephaptic interactions were investigated between nerve fibres traversing the lumbar dorsal roots and between bundles of fibres in the sciatic nerve in anaesthetized rats in vivo. The interactions were estimated by comparing the excitability of nerve fibres originating from one of the hindlimb nerves (peroneal or sural) under control conditions and when the stimulation of these fibres was combined with stimulation of another nerve (tibial). An increase in nerve volleys recorded from group I muscle afferents in the peroneal nerve and of the fastest skin afferents in the sural nerve was used as a measure of the increase in the excitability. The excitability of these fibres was increased during a fraction of a millisecond, coinciding with the period of passage of nerve impulses evoked by the conditioning stimulation of the tibial nerve. The degree of the increase was comparable to the increases in the excitability evoked by 1-2 min lasting fibre polarization. Ephaptic interactions were found to be more potent and with longer lasting after-effects within the dorsal roots than within the sciatic nerve. We postulate that ephaptic interactions may result in the synchronization of information forwarded via neighbouring afferent nerve fibres prior to their entry into the spinal cord and thereby securing the propagation of nerve impulses across branching points within the spinal grey matter.

SupeRNAlign: a new tool for flexible superposition of homologous RNA structures and inference of accurate structure-based sequence alignments.

RNA has been found to play an ever-increasing role in a variety of biological processes. The function of most non-coding RNA molecules depends on their structure. Comparing and classifying macromolecular 3D structures is of crucial importance for structure-based function inference and it is used in the characterization of functional motifs and in structure prediction by comparative modeling. However, compared to the numerous methods for protein structure superposition, there are few tools dedicated to the superimposing of RNA 3D structures. Here, we present SupeRNAlign (v1.3.1), a new method for flexible superposition of RNA 3D structures, and SupeRNAlign-Coffee-a workflow that combines SupeRNAlign with T-Coffee for inferring structure-based sequence alignments. The methods have been benchmarked with eight other methods for RNA structural superposition and alignment. The benchmark included 151 structures from 32 RNA families (with a total of 1734 pairwise superpositions). The accuracy of superpositions was assessed by comparing structure-based sequence alignments to the reference alignments from the Rfam database. SupeRNAlign and SupeRNAlign-Coffee achieved significantly higher scores than most of the benchmarked methods: SupeRNAlign generated the most accurate sequence alignments among the structure superposition methods, and SupeRNAlign-Coffee performed best among the sequence alignment methods.

Spinal control of motor outputs by intrinsic and externally induced electric field potentials.

Despite numerous studies on spinal neuronal systems, several issues regarding their role in motor behavior remain unresolved. One of these issues is how electric fields associated with the activity of spinal neurons influence the operation of spinal neuronal networks and how effects of these field potentials are combined with other means of modulating neuronal activity. Another closely related issue is how external electric field potentials affect spinal neurons and how they can be used for therapeutic purposes such as pain relief or recovery of motor functions by transspinal direct current stimulation. Nevertheless, progress in our understanding of the spinal effects of electric fields and their mechanisms has been made over the last years, and the aim of the present review is to summarize the recent findings in this field.

Long-lasting increase in axonal excitability after epidurally applied DC.

Effects of direct current (DC) on nerve fibers have primarily been investigated during or just after DC application. However, locally applied cathodal DC was recently demonstrated to increase the excitability of intraspinal preterminal axonal branches for >1 h. The aim of this study was therefore to investigate whether DC evokes a similarly long-lasting increase in the excitability of myelinated axons within the dorsal columns. The excitability of dorsal column fibers stimulated epidurally was monitored by recording compound action potentials in peripheral nerves in acute experiments in deeply anesthetized rats. The results show that 1) cathodal polarization (0.8-1.0 µA) results in a severalfold increase in the number of epidurally activated fibers and 2) the increase in the excitability appears within seconds, 3) lasts for >1 h, and 4) is activity independent, as it does not require fiber stimulation during the polarization. These features demonstrate an unexplored form of plasticity of myelinated fibers and indicate the conditions under which it develops. They also suggest that therapeutic effects of epidural stimulation may be significantly enhanced if it is combined with DC polarization. In particular, by using DC to increase the number of fibers activated by low-intensity epidural stimuli, the low clinical tolerance to higher stimulus intensities might be overcome. The activity independence of long-lasting DC effects would also allow the use of only brief periods of DC polarization preceding epidural stimulation to increase the effect.NEW & NOTEWORTHY The study indicates a new form of plasticity of myelinated fibers. The differences in time course of DC-evoked increases in the excitability of myelinated nerve fibers in the dorsal columns and in preterminal axonal branches suggest that distinct mechanisms are involved in them. The results show that combining epidural stimulation and transspinal DC polarization may dramatically improve their outcome and result in more effective pain control and the return of impaired motor functions.

Direct current stimulation modulates the excitability of the sensory and motor fibres in the human posterior tibial nerve, with a long-lasting effect on the H-reflex.

Several studies demonstrated that transcutaneous direct current stimulation (DCS) may modulate central nervous system excitability. However, much less is known about how DC affects peripheral nerve fibres. We investigated the action of DCS on motor and sensory fibres of the human posterior tibial nerve, with supplementary analysis in acute experiments on rats. In forty human subjects, electric pulses at the popliteal fossa were used to elicit either M-waves or H-reflexes in the Soleus, before (15 min), during (10 min) and after (30 min) DCS. Cathodal or anodal current (2 mA) was applied to the same nerve. Cathodal DCS significantly increased the H-reflex amplitude; the post-polarization effect lasted up to ~ 25 min after the termination of DCS. Anodal DCS instead significantly decreased the reflex amplitude for up to ~ 5 min after DCS end. DCS effects on M-wave showed the same polarity dependence but with considerably shorter after-effects, which never exceeded 5 min. DCS changed the excitability of both motor and sensory fibres. These effects and especially the long-lasting modulation of the H-reflex suggest a possible rehabilitative application of DCS that could be applied either to compensate an altered peripheral excitability or to modulate the afferent transmission to spinal and supraspinal structures. In animal experiments, DCS was applied, under anaesthesia, to either the exposed peroneus nerve or its Dorsal Root, and its effects closely resembled those found in human subjects. They validate therefore the use of the animal models for future investigations on the DCS mechanisms.

Coarse-grained modeling of RNA 3D structure.

Functional RNA molecules depend on three-dimensional (3D) structures to carry out their tasks within the cell. Understanding how these molecules interact to carry out their biological roles requires a detailed knowledge of RNA 3D structure and dynamics as well as thermodynamics, which strongly governs the folding of RNA and RNA-RNA interactions as well as a host of other interactions within the cellular environment. Experimental determination of these properties is difficult, and various computational methods have been developed to model the folding of RNA 3D structures and their interactions with other molecules. However, computational methods also have their limitations, especially when the biological effects demand computation of the dynamics beyond a few hundred nanoseconds. For the researcher confronted with such challenges, a more amenable approach is to resort to coarse-grained modeling to reduce the number of data points and computational demand to a more tractable size, while sacrificing as little critical information as possible. This review presents an introduction to the topic of coarse-grained modeling of RNA 3D structures and dynamics, covering both high- and low-resolution strategies. We discuss how physics-based approaches compare with knowledge based methods that rely on databases of information. In the course of this review, we discuss important aspects in the reasoning process behind building different models and the goals and pitfalls that can result.

Evidence that some long-lasting effects of direct current in the rat spinal cord are activity-independent.

The effects of trans-spinal direct current (DC) stimulation (tsDCS) on specific neuronal populations are difficult to elucidate, as it affects a variety of neuronal networks. However, facilitatory and depressive effects on neurons processing information from the skin and from muscles can be evaluated separately when weak (0.2-0.3 µA) DC is applied within restricted areas of the rat spinal cord. The effects of such local DC application were recently demonstrated to persist for at least 1 h, and to include changes in the excitability of afferent fibres and their synaptic actions. However, whether these effects require activation of afferent fibres in spinal neuronal pathways during DC application, i.e. whether they are activity-dependent or activity-independent, remained an open question. The aim of the present study was to address this question by analysing the effects of local DC application on monosynaptic actions of muscle and skin afferents (extracellular field potentials) and afferent fibre excitability. The results revealed that long-lasting post-polarization changes evoked without concomitant activation of afferent fibres replicate changes evoked by stimuli applied during, before and after polarization. The study leads to the conclusion that the reported effects are activity-independent. As this conclusion applies to the local effects of DC application in at least two spinal pathways and to the effects of both cathodal and anodal polarization, it indicates that some of the more widespread effects of trans-spinal and trans-cranial stimulation (both tsDCS and transcranial DC stimulation) may be activity-independent. The results may therefore contribute to the design of more specific DC applications in clinical practice.

Designing peptidic inhibitors of serum amyloid A aggregation process.

Amyloid A amyloidosis is a life-threatening complication of a wide range of chronic inflammatory, infectious and neoplastic diseases, and the most common form of systemic amyloidosis worldwide. It is characterized by extracellular tissue deposition of fibrils that are composed of fragments of serum amyloid A protein (SAA), a major acute-phase reactant protein, produced predominantly by hepatocytes. Currently, there are no approved therapeutic agents directed against the formation of fibrillar SAA assemblies. We attempted to develop peptidic inhibitors based on their similarity and complementarity to the regions critical for SAA self-association, which they should interact with and block their assembly into amyloid fibrils. Inh1 and inh4 which are comprised of the residues from the amyloidogenic region of SAA1.1 protein and Aß peptide, respectively, were found by us as capable to significantly suppress aggregation of the SAA1-12 peptide. It was chosen as an aggregation model that mimicks the amyloidogenic nucleus of SAA protein. We suppose that aromatic interactions may be responsible for inhibitory activity of both compounds. We also recognized that aromatic residues are involved in self-association of SAA1-12.

[Spread of nano-objects in the air as a result of switching-on a microwave]. / Rozprzestrzenianie sie w powietrzu nanoobiektów wytwarzanych w wyniku wlaczenia kuchenki mikrofalowej.

BACKGROUND: Switching-on a microwave results in the creation of nano-sized particles, which can spread through the air of a given premise, e.g., room. MATERIAL AND METHODS: The study was carried out to determine the number and surface concentrations as well as the mean particles size using a DiscMini measurement device distributed in 6 measuring points to track changes of particle parameters, primarily at the source of particle creation and in the area of local ventilation (fume cupboard), and also in other places, e.g., near the window or in the middle of the room. RESULTS: Where the fume cupboard was switched-off, i.e., normal pressure ventilation in the room, switching-on the microwave caused a 9.42-14.14-fold increase in the number concentration of nano-sized particles relative to the background and a 3.51-4.81-fold increase in the surface concentration. Where the fume cupboard was switched-on, i.e., negative pressure ventilation in the room switching-on the microwave caused a 3.20-4.43-fold increase in the number concentration of nano-size particles relative to the background and a 1.61-1.89-fold increase in the surface concentration. CONCLUSIONS: The analysis of the data shows that switching-on a microwave for 5 min results in the creation of nano-objects already after about 3 min with the maximum concentration values after 12 min since switching-on the microwave in all 6 measurement points distributed in the test room. This applies to both situations, i.e., when the fume cupboard was switchedoff or switched-on. Med Pr 2016;67(3):353-363.

Facilitation of ipsilateral actions of corticospinal tract neurons on feline motoneurons by transcranial direct current stimulation.

Ipsilateral actions of pyramidal tract (PT) neurons are weak but may, if strengthened, compensate for deficient crossed PT actions following brain damage. The purpose of the present study was to examine whether transcranial direct current stimulation (tDCS) can strengthen ipsilateral PT (iPT) actions; in particular, those relayed by reticulospinal neurons co-excited by axon collaterals of fibres descending in the iPT and contralateral PT (coPT) and of reticulospinal neurons descending in the medial longitudinal fascicle (MLF). The effects of tDCS were assessed in acute experiments on deeply anaesthetized cats by comparing postsynaptic potentials evoked in hindlimb motoneurons and discharges recorded from their axons in a ventral root, before, during and after tDCS. tDCS was consistently found to facilitate joint actions of the iPT and coPT, especially when they were stimulated together with the MLF. Both excitatory postsynaptic potentials and inhibitory postsynaptic potentials evoked in motoneurons and the ensuing ventral root discharges were facilitated, even though the facilitatory effects of tDCS were not sufficient for activation of motoneurons by iPT neurons alone. Facilitation outlasted single tDCS periods by at least a few minutes, and the effects evoked by repeated tDCS by up to 2 h. The results of this study thus indicate that tDCS may increase the contribution of iPT actions to the recovery of motor functions after injuries to coPT neurons, and thereby assist rehabilitation, provided that corticoreticular and reticulospinal connections are preserved.