, 2003) Thus, the PW may activate a fractionally higher number o

, 2003). Thus, the PW may activate a fractionally higher number of synapses on proximal dendrites as compared to the SW (Lübke and Feldmeyer, 2007; Petreanu et al., 2009). For L2/3 pyramidal neurons of the visual cortex, it has been shown that STDP tends to induce lower levels of LTP in distal dendritic inputs (Froemke et al., 2005). This is possibly due to a strong attenuation of back-propagating APs toward distal dendrites (Sjöström et al., 2008), resulting in lower NMDAR activation levels in apical as compared to basal dendrites. In the barrel cortex such a mechanism could render SW-associated synapses less sensitive to STDP. Differences in clustering or functionality of synapses

may also cause contrasting levels of plasticity (Humeau et al., 2005), but it is as yet unclear if such differences exist between PW- and SW-associated inputs (Varga et al., 2011). Lateral or vertical forward inhibition (Adesnik and Scanziani, selleck screening library 2010; Chittajallu and Isaac, 2010; House et al., 2011; Kimura et al., 2010; Swadlow and Gusev, 2002) could further sculpt the differences between PW- and SW-associated excitatory pathways. In our study the inhibitory/excitatory conductance ratio was slightly but significantly higher for SW-evoked responses as compared to PW-evoked responses (Figures 6 and 7). In addition the inhibitory currents preceded on average the excitatory currents

for the SW, whereas find more for the PW the inhibitory currents occurred after excitation. This prompts the speculation that the SW recruits a different or an additional and slightly more potent inhibitory PAK6 circuit, which may efficiently constrain the temporal summation of EPSPs (Pouille and Scanziani, 2001) or shunt back-propagating APs (Tsubokawa and Ross, 1996) and contribute to the insensitivity to forms of plasticity. In support of this we found that a block of GABAergic inputs greatly facilitated SW-driven STD-LTP (Figure 8).

Altogether, it is likely that differences in both excitatory and inhibitory pathways render the SW-associated inputs less permissive to STD-LTP than the PW-associated synapses. We showed that trimming of all except two neighboring whiskers facilitated the induction of SW-driven STD-LTP (Figure 5). This is in line with an ex vivo study in which across-barrel STD-LTP was facilitated after deprivation (Hardingham et al., 2011). Whisker trimming did not change the baseline levels of SW- and PW-evoked responses at the population level. However, the average SW/PW ratio had increased for most cells (Figure 4). Because the recorded neurons were current clamped above the inhibitory reversal potential (Ei = −100mV), this could have been caused by a reduction in SW-associated inhibition (Kelly et al., 1999). Alternatively, excitatory synapses from surround inputs could have been potentiated (Glazewski et al., 2000). Interestingly, DWE did not block or occlude STD-LTP for either the PW or SW.

Other mechanisms that additionally contribute to Ca2+-dependent R

Other mechanisms that additionally contribute to Ca2+-dependent RRP recovery include, for example, CaM independent signaling to the priming machinery, e.g., via the C1 and C2 domains of Munc13s (Rhee et al., 2002; Shin et al., 2010), or facilitation of the release of reluctant RG7420 mw vesicles following elevation of [Ca2+]i (Wu and Borst,

1999). The SSD levels during high-frequency synaptic activity are thought to be defined by a balance between SV release and replenishment (Dittman and Regehr, 1998; Saviane and Silver, 2006; Wang and Kaczmarek, 1998). We therefore expected that the reduction of RRP replenishment rates seen in Munc13-1W464R KI calyces (Figures 3 and 4) would result in lower SSD levels. However, a reduction of SSD levels was

only found in calyces of more mature KI animals, whereas in WT and Munc13-1W464R calyces at P9–P11 SSD was similar at all frequencies tested (Figure 6). This is surprising in view of the findings that acute application of CaM inhibitors causes lower SSD levels in the rat calyx of Held at P9–P11 (Hosoi et al., 2007; Lee et al., 2012; Sun et al., 2006) and that cultured hippocampal neurons expressing only Munc13-1W464R Doxorubicin in vivo from a viral rescue construct show an increased STD and lower SSD levels (Junge et al., 2004). At least four scenarios may account for this unexpected finding. First, basal, Ca2+-independent activity of Munc13-1 (Basu et al., 2005) in the Munc13-1W464R mutant might be sufficient to maintain normal SSD levels during phases of moderate to strong synaptic activity, but not upon complete RRP depletion by sustained presynaptic depolarization. Second, the priming activity of Munc13-1W464R can still be strongly potentiated via the C1 domain or the C2B domain (Rhee

et al., 2002; Shin et al., 2010). Third, it is possible that the regulation of Munc13-1 activity by CaM in the calyx of Held in vivo is mainly relevant at tuclazepam rather high [Ca2+]i. Indeed, the dual pulse protocol we used to assess the replenishment of the fast and slowly releasable SV pools (Figures 3 and 4) involves long depolarizations, during which global presynaptic Ca2+-concentrations are expected to reach higher levels than during AP trains (Hosoi et al., 2007). In addition, an effect of the Munc13-1W464R mutation on the evoked synaptic responses was seen during recovery from synaptic depression after high-frequency stimulation trains, which likely cause a strong and long-lasting rise in [Ca2+]i (Figures 5A–5D). The notion that the Ca2+-CaM-Munc13-1 signaling may be only operational at rather high [Ca2+]i in intact cells is supported by a recent study on the calyx of Held (Lee et al.

, 2001) Acute subcutaneous administration of sumatriptan activat

, 2001). Acute subcutaneous administration of sumatriptan activates Sirolimus the pituitary-adrenal axis: significant increases in β-endorphin and cortisol concentrations are reported across all subjects receiving sumatriptan (Facchinetti et al., 1994), and these would produce secondary effects. Migraine medications may also alter sensory processing. For example, the administration of sumatriptan to healthy volunteers produces abnormal psychophysiological (diminished pleasantness) and fMRI signal (in anterior insular, lateral orbitofrontal, and anterior cingulate cortices

and medial thalamus) changes that are observed only following sumatriptan, not saline (Krämer et al., 2007). In addition to exogenously administered drugs, endogenous chemical (hormonal) milieu can also be a significant issue in migraine. About 17% of women versus 6% of men get migraines (Rasmussen et al., 1991). Perhaps the best example of induced stressors on brain systems is the female menstrual cycle (Farage et al., 2008). Menstrual migraine (MM) is common in women and may relate to hormonal modulations in the GABA-A receptors decreasing normal inhibitory control (Epperson et al., 2002). Menstrual migraine may be more difficult to treat than nonmenstrual

migraine in women, suggesting a role of induced resistance as a result of their hormonally induced migraine. Menstrual migraine may also be a contributor to the evolution of chronification of headache (Lay and Broner, 2008). Conversely, elimination of MM with the use of hormonal preventive medications can be achieved in a large percentage GSI-IX molecular weight of patients, and this further decreases chronic migraine that is present in over 90% of women (Calhoun and Ford, 2008). It would thus seem that the alterations induced in brain systems that induce menstrual migraine may add to the allostatic load/overload. Estrogen (estradiol) and progesterone

(via allopregnanolone) affect neuronal systems with opposite effects, with estrogen generally being excitatory—enhancing glutamatergic systems and progesterone inhibitory—through GABA systems (Finocchi and Ferrari, 2011). Progesterone usually antagonizes estradiol in synaptic remodeling in brain regions, including the hippocampus (Wong et al., unless 2009). Increased brain sensitivity in women includes catamenial epilepsy, in which hormonal changes, particularly estrogen, contribute to increased seizures (Guille et al., 2008). A similar process may take place in migraine. The effects of estradiol on brain systems is complex and may induce excitatory-induced neuronal changes (Blacklock et al., 2005) but may also be protective of adrenal steroids (Garcia-Segura et al., 2007). The higher prevalence of stress-related disorders in women may relate to estrogen effects on brain systems that have high levels of both genomic and nongenomic estrogen receptors (viz.

5 μg/ml function-blocking goat anti-rat NRP1 antibody or control

5 μg/ml function-blocking goat anti-rat NRP1 antibody or control IgG was added. The angle turned by the growth cone was calculated using Image J. Statistical comparisons were made using a Mann-Whitney U test. We thank Drs. A.L. Kolodkin, D.D. Ginty, C. Gu, H. Fujisawa, J. Rossant, G.H. Fong, and M. Taniguchi for mouse strains; the staff of the Biological

Resources Unit at the UCL Institute of Ophthalmology for help with mouse husbandry; the Institute of Medical Sciences Microscopy and Imaging Facility for help with confocal microscopy; and Kathryn Davidson, Heather Walker, and Andrew Peace for technical assistance. This research was funded by a Wellcome Trust Project Grant to L.E. and C.R. (reference 085476) and a Central VX-809 manufacturer Research Fund grant from the University of London to C.R. (reference AR/CRF/B). “
“During developmental wiring of the nervous system, axons respond to attractive and repulsive guidance cues to navigate to their targets. Surprisingly, only a small number of guidance cues have been identified so far, suggesting that additional chemoattractants and repellents remain to be discovered. A well-known model system to study axon guidance is the spinal cord ventral midline. During development, commissural neurons, located in the dorsal spinal cord, send axons that project toward and subsequently across the floor plate, a find more specialized structure at the ventral midline, which acts as an intermediate target and influences commissural axons

by expressing attractive and repulsive cues (Dickson and

Zou, 2010). The first midline guidance cue identified, Netrin-1, has two distinct activities on precrossing commissural axons: it stimulates growth and attracts these axons toward the floor plate (reviewed in Charron and Tessier-Lavigne, 2005). Precrossing commissural axons are also guided by Sonic hedgehog (Shh), which chemoattracts commissural axons without stimulating their growth (Charron et al., 2003). Although Shh and Netrin-1 are required for normal guidance of commissural axons, intriguingly, when dorsal spinal cord explants are exposed to Netrin-1-deficient floor plates in the presence of Shh signaling inhibitors, some commissural axons are Bay 11-7085 still attracted (Charron et al., 2003). This suggests that the floor plate secretes other chemoattractants than Netrin-1 and Shh. However, the molecular nature of these floor plate-derived attractant guidance cues remains unknown. Increasing evidence indicates that vascular endothelial growth factor A (VEGF-A, termed VEGF from hereon), a prototypic angiogenic factor, plays a key role in the nervous system (Ruiz de Almodovar et al., 2009). For instance, VEGF promotes proliferation, migration, differentiation and survival of neuroblasts (Jin et al., 2002, Wittko et al., 2009 and Zhang et al., 2003), and induces axonal outgrowth of various neurons (Ruiz de Almodovar et al., 2009). By activating its signaling receptor Flk1, VEGF chemoattracts cerebellar granule cells (Ruiz de Almodovar et al.

All released and recycling fractions are expressed as percent of

All released and recycling fractions are expressed as percent of the total vesicle pool. Anatomically, the total number of vesicles at a synapse is correlated with bouton volume (Knott et al., 2006; Murthy et al., 2001). Vesicular release, on the other hand, is restricted to the active zone at the surface of the bouton. Linear scaling has been demonstrated between Pr and the number of surface-docked vesicles (Murthy et al., 2001). Therefore, the most straightforward assumption would be linear scaling between the number of released vesicles (R) and bouton surface area (A): R = k × A (with k being a proportionality factor), equivalent to a 2/3-power scaling with

bouton volume (V): R = k × V2/3. If all vesicles were functional, RG7420 mw V could be substituted with the total number of vesicles (ves) filling the selleck kinase inhibitor volume of the bouton. In this case, RF would be expected

to scale as RF = k × ves−1/3. As shown in Figure 3B (black curve), this surface-to-volume function fits our data well (RF = 172 × ves−1/3). Data are reported as mean ± SEM unless indicated otherwise. To test for significance between population means, we used the two-tailed Student’s t test. As nonparametric measures of absolute and relative dispersion of single bouton data, we use the interquartile range (IQR): Q75% − Q25% and the quartile coefficient of variation (QCV): (Q75% − Q25%) / (Q75% + Q25%), respectively. All correlations are expressed as squared Pearson’s correlation coefficients (R2). Statistical significance was assumed when p < 0.05. Boundaries used for assigning significance in figures: not significant (n.s.), p > 0.05; significant, p < 0.05 (∗), p < 0.01 (∗∗), and p < 0.001 (∗∗∗). This work was supported by the Novartis Research Foundation,

isothipendyl SystemsX.ch, and the Kavli Foundation. The authors thank Daniela Gerosa for excellent technical assistance; Yongling Zhu and Charles F. Stevens for the gift of sypHluorin-1X; Roger Y. Tsien for tdimer2; and Corette Wierenga, Volker Scheuss, and the members of the Oertner lab for critically reading the manuscript. “
“Determination of the functional significance of network modules such as columns and barrels in the mammalian brain has been an ongoing topic of research (Mountcastle, 1997). One of the primary research questions has centered around understanding the similarities and differences in the response properties of neurons within the modules (Linden and Markram, 2003). Due to difficulties in simultaneously capturing the morphologies, connectivities, and functional activities of individual neurons, it remains unclear how these neurons that are part of a module interact with each other and contribute to modular network outputs.

Early physiological recordings suggested that there were four typ

Early physiological recordings suggested that there were four types of bipolar cells: ON, OFF, sustained, and transient (Kaneko, 1970; Werblin and Dowling, 1969). Modern anatomical work and subsequent physiological evidence indicate that the true number of bipolar cell types is about 12. This has been a gradual realization. Initial studies used synapse densities (Cohen and Sterling, 1990) to distinguish the types. As marker proteins of increasing specificity

were discovered, the number of putative bipolar cell types gradually increased. Recent studies seem to have brought this to its conclusion. A set of intersecting methods find more was used to classify the bipolar cells of the rabbit (MacNeil et al., 2004). The strategy was to seek a complete survey of bipolar cell types by using several methods with different sampling biases. For purposes of classification, the purely anatomical Anti-diabetic Compound Library cell line samples were complemented by a set of cells injected with Lucifer yellow after physiological recording, so that their responses to light could be used as part of the classification. The bipolar cells of the rabbit were divided into a rod bipolar cell and 12 types of cone bipolar cells. In near-perfect agreement, Wässle et al. (2009) classified

the bipolar cells of the mouse using immunostaining for recently discovered type-specific markers and transgenic strains in which one or a few types of bipolar cells express a fluorescent marker. These were supplemented by microinjection, to reveal the cells’ finest processes and their contacts. They found one type of rod Levetiracetam driven bipolar cell and 11 types that receive inputs primarily from cones (Figure 2). Because they are population stains, these methods allowed an estimate of the total number of bipolar cells of each type, which could

then be added up for comparison with the total number of bipolar cells known by independent methods to exist in the mouse (Jeon et al., 1998). The identified individual cell types correctly added up to the known total number of bipolar cells. Thus, “…the catalog of 11 cone bipolar cells and one rod bipolar cell is complete, and all major bipolar cell types of the mouse retina appear to have been discovered” (Wässle et al., 2009). This concept is simple, but it is topologically fairly subtle (Figure 3). From partial evidence, it was suspected a decade ago that each cone makes output to each of the types of bipolar cells—a critical principle for the signal processing of the retina. Wässle et al. (2009) could confirm that this occurs for each of the 11 types of bipolar cells that they identified in the mouse. The exception is a specialized “blue cone bipolar,” which selectively contacts the short wavelength sensitive cones, as is necessary if the chromatic information is not to be degraded. Symmetrically, some bipolar cells avoid the terminals—they are numerically infrequent—of blue cones. And there is some crosstalk with the rods.

(2011) presents an intriguing hypothesis on the modulation of mor

(2011) presents an intriguing hypothesis on the modulation of morphine analgesia by heterodimerization of DORs with MORs. It pulls together and confirms prior observations and extends them to provide an explanation for how DORs modulate morphine actions. It represents a significant step forward in our understanding of the basic mechanisms underlying various aspects of opioid tolerance. Like most good science, it also raises a number of issues that need to be addressed in the future. Some of these involve trans-isomer purchase MOR-1 splice variants, both the full length ones that can potentially dimerize with DORs and the

truncated single TM ones that may have actions similar to those seen with MORTM1-TAT. However, it is important to remember that tolerance learn more is like a tug of war, with heterodimerization representing only a single person pulling on the rope. “
“Because neurons communicate electrically, neuroscience has traditionally relied on measurements of the membrane potential using electrodes.

But because electrodes are mechanically invasive, there are scant data on how different parts of a neuron interact or how assemblies of neurons communicate. As an example of this limitation, it is not possible to measure the electrical properties of dendritic spines, the primary sites for excitatory input in the brain, with electrodes because spines are simply too small for current electrodes. Electrical recordings also have significant limitations in studies of the thousands Thymidine kinase of cells that form neuronal microcircuits, where only highly invasive electrode arrays can be used to record the ensemble’s electrical activity. Optical techniques, however, seem to be an ideal solution for measuring membrane potentials, for both spines and circuits, since they are relatively noninvasive and could work both at low and high magnification. While voltage imaging in neuroscience has a long history and has

provided many significant advances in neuronal biophysics and circuit function (reviewed in Cohen, 1989 and Cohen and Lesher, 1986), our belief is that it has not yet achieved its full potential, particularly for the study of mammalian preparations. As Sherlock Holmes argued, to understand a situation one needs to evaluate not only was has happened but also what has not happened. In this case, we find it useful to compare current voltage imaging methods with calcium imaging to understand what could be missing. For example, calcium indicators are very sensitive ( Tsien, 1980) and have custom-tailored spectroscopic properties ( Grynkiewicz et al., 1985). They can be noninvasively loaded into neurons ( Tsien, 1981) and can be genetically encoded ( Miyawaki et al., 1997).

The response of cells to fimbria or thalamus single-pulse stimula

The response of cells to fimbria or thalamus single-pulse stimulation 50 ms following single-pulse stimulation of the PFC was also considered in a subgroup of cells (n =

13). In some cases (n = 12), we injected depolarizing current through the recording electrode (between −0.2 and 0.2 nA) to record an F1 or T1 response during a depolarized membrane potential similar to that at which F2 and T2 responses were evoked. A subset of cells (n = 13) was also subjected to a stimulus protocol in which a single-pulse stimulus was delivered to the PFC (1.0 mA; 0.5 ms; PFC1), followed at a 500 ms latency by a train stimulation of the fimbria or thalamus (50 Hz train of ten pulses; 1.0 mA; 0.5 ms), after which a second pulse was delivered to the PFC (1.0 mA; 0.5 ms; PFC2). In all cases, responses to stimulation were averaged over all of the repetitions selleckchem delivered to the cell. To calculate the magnitude of EPSP suppression, we first determined the Cilengitide cost ratio of the control and test pulses. For instance, in the cases in which we stimulated the fimbria, we calculated F2/F1 using response amplitudes. As this quotient represents the proportion of the response retained following PFC train stimulation, we expressed the difference between 1 and F2/F1 as a percentage to indicate the magnitude of EPSP suppression. After baseline

and stimulus-response recordings were collected, cells were filled with Neurobiotin by passing positive current (1 nA, 200 ms pulses, 2 Hz) for at least 10 min through the recording electrode. Upon completion of recording experiments, animals unless were euthanized with an overdose of sodium pentobarbital (100 mg/kg) and transcardially perfused with cold saline followed by 4% paraformaldehyde. Brains were then removed and postfixed in 4% paraformaldehyde for at least 24 hr before being transferred to a 30% sucrose solution in 0.1 M phosphate buffer. After at least 48 hr in sucrose, brains were cut into 50 μm sections using a freezing microtome and placed

into phosphate buffer. Sections through PFC and fimbria or thalamus were mounted on gelatin-coated slides and Nissl stained to verify placement of stimulating electrodes. Sections through VS were processed for visualization of Neurobiotin-filled cells and then mounted on gelatin-coated slides and Nissl stained. All stained slides were coverslipped and examined microscopically for cell and electrode location. This work was supported by grants from the National Institutes of Health (R01 MH060131) to P.O.’D. and (R31 MH092043) to G.G.C. “
“Coordinated movement relies on the integration of sensory feedback signals with core motor circuits. In mammals, motor performance is refined by sensory feedback signals that convey information from proprioceptive afferents as well as from mechanoreceptive afferents activated by diverse cutaneous receptors.

, 1998, Single and Borst, 1998 and Single et al , 1997) However,

, 1998, Single and Borst, 1998 and Single et al., 1997). However, it is unclear if the computational nodes of the HR-EMD, the delay filter and the multiplier, correspond

to individual cell types, or if motion detection is computed in a more distributed manner, with distinct contributions from many different neurons. It is also possible that there are multiple circuits dedicated to motion computation; different neuron types could extract specific visual features, as in vertebrate retinal ganglion Selleckchem Ibrutinib cells (Gollisch and Meister, 2010), and compute motion independently within parallel channels. Indeed, several recent studies suggest that fly motion vision may be segregated into parallel, functionally distinct channels (Clark et al., 2011, Eichner et al., 2011, Joesch et al., 2010, Katsov and Clandinin, 2008 and Rister et al., 2007). The fly visual system consists of four ganglia NVP-BGJ398 supplier called the lamina, medulla, lobula, and lobula plate (Figure 1A), which together are referred to as the optic lobes. As the first

synaptic relay between the photoreceptors and motion-sensitive tangential neurons in the lobula plate, it has been hypothesized that the early stages of motion computation may occur in the lamina (Coombe et al., 1989 and Douglass and Strausfeld, 1995). The lamina is organized into an array of ∼750 retinotopic “cartridges,” each of which corresponds to a discrete sample of the visual world, ∼5° in Drosophila ( Braitenberg, Thalidomide 1967, Buchner, 1971 and Kirschfeld, 1967). The anatomy and connectivity of lamina neurons is known in exquisite detail, owing to detailed Golgi studies ( Fischbach and Dittrich, 1989) and electron microscopy (EM) reconstructions ( Meinertzhagen and O’Neil, 1991 and Rivera-Alba et al., 2011). Six light-sensitive photoreceptors, R1–R6, project their axons into each lamina cartridge. Two other photoreceptor neurons, R7 and R8, pass through the lamina and synapse in specific layers of the medulla. Besides

the photoreceptor axons, the lamina also contains processes of 12 other neuronal cell types (Figures 1C and 1D). These lamina-associated neurons include five lamina output neurons, six putative feedback neurons, and one lamina intrinsic cell (Fischbach and Dittrich, 1989). Eight of these neuron classes are columnar—there is one cell per retinotopic column (Figure 1C). The columnar neurons include the feedforward lamina monopolar cells, L1–L5 (Figure 1C, red), which send axonal processes into the medulla. The largest of the monopolar cells, L1, L2, and L3, receive direct synaptic input from the R1–R6 photoreceptors, but L4 and L5 do not (Meinertzhagen and O’Neil, 1991 and Rivera-Alba et al., 2011). In addition to these five lamina output neurons, three putative feedback neurons, T1, C2, and C3, are also columnar (Figure 1C, blue).

5 s The pulse width and frequency of stimulation were selected t

5 s. The pulse width and frequency of Modulators stimulation were selected to optimise the strengthening benefits

of the electrical stimulation (Bowman and Baker 1985). The amplitude of electrical stimulation was set at a level to produce maximum tolerable muscle contractions. If participants were unable to indicate tolerable levels of stimulation, the minimum amplitude of stimulation required to generate a palpable muscle contraction was used. At the beginning of each session, participants were instructed to contract the wrist and finger extensor muscles in time with the electrical stimulation. Participants were reminded regularly during each www.selleckchem.com/products/VX-770.html training session but not verbally encouraged with each contraction. Both the experimental and control groups wore hand splints for 12 hours a day, 5–7 days per week. Custom-made hand splints were used to maintain the maximum tolerated wrist

and finger extension. The splints were checked each time they were applied and modified as required to maintain comfort, fit, and stretch. During the 2-week follow-up period, participants in both groups continued to wear the hand splint for 12 hours a day, 5–7 days per week. Electrical stimulation was not applied to the wrists of participants in either group during these 2 weeks. A diary was used to record the duration and frequency of electrical stimulation and splinting. The electrical stimulation and usual care were administered by physiotherapists working in the participating units over the course of the trial. These physiotherapists were not randomised to participants and consequently learn more they managed an arbitrary

mix of control and experimental participants. The splints were applied by physiotherapists, nursing staff, or physiotherapy assistants (under the supervision of the treating physiotherapists). Throughout the study, no other stretch-based interventions were administered to the wrist. All participants received usual multidisciplinary rehabilitation provided by the participating units, which included training of hand function as appropriate. No botulinum toxin was administered to the wrist prior to or during the study period. Use of other anti-spasticity medication was not mandated by the trial protocol and was recorded. There were one primary Rolziracetam and six secondary outcomes. The primary outcome was passive wrist extension measured with a torque of 3 Nm and with fingers in extension. This was used to reflect the extensibility of the extrinsic wrist and finger flexor muscles. The secondary outcomes were: passive wrist extension with a torque of 2 Nm, strength of the wrist and finger extensor muscles, spasticity of the wrist flexor muscles, motor control of the hand, physiotherapists’ and participants’ Global Perceived Effect of Treatment, and perception of treatment credibility.