Emergence of functional sensory subtypes as defined by transient receptor potential channel expression

The existence of heterogeneous populations of dorsal root ganglion (DRG) neurons conveying different somatosensory information is the basis for the perception of touch, temperature, and pain. A differential expression of transient receptor potential (TRP) cation channels contributes to this functional heterogeneity. However, little is known about the development of functionally diverse neuronal subpopulations. Here, we use calcium imaging of acutely dissociated mouse sensory neurons and quantitative reverse transcription PCR to show that TRP cation channels emerge in waves, with the diversification of functional groups starting at embryonic day 12.5 (E12.5) and extending well into the postnatal life. Functional responses of voltage-gated calcium channels were present in DRG neurons at E11.5 and reached adult levels by E14.5. Responses to capsaicin, menthol, and cinnamaldehyde were first seen at E12.5, E16.5, and postnatal day 0 (P0), when the mRNA for TRP cation channel, subfamily V, member 1 (TRPV1), TRP cation channel, subfamily M, member 8 (TRPM8), and TRP cation channel, subfamily A, member 1 (TRPA1), respectively, was first detected. Cold-sensitive neurons were present before the expression or functional responses of TRPM8 or TRPA1. Our data support a lineage relationship in which TRPM8- and TRPA1-expressing sensory neurons derive from the population of TRPV1-expressing neurons. The TRPA1 subpopulation of neurons emerges independently in two distinct classes of nociceptors: around birth in the peptidergic population and after P14 in the nonpeptidergic class. This indicates that neurons with similar receptive properties can be generated in different sublineages at different developmental stages. This study describes for the first time the emergence of functional subtypes of sensory neurons, providing new insight into the development of nociception and thermoreception

The boundary cap: a source of neural crest stem cells that generate multiple sensory neuron subtypes

The boundary cap (BC) is a transient neural crest-derived group of cells located at the dorsal root entry zone (DREZ) that have been shown to differentiate into sensory neurons and glia in vivo. We find that when placed in culture, BC cells self-renew, show multipotency in clonal cultures and express neural crest stem cell (NCSCs) markers. Unlike sciatic nerve NCSCs, the BC-NCSC (bNCSCs) generates sensory neurons upon differentiation. The bNCSCs constitute a common source of cells for functionally diverse types of neurons, as a single bNCSC can give rise to several types of nociceptive and thermoreceptive sensory neurons. Our data suggests that BC cells comprise a source of multipotent sensory specified stem cells that persist throughout embryogenesis

Collaborative platforms for streamlining workflows in Open Science

Despite the internet’s dynamic and collaborative nature, scientists continue to produce grant proposals, lab notebooks, data files, conclusions etc. that stay in static formats or are not published online and therefore not always easily accessible to the interested public. Because of limited adoption of tools that seamlessly integrate all aspects of a research project (conception, data generation, data evaluation, peer-reviewing and publishing of conclusions), much effort is later spent on reproducing or reformatting individual entities before they can be repurposed independently or as parts of articles.

We propose that workflows - performed both individually and collaboratively - could potentially become more efficient if all steps of the research cycle were coherently represented online and the underlying data were formatted, annotated and licensed for reuse. Such a system would accelerate the process of taking projects from conception to publication stages and allow for continuous updating of the data sets and their interpretation as well as their integration into other independent projects.

A major advantage of such workflows is the increased transparency, both with respect to the scientific process as to the contribution of each participant. The latter point is important from a perspective of motivation, as it enables the allocation of reputation, which creates incentives for scientists to contribute to projects. Such workflow platforms offering possibilities to fine-tune the accessibility of their content could gradually pave the path from the current static mode of research presentation into
a more coherent practice of open science

Short-interval intracortical inhibition: Comparison between conventional and threshold-tracking techniques

BACKGROUND: Short-interval intracortical inhibition (SICI) is conventionally measured as the relative amplitude reduction of motor evoked potentials (MEPs) by subthreshold conditioning stimuli. In threshold-tracking SICI (T-SICI), stimulus intensity is instead adjusted repeatedly to maintain a constant MEP and inhibition is measured as the relative threshold increase. T-SICI is emerging as a useful diagnostic test, but its relationship to conventional amplitude SICI (A-SICI) is unclear. OBJECTIVE: To compare T-SICI and its reliability with conventional A-SICI measurements. METHODS: In twelve healthy volunteers (6 men, median age 30 years), conventional and T-SICI were recorded at conditioning stimuli (CS) of 50-80% resting motor threshold (RMT) and interstimulus interval of 2.5 ms. Measurements were repeated on the same day and at least a week later by a single operator. RESULTS: Across the CS range, mean group T-SICI showed a strong linear relationship to the mean group values measured by conventional technique (y = 29.7-0.3x, R2 = 0.99), but there was considerable interindividual variability. At CS 60-80% RMT, T-SICI had excellent intraday (intraclass correlation coefficient, ICC, 0.81-0.92) and adequate-to-excellent interday (ICC 0.61-0.88) reproducibility. Conventional SICI took longer to complete (median of 5.8 vs 3.8 min, p < 0.001) and tended to have poorer reproducibility (ICC 0.17-0.42 intraday, 0.37-0.51 interday). With T-SICI, smaller sample sizes were calculated for equally powered interventional studies. CONCLUSION: The close relationship between conventional and T-SICI suggests that both techniques reflect similar cortical inhibitory mechanisms. Threshold-tracking measurements of SICI may be able to improve reproducibility, to shorten acquisition time and to reduce sample sizes for interventional studies compared with the conventional technique

Long-term outcome of brachial plexus re-implantation after complete brachial plexus avulsion injury.

BACKGROUND: Complete brachial plexus avulsion injury is a severe disabling injury due to traction to the brachial plexus. Brachial plexus re-implantation is an emerging surgical technique for the management of complete brachial plexus avulsion injury. OBJECTIVE: We assessed the functional recovery in 15 patients who have undergone brachial plexus re-implantation surgery after complete brachial plexus avulsion injury with clinical examination and electrophysiological testing METHODS: We included all patients that underwent brachial plexus re-implantation in our institution between 1997 and 2010. Patients were assessed with detailed motor and sensory clinical examination and motor and sensory electrophysiological tests. RESULTS: We found that patients who had re-implantation surgery demonstrated an improvement in MRC power in the deltoid, pectoralis and infraspinatous muscles and "global MRC score". Eight patients achieved at least grade 3 MRC power in at least one muscle group of the arm. Improved re-innervation by EMG criteria was found in infraspinatous, biceps and triceps muscles. There was evidence of ongoing innervation in three patients. Sensory testing in affected dermatomes also showed better recovery at C5, C6 and T1 dermatomes. The best recovery was seen in the C5 dermatome. CONCLUSION: Our results demonstrate a definite but limited improvement in motor and sensory recovery following re-implantation surgery in patients with complete brachial plexus injury. We hypothesize that further improvement may be achieved by using regenerative cell technologies at the time of repair

Heparin and air filters reduce embolic events caused by intra-arterial cerebral angiography - A prospective, randomized trial

Background-Intra-arterial cerebral angiography is associated with a low risk for neurological complications, but clinically silent ischemic events after angiography have been seen in a substantial number of patients.Methods and Results-In a prospective study, diffusion-weighted magnetic resonance imaging (DW-MRI) before and after intra-arterial cerebral angiography and transcranial Doppler sonography during angiography were used to evaluate the frequency of cerebral embolism. One hundred fifty diagnostic cerebral angiographies were randomized into 50 procedures, each using conventional angiographic technique, or systemic heparin treatment throughout the procedure, or air filters between the catheter and both the contrast medium syringe and the catheter flushing. There was no neurological complication during or after angiography. Overall, DW-MRI revealed 26 new ischemic lesions in 17 patients (11%). In the control group, 11 patients showed a total of 18 lesions. In the heparin group, 3 patients showed a total of 4 lesions. In the air filter group, 3 patients exhibited a total of 4 lesions. The reduced incidence of ischemic events in the heparin and air filter groups compared with the control group was significantly different (P=0.002). Transcranial Doppler sonography demonstrated a large number of microembolic signals that was significantly lower in the air filter group compared with the heparin and control groups (P=0.01), which did not differ from each other.Conclusions-Air filters and heparin both reduce the incidence of silent ischemic events detected by DW-MRI after intra-arterial cerebral angiography and can potentially lower clinically overt ischemic complications. This may apply to any intra-arterial angiographic procedure

Wikis in scholarly publishing

Scientific research is a process concerned with the creation, collective accumulation, contextualization, updating and maintenance of knowledge. Wikis provide an environment that allows to collectively accumulate, contextualize, update and maintain knowledge in a coherent and transparent fashion. Here, we examine the potential of wikis as platforms for scholarly publishing. In the hope to stimulate further discussion, the article itself was drafted on &#x22;Species-ID&#x22;:http://species-id.net/w/index.php?title=Wikis_in_scholarly_publishing&#x26;oldid=3815 - a wiki that hosts a prototype for wiki-based scholarly publishing - where it can be updated, expanded or otherwise improved

Conventional and threshold-tracking transcranial magnetic stimulation tests for single-handed operation

Most single-pulse transcranial magnetic stimulation (TMS) parameters (e.g., motor threshold, stimulus-response function, cortical silent period) are used to examine corticospinal excitability. Paired-pulse TMS paradigms (e.g., short-and long-interval intracortical inhibition (SICI/LICI), short-interval intracortical facilitation (SICF), and short-and long-latency afferent inhibition (SAI/LAI)) provide information about intracortical inhibitory and facilitatory networks. This has long been done by the conventional TMS method of measuring changes in the size of the motor-evoked potentials (MEPs) in response to stimuli of constant intensity. An alternative threshold-tracking approach has recently been introduced whereby the stimulus intensity for a target amplitude is tracked. The diagnostic utility of threshold-tracking SICI in amyotrophic lateral sclerosis (ALS) has been shown in previous studies. However, threshold-tracking TMS has only been used in a few centers, in part due to the lack of readily available software but also perhaps due to uncertainty over its relationship to conventional single-and paired-pulse TMS measurements. A menu-driven suite of semi-automatic programs has been developed to facilitate the broader use of threshold-tracking TMS techniques and to enable direct comparisons with conventional amplitude measurements. These have been designed to control three types of magnetic stimulators and allow recording by a single operator of the common single-and paired-pulse TMS protocols. This paper shows how to record a number of single-and paired-pulse TMS protocols on healthy subjects and analyze the recordings. These TMS protocols are fast and easy to perform and can provide useful biomarkers in different neurological disorders, particularly neurodegenerative diseases such as ALS

Short interval intracortical inhibition: Variability of amplitude and threshold-tracking measurements with 6 or 10 stimuli per point

Reduced short-interval intracortical inhibition (SICI) in motor neuron disease has been demonstrated by amplitude changes (A-SICI) and threshold-tracking (T-SICI) using 10 stimuli per inter-stimulus interval (ISI). To test whether fewer stimuli would suffice, A-SICI and T-SICI were recorded twice from 30 healthy subjects using 6 and 10 stimuli per ISI. Using fewer stimuli increased mean A-SICI variances by 23.8% but the 7.3% increase in T-SICI variance was not significant. We conclude that our new parallel threshold-tracking SICI protocol, with 6 stimuli per ISI, can reduce time and stimulus numbers by 40% without appreciable loss of accuracy

Potential risks of iatrogenic complications of nerve conduction studies (NCS) and electromyography (EMG)

AbstractNerve conduction and electromyography studies are generally well tolerated and pose little risk to patients of serious adverse events in the hands of a well-trained competent practitioner. However, some patients and certain examinations do carry a higher risk of potential complications. It is good medical practice to inform patients of any risks, their potential severity and relative frequency. In order to obtain informed consent a dialogue should take place about the nature, purpose and effects of the studies, so patients can decide if they wish to undergo the proposed investigation. In this educational review we identify those procedures and patients at risk, and provide pragmatic practice recommendations for managing these material risks