On the

other hand, the brain areas implicated in anxiety disorders include the amygdala, insula, and anterior cingulate cortex (Craske et al., 2009; Hartley and Phelps, 2012). In addition, excessive rumination and negative self-referential memory observed in depressed individuals might be linked to the function of the default network. Indeed, the default network is overactive in individuals with depression when they are evaluating emotional stimuli (Sheline et al., 2009), and its activity is correlated with the level of depressive rumination (Hamilton et al., 2011). To the extent that the default network contributes to task-relevant mental simulation and spontaneous cognition (Andrews-Hanna et al., 2010), this might also account for the fact that depressed individuals perform better find more in sequential decision-making tasks and analytical thinking (Andrews and Thomson, 2009; von Helversen et al., 2011). Patients with depression display increased metabolic activity in the

subgenual cingulate cortex, and deep brain stimulation of the same brain area produces therapeutic I-BET151 cost effects (Mayberg et al., 2005). Therefore, the functional coupling between the subgenual cingulate cortex and the default network patients, which is greater in patients with depression (Greicius et al., 2007), might correspond to the interface between excessive self-referential thoughts and their negative emotional consequences. As reviewed recently (Paulus and Yu, 2012), a large number of studies have examined the performance of individuals with depression or anxiety during the Iowa gambling task (Bechara et al., 1997), but the results from these studies were inconsistent. Obtaining

the best outcome during the Iowa gambling task depends on a number of computationally distinct processes, including reinforcement learning, ADAMTS5 risk preference, and loss aversion (Fellows and Farah, 2005; Worthy et al., 2012). Understanding how each of these processes is influenced in individuals with depression or anxiety therefore still remains an important research area (Angie et al., 2011; Hartley and Phelps, 2012). The available results suggest that individuals with anxiety disorders are more risk-averse than control subjects (Maner et al., 2007), whereas the neural signals related to reinforcement might be reduced, especially in the striatum, in depressed individuals (Pizzagalli et al., 2009). Although neurochemical basis of mood and anxiety disorders remains poorly understood, much attention has been focused on the possible role of altered serotonin metabolism in depression (Dayan and Huys, 2009). For example, it has been hypothesized that future reward might be discounted excessively in individuals with depression due to an abnormally low level of serotonin (Doya, 2002). In fact, the discount rate used to calculate the subjective value of future reward might be controlled by serotonin (Schweighofer et al., 2008).

We therefore propose that selleck chemical VEGF-A is a positive signal for RGC axons and one of the long-sought-after midline factors that promotes commissural axon crossing at the optic chiasm. Because VEGF is expressed in a broad domain around the chiasm, the VEGF164-mediated promotion of

RGC growth must be balanced by repulsive cues that refine the area of axon crossing. Consistent with this idea, the chemorepellents SLIT1 and SLIT2 define the boundaries of the corridor through which RGC axons migrate at the chiasm midline, and loss of these repellents causes RGC axons to cross the midline in an abnormally broad domain (Erskine et al., 2000 and Plump et al., 2002; Figure 8D). NrCAM modulates neuropilin signaling in response to class 3 SEMAs during commissural axon guidance in the anterior commissure (Falk et al., 2005) and spinal cord (Nawabi et al., 2010). Several lines of evidence argue against the possibility that NrCAM modulates neuropilin signaling in response to VEGF164 at the optic chiasm. First, the chiasm defects of mice lacking NrCAM (Williams et al., 2006; data not shown) versus VEGF164 and NRP1 appear distinct. Second, the temporal requirement for

NrCAM versus HDAC inhibitor VEGF164 and NRP1 in contralateral RGC axon guidance differs: defective midline crossing occurs in Nrp1 null and Vegfa120/120 mutants already at E14.0, when the first RGC axons extend through the chiasm ( Godement et al., 1987), while midline crossing in NrCAM null mutants is affected

only late in development, from E17.5 onward ( Williams et al., 2006). Finally, the retinal origin of the excess ipsilateral projections differs, as VEGF164 signaling through NRP1 promotes the contralateral projection of RGCs originating whatever throughout the retina, whereas NrCAM is essential for contralateral growth of a small subset of axons that originate exclusively in the ventrotemporal retina ( Williams et al., 2006). Based on these differences, we conclude that NRP1 and NrCAM function independently of each other to promote contralateral axon growth of RGC axons. In addition to promoting contralateral guidance of RGC axons, we found that VEGF164/NRP1 signaling promotes axon cohesion within the optic tracts. Thus, mutants lacking VEGF164 or NRP1 showed defasciculation of both the ipsilateral and contralateral tract. It is not known if VEGF164 acts as an extrinsic signal in the axonal environment to control fasciculation or, because it is also expressed by RGCs themselves, in a local autocrine fashion. Further in vivo studies, for example with tissue-specific NRP1 knockouts, will be necessary to fully understand this aspect of the phenotype. Interestingly, loss of Dicer, a protein essential for the maturation of regulatory micro RNAs that regulate Nrp1 among several other targets ( Zhou et al., 2008), leads to similar defasciculation and also increases the ipsilateral projection ( Pinter and Hindges, 2010).

Our finding that virtually all vesicles are release-competent is at odds with a recent study using photoconversion of FM1-43FX in acute hippocampal slices (Marra et al., 2012). With that method, a much smaller fraction of vesicles was found to be labeled (17%). When we assume that stimulation, dye loading, and photoconversion were all saturating, the easiest way to reconcile our data with the FM dye results is to assume that the majority of release events at mature hippocampal synapses are very brief or require the formation of a small fusion pore (Aravanis et al., 2003; Harata et al., 2006; Klingauf et al., 1998; Richards et al., 2005; Zhang et al., 2009). Both would allow the release of H+ and

glutamate but would effectively prevent full FM1-43 staining of the vesicle membrane.

Previous experiments GSK126 clinical trial have already suggested this to be the case (Harata et al., 2006; Zhang et al., 2009). Alternatively, could we have overestimated the recycling pool size by a factor of five? We consider an error of this magnitude unlikely, as we arrived at the same estimate using two calibration methods (NH4Cl, Nigericin/Monensin), and developing a ratiometric indicator allowed us to use both the same (Figure S4) or, more importantly, different sets of boutons for measurement and calibration. We found a dramatic acceleration of vesicle cycling kinetics at developing SC synapses, similar to changes reported during maturation of the calyx of Held. In this giant synapse, MK-2206 in vivo containing hundreds of active zones (AZs) (Sätzler et al., 2002), the maximum vesicle retrieval rate at a given stimulation intensity increases dramatically after hearing onset (immature calyx: 0.2 SVs

s−1 AZ−1; mature calyx: 7.2 SVs Thymidine kinase s−1 AZ−1 [Renden and von Gersdorff, 2007]) and the readily releasable vesicle pool becomes twice as large (Taschenberger and von Gersdorff, 2000). If we assume an average of ∼200 SV and a single AZ per SC bouton (Shepherd and Harris, 1998), our estimates of endocytosis from fluorescence decay measurements translate to retrieval rates of 0.9 SVs s−1 AZ−1 for immature and 5.7 SVs s−1 AZ−1 for mature boutons. It is striking that these synapses of very different size improve the performance of vesicle recycling during maturation in the same way, suggesting fundamental mechanisms that govern presynaptic development in intact tissue. Compared to mature synapses in tissue, retrieval rates that we (1.5 SVs s−1 AZ−1) and others (1 SVs s−1 AZ−1 [Sankaranarayanan and Ryan, 2000]) measured in dissociated culture were markedly lower, even though these cultures had been kept in the incubator for several weeks. It had been noted previously that both endocytic rate and resting pool size in dissociated cells are stable between the second and third week in vitro (Armbruster and Ryan, 2011; Fernandez-Alfonso and Ryan, 2008), even though spine synapse formation in this preparation peaks at this time (Papa et al., 1995).

Transient transfection was accomplished by using half of the manufacturer’s recommended amount of DNA (2 μg per 35 mm dish or 0.4 μg per 12 mm coverslip in 24-well dish) and Lipofectamine 2000 (5 μl per 35 mm

dish or 1 μl per 12 mm coverslip; Invitrogen, NY). Microelectrode recordings were performed in a perfused chamber with the bath temperature kept at 33°C–35°C by a temperature controller. The bath solution contained 150 mM NaCl, 4 mM KCl, 2 mM CaCl2, 1 mM MgCl2, 5 mM D-glucose, and 5 mM HEPES, pH 7.4. We used 3–5 MΩ glass patch pipettes (capillary tubing with 1.5/0.75 mm OD/ID-World Precision Instruments, FL) that were pulled on a P-97 Flaming/Brown type micropipette puller (Sutter Instrument Company, CA). The pipette solution contained 120 mM K-aspartate, 4 mM NaCl, 4 mM MgCl2, 1 mM check details CaCl2, 10 mM EGTA, 3 mM Na2ATP, and 5 mM HEPES, pH 7.2. Voltage-clamp recordings in the whole-cell IWR-1 in vitro configuration were performed using a Patch Clamp PC-505B amplifier (Warner Instruments, CT) with a holding potential of −70mV. Spontaneous activity of cultured hippocampal neurons

was recorded in current clamp mode without holding current injection. For stimulation experiments, action potentials were evoked by a 2 ms current injection. The pipette solution for neuron recordings contained 120 mM K-gluconate, 3 mM KCl, 7 mM NaCl, 4 mM Mg-ATP, 0.3 mM Na-GTP, 20 mM HEPES, and 14 mM Tris-phosphocreatin (pH adjusted with KOH to pH 7.3) (Popovic et al., 2011). Whole-cell patch-clamped cells were imaged either with a Nikon Eclipse E6000FN upright microscope with a water immersion objective, Nikon Rolziracetam Fluor 60×/1.00 N.A., or with a Nikon Eclipse TE300 inverted microscope with a 60×/1.40 N.A. oil immersion objective lens (Nikon, NY). For data collected with a 150 W Xenon arc lamp (Opti Quip, NY), we used two filter sets either an excitation filter HQ480/30X, a dichroic mirror 505DCXR and an emission filter HQ510LP (Chroma, Bellows Falls, VT) or GFP-3035B filter cube with an excitation filter 472/30 nm, dichroic mirror

495 nm, and emission filter 520/35 nm (Semrock, Rochester, NY). For data recorded with laser illumination, either a MLL-III-473 nm 50 mW or a MLL-FN-473 nm 50 mW (Changchun New Industries Optoelectronics Tech. Co., China) was used. The laser light was transmitted into the microscope by a multimode fiber coupler (Siskiyou, OR), a quartz light guide, and an Achromatic EPI-Fluorescence Condenser (Till Photonics, NY). For laser illumination, the excitation filter was removed from the filter cube. The fluorescence image was demagnified by an Optem zoom system, A45699 (Qioptiq LINOS Inc, NY), and projected onto the 80 × 80 pixel chip of a NeuroCCD-SM camera controlled by NeuroPlex software (RedShirtImaging, GA). The images were recorded at a frame rate of 1000 fps for HEK293 cells and at 2000 fps for neuron measurements. When we used laser excitation the recordings were from single trials.

, 2008 and Kaeser et al., 2011). The central PDZ-domain of RIMs binds at least two proteins: ELKS (Ohtsuka et al., 2002 and Wang et al., 2002) and N- and P/Q-type but not L-type Ca2+ channels (Kaeser et al., 2011). The physiological importance of ELKS binding to RIMs is unclear since the synaptic function of ELKS remains enigmatic (see below). In contrast, the binding of the RIM PDZ-domain to Ca2+ channels

is essential for recruiting Ca2+ channels to active zones (Kaeser et al., 2011 and Han et al., 2011). Synapses expressing mutant RIM that lacks the PDZ-domain exhibit Selleck MEK inhibitor a selective loss of presynaptic Ca2+ channels, with a resulting shift in the Ca2+-dependence of release to a higher Ca2+-requirement and a desynchronization of release (Kaeser et al., 2011). In addition to binding directly to RIMs, Ca2+ channels are tethered to the active zone by binding to RIM-BPs which in turn bind to RIMs (Figure 2). Specifically, the SH3-domains of RIM-BPs interact with proline-rich sequences of RIMs (localized between

this website their C2A and C2B domains) and of Ca2+ channels (in their cytoplasmic tails). A RIM fragment consisting of only its PDZ domain and proline-rich sequence is sufficient to rescue the presynaptic loss of Ca2+ channels in RIM-deficient synapses (Kaeser et al., 2011). Together, these data suggest that Ca2+ channels are recruited to active zones by a tripartite complex composed of RIMs, RIM-BPs, and the C-terminal tails of the channels (Figure 3). The function of the RIM C2 domains remains poorly

understood. The C2B domain binds to α-liprins and synaptotagmin-1 (Schoch et al., 2002), and the C2A domain may bind to SNARE proteins (Coppola et al., 2001), but it is unclear whether these interactions are physiologically relevant. The C2 domains may also bind to Ca2+ channels (Coppola et al., 2001), and the C2B domain of RIMs modulates Ca2+ channel opening (Uriu et al., 2010 and Kaeser et al., 2012). A fragment containing only the C2A and C2B domains of RIM partly rescues the decrease in synaptic strength observed in RIM-deficient synapses, without reversing the loss of presynaptic Ca2+ channels, suggesting that the C2 domains of RIM perform an active function in release (Kaeser et al., Edoxaban 2011). However, the nature of this function and its relation to the biochemical activities of the C2 domains remain unknown. RIM-BPs are large multidomain proteins (Figure 2). Vertebrates express three RIM-BP genes (Wang et al., 2000 and Mittelstaedt and Schoch, 2007), whereas Drosophila expresses only a single gene ( Liu et al., 2011). All RIM-BPs contain one central and two C-terminal SH3 domains and three central fibronectin III domains ( Wang et al., 2000 and Mittelstaedt and Schoch, 2007). The sequences separating these domains lack identifiable domains and vary among RIM-BP isoforms.

Interestingly, Pavlovian fear conditioning increased expression of both genes to similar levels in control and Tet1KO mice. However, extinction training resulted in significant induction of Npas4 and c-Fos expression in Tet1+/+

but not in Tet1KO mice ( Figure 5E). To assess whether any of three Tet genes are induced upon fear condition or extinction training, we measured Tet1/Tet2/Tet3 mRNA levels in hippocampi HDAC inhibitor of the same groups of animals and found that none of the Tets showed obvious induction ( Figure S4B). This study focuses on characterization of adult Tet1KO mice and details the consequences of Tet1 loss in the brain. We found that Tet1 ablation leads to downregulation of a group of neuronal activity-regulated genes Selleck SP600125 in cortex and hippocampus, alterations in synaptic plasticity, and specific cognitive impairment in memory extinction. We also show that the promoter region of a critical upstream factor regulating multiple neuronal activity-regulated genes, Npas4, is hypermethylated in Tet1KO mice. The proper control of the methylation status of Npas4 appears to be important for its expression

and for the regulation of its downstream targets, such as c-Fos, that are instrumental in mediating synaptic plasticity and cognition. Below, we will discuss the potential consequences of our findings and the questions out that remain to be answered. We should first reiterate that we did not observe any abnormalities in the overall health of Tet1KO mice. This finding is in line with our previous work (Dawlaty et al., 2011) that Tet1

is largely dispensable for embryonic and postnatal development. Our extensive examination of postnatal Tet1KO brains did not reveal any obvious abnormalities (Figure 1, Figure S1C, and data not shown) confirming that the loss of Tet1 does not affect embryonic neurogenesis, neuronal differentiation, and brain development. The absence of severe phenotypic abnormalities following total Tet1 ablation is likely due to the fact that this genetic manipulation did not result in a significant overall increase in 5mC content in the brain (Figure 1B). One obvious explanation for this is that Tet1/Tet2/Tet3 proteins play somewhat redundant roles in the maintenance of appropriate DNA methylation levels and conversion of 5mC to 5hmC in the brain and/or that their roles in normal cellular homeostasis are relatively subtle and cannot be discerned from the examinations performed here. A thorough examination of various behavioral parameters in Tet1KO mice demonstrated normal exploratory behavior, anxiety, and depression-related behaviors.

, 2008). Given the involvement of inhibition in all aspects of brain function, it is not surprising that changes in GABAergic signaling, and interneuron structure and function, have been reported in many pathological states, including schizophrenia (Lewis et al., 2012), autism (Chao et al., 2010; Pizzarelli and Cherubini, 2011), affective disorders (Brambilla et al., 2003; Möhler, 2012), and fragile X syndrome (Olmos-Serrano et al., 2010). Deficits in cognitive functions in Down syndrome have also been attributed in part to altered inhibition, and chronic partial blockade of GABAA receptors www.selleckchem.com/products/3-methyladenine.html with

picrotoxin at subconvulsant doses ameliorates some behavioral deficits in a mouse model (Fernandez et al., 2007). GABAA receptor plasticity has an important and potentially maladaptive role in status epilepticus, in which desensitization and internalization are thought to contribute to a progressive loss of effect of benzodiazepine anticonvulsants (Kapur and Coulter, 1995; selleck chemicals Kapur and Macdonald, 1997; Brooks-Kayal et al., 1998). In the longer term, several GABAA receptor subunits undergo changes in expression, and α5 subunits in particular undergo a robust downregulation (Houser and Esclapez, 2003). This subunit contributes to tonic inhibition at intermediate ambient GABA concentrations. Although a loss of tonic inhibition might be expected (and

to contribute to epileptogenesis after severe seizures), compensation by other subunits has been reported (Scimemi et al., 2005). Changes in subunits contributing to tonic inhibition,

as well as in progesterone metabolites acting on these subunits, also occur during the estrus cycle, possibly contributing to catamenial dysphoric symptoms and changes in susceptibility to seizures (Maguire et al., 2005). Several other forms of plasticity of inhibition in epilepsy have been reviewed by Fritschy (2008). Altered inhibition has also been reported in other disorders including pain sensitization (Sivilotti and Woolf, 1994) and opiod addiction (Nugent et al., 2007). In many of these disorders, however, it is difficult to disentangle a pathogenic role of the primary alteration in inhibition from a compensatory PD184352 (CI-1040) effect. Despite the absence of an obvious local coincidence detector at GABAergic synapses, abundant forms of inhibitory plasticity have emerged. The computational roles of these phenomena are likely to go far beyond mere stabilization of brain excitability. Indeed, the psychotropic effects of recreational CB1 agonists hint that modifying GABAergic signaling has extensive consequences for many cognitive and vegetative functions. Whether and how the numerous forms of inhibitory plasticity can be harnessed for therapeutic purposes represents a challenge for further work.

An index of 0 was attributed to the cultures showing no preferential growth. We prepared 20 μm cryosections covering the entire spinal cord from embryos fixed in 4% paraformaldehyde, embedded in 7.5% gelatin, 15% sucrose in PBS, and incubated over night at 4°C with the following antibodies: Plexin-A1 (1/100, AbCAM), Neurofilament 160 kDa (1/100, RMO Zymed), Ngn1 (1/100, Santa-Cruz), Robo3 (1/100, R&D), DCC (1/100, BD), GFRα1 (1/100, R&D), PSA-NCAM (1/100, DSHB), and secondary antibodies Alexa 594, Alexa 488 (1/500, Invitrogen), and Fluoroprobe 546 (1/100) with bisbenzimide (1/2,000, Promega). For lacZ

staining, spinal cord open books were Androgen Receptor Antagonist prepared, fixed in 4% PFA, and incubated with 5 mM Ferro/Ferri cyanide, 2 mM MgCl2, and

1 mg/ml X-Gal in PBS at 37°C and the reaction was stopped in PBS. Chromogenic immunostaining and in situ hybridization was performed as described in Moret et al. (2007). Nuclei were stained with bisbenzimide (Promega) and actin with TRITC-phalloidin in neuronal cultures. Spinal cords were dissected from E12.5 and E13.5 embryos of the gdnf NrCAM, NrCAM/gdnf, NCAM, and RET-wnt-flox Ibrutinib mouse lines and prepared in an “open book” conformation and fixed in 4% PFA overnight. Small crystals of DiI (Invitrogen) were inserted in the dorsal part of one hemicord. Axon trajectories were observed using fluorescence microscopy after 48 hr. Isolated dorsal spinal cord fresh tissue was incubated for 1 hr at 37°C with control, FPcm, or gdnf and treated according to manufacturer’s instructions (Calbiochem). Calpain activity was measured by fluorogenic activity (Victor 3 multilabel counter, Perkin Elmer). For t-BOC assays, dorsal spinal over cord tissues from E12.5 embryos were dissociated, and cells were plated into polylysin- and laminin-coated glass coverslips in Neurobasal medium (GIBCO) supplemented with B27 (GIBCO), glutamine (GIBCO), and Netrin-1 (R&D) medium.

After 2 days in culture, neurons were incubated with control, FPcm, or gdnf for 1 hr at 37°C. Neurons were then treated with t-BOC (10 μM; Invitrogen) for 30 min at 37°C; staining was observed immediately over 20 min maximum. For the analysis, images from all conditions were collected with the same settings. Using ImageJ, a constant threshold was applied to all images to collect the high t-BOC cell population over the whole population, which was quantified in phase contrast. To measure Plexin-A1 levels, we treated neuronal cultures with control, FPcm, or gdnf and processed for immunohistochemistry with anti-Plexin-A1 antibody and phalloidin. Images of individual neurons were taken and the Plexin-A1 fluorescence was quantified using ImageJ software. To measure Plexin-A1 levels in vivo, transverse sections were performed and processed for immunohistochemistry with anti-Plexin-A1 and anti-Nf160kD antibodies. The fluorescence was quantified using ImageJ software into the FP and the two adjacent PC domains and normalized to the selected area.

In support of this, proximal centrosome localization was sometimes unstable, and the centrosome could reorient during Stage 3. This was especially obvious in cases where the bead became dislodged from its original position after neurite contact and was pulled onto the surface of the cell body. The neurite that had originally contacted the bead remained committed to form the axon, while the centrosome tracked

the bead as it moved around the cell body. This indicates that Laminin-dependent axon commitment selleckchem is an early event that only transiently depends on localized Laminin contact, and is separable from the persistent effect of Laminin on centrosome localization. Although we have established that Lam1 is sufficient to direct axon commitment in vitro, we wanted to know if this was also the case in vivo. To answer this question we developed a system to implant polystyrene beads into the retina of 24 hpf zebrafish embryos using a sharp glass needle. This system allowed us to reintroduce Lam1 into a Lamα1-deficient embryo, to unambiguously identify where the ectopic Lam1 was located, and to assess its influence on polarizing RGCs. The bead implantation procedure did not have a dramatic effect on the structure of Ibrutinib nmr the retina, which had no noticeable structural defects, and appeared normal with a bead, or a clump of beads, suspended within it (data

not shown). Lam1-coated beads were implanted into 24–28 hpf lamα1 morphant embryos ( Figure 6A). Embryos were grown until 3 dpf, and we imaged

them by confocal microscopy to look for an interaction between the beads and RGC axons. In many cases an interaction between the beads and RGC axons was obvious, where large axon bundles were observed in contact with the beads/bead clumps. Axons hugged the surface of the beads, often causing them to lie within the axon fascicle ( Figure 6B). Beads were generally positioned at the base of the RGC axon bundles, close to RGC cell bodies, consistent Oxalosuccinic acid with the hypothesis that Lam1 is acting to direct polarization and RGC axon sprouting. Axon growth can be directed by the physical nature of a substrate. Therefore, it is possible that the physical presence of a polystyrene bead, rather than the Lam1 coating, is able to influence RGC polarization and axon extension. To control for this possibility, we implanted BSA-coated beads into Lamα1 morphant embryos. BSA-coated beads very rarely showed an association with RGC axons. To quantify this observation, confocal stacks from retinas implanted with either Lam1 or BSA-coated beads were blinded and classified as either showing a clear and dramatic interaction with RGC axons, where many RGC axons were seen in contact with the surface of the bead (similar to those shown in Figure 6B), or not.

These results indicate that a fatigued athlete may have to increase the elongation

to absorb a given amount of energy and thus increased muscle strains in the movement and the risk for muscle strain injury. The study by Small et al.72 also provides support for fatigue as being a risk factor. They found that fatigue significantly increased the knee flexion angle at which peak knee eccentric flexion torque occurred. This result combined with the results of those Idelalisib solubility dmso studies on the general mechanism of muscle strain injury and optimum hamstring muscle length indicate that hamstring muscle strain may be increased in a given movement when fatigued. To a certain degree, this result also supports increasing hamstring flexibility as a prevention strategy for hamstring strain injury. Hamstring strain injury may be associated with low back pain in the zygapophyseal origin area.73 Mooney and Robertson74 found increased electrical activities and decreased flexibility of hamstring muscles for patients with low back pain. These results indicate that low back pain may provoke hamstring responses such as increased tension and result in muscle damage.73 In a retrospective study, Hennessey and Watson75 found a significant increase of lumbar lordosis among hamstring injured athletes in comparison buy AZD6244 to their

uninjured counterparts, which indicates a possible association between hamstring strain injury and lumbar posture. However, a study by Verrall et al.2 found that a past history of back injury did correlate with an increased risk of posterior thigh pain, which did not necessarily mean a hamstring strain injury. Abnormal neural tension was another proposed modifiable risk factor for the recurrence of hamstring strain injuries.76 Abnormal neural tension is defined as abnormal physiological and mechanical responses in the neuromuscular system when the normal range of movement and stretch capabilities no is exceeded.77 and 78

Neural tension can be evaluated using the Slump test.77 and 78 Branches of the sciatic nerve can be tethered to the scar after a hamstring injury, and create increased neural tension with or without local irritation, which may result in local damage to the hamstring muscle.73 Turl and George76 reported that more than 50% of athletes had abnormal neural tension after non-repetitive grade I hamstring strain injuries. However, as previous studies on the mechanism of muscle strain injury demonstrated, muscle strain injuries are caused by strain, not by force.35 and 36 As the relationship between muscle strain injury and abnormal neural tension is still speculative in nature, the relevance of incorporating special mobility techniques including “neural tension positions” in rehabilitation programs has not yet been scientifically established.