Neonatal Mice Spinal Cord Interneurons Sending Axons in Dorsal Roots

Background: Spinal cord interneurons send their axons in the dorsal root. Their antidromic fire could modulate peripheral receptors. Thus, it could control pain, other sensorial modality, or muscle spindle activity. In this study, we assessed a staining technique to analyze whether interneurons send axons in the neonate mouse’s dorsal roots. We conducted experiments in 10 Swiss-Webster mice, which ranged in age from 2 to 13 postnatal days. We dissected the spinal cord and studied it in vitro. Results: We observed interneurons in the spinal cord dorsal horn sending axons through dorsal roots. A mix of fluorochromes applied in dorsal roots marked these interneurons. They have a different morphology than motoneurons. Primary afferent depolarization in afferent terminals produces antidromic action potentials (dorsal root reflex; DRR). These reflexes appeared by stimulation of adjacent dorsal roots. We found that in the presence of bicuculline, DRR recorded in the L4 dorsal root evoked by L5 dorsal root stimulation was reduced. Simultaneously, the monosynaptic reflex (MR) in the L5 ventral root was not affected; nevertheless, a long-lasting after discharge appeared. The addition of 2-amino-5 phosphonovalric acid (AP5), an antagonist of NMDA receptors, abolished the MR without changing the after discharge. Action potentials persisted in dorsal roots even in low Ca2+ concentration. Conclusions: Thus, firing interneurons could send their axons by dorsal roots. Antidromic potentials may be characteristics of the neonatal mouse, probably disappearing in adulthood.

Fatigue-induced modulation of human soleus H-reflex in conditions of pair tibial nerve stimulation in untrained and trained people

Monosynaptic reflex indices peculiarities, concerned with adaptative reactions to the long-term physical exercise, might add new data about mechanisms of human nervous system plasticity. The objective of the research was to investigate the influence of fatigue on human soleus H (Hoffmann) reflex in conditions of pair stimulation of tibial nerve with inter stimulus interval 500 m sin tenun trained people (age: M = 25,3, SE = 1,6 years) and ten trained athletes (age: M = 20,5, SE = 0,5 years). H-reflex study was performed using neurodiagnostic complex Nicolet Biomedical Viking Select (Viasys Health care, USA) at rest: before and after long-lasting isometric voluntary contraction of calf muscle, which caused the soleus muscle fatigue; the muscle force was equal to 75 % of maximal voluntary contraction. Test and conditioned responses (by means of stimulation with first and second impulses from pair) were registered. Homosynaptic postactivation depression (HPAD), associated with pair stimulation of tibial nerve, led to 56 % and 51 % inhibition of H-reflex in untrained and trained people at rest, respectively (p < 0,05). After fatiguing voluntary contraction the amplitudes of test and conditioned soleus H-reflex were both reduced approximately in half. Then both H-reflex amplitudes subsequently recovered, more rapidly in trained people. Soleus H-reflex inhibition might be due to the activation of the groups III and IV afferent nerves under the influence of mechanical and metabolic changes in the muscle. It was also found that HPAD H-reflex inhibition intensity increased by 20 % in untrained people and by 15 % in trained ones at 90 s after fatiguing voluntary contraction (p < 0,05). It is assumed that complex influence of fatigue and homosynaptic postactivation depression was more pronounced in untrained people in comparison with trained ones. It can be ascribed to athletes adaptation to the long-term physical exercise.

Task-dependent modulation of spinal and transcortical stretch reflexes linked to motor learning rate

It is generally believed that task-dependent control of body configuration (‘posture’) is achieved by adjusting voluntary motor activity and transcortical ‘long-latency’ reflexes. Spinal monosynaptic circuits are thought not to be engaged in such task-level control. Similarly, being in a state of motor learning has been strongly associated only with an upregulation of feedback responses at transcortical latencies and beyond. In two separate experiments, the current study examined the task-dependent modulation of stretch reflexes by perturbing the hand of human subjects while they were waiting for a ‘Go’ signal to move at the different stages of a classic kinematic learning task (visuomotor rotation). Although the subjects had to resist all haptic perturbations equally, the study leveraged that task-dependent feedback controllers may already be ’loaded’ at the movement anticipation stage. In addition to an upregulation of short- and long-latency reflex gains during early exposure to the visual distortion, I found a relative inhibition of reflex responses in the ‘washout’ stage (sensory realignment state). For more distal muscles (brachioradialis), this inhibition also extended to the monosynaptic reflex response (‘R1’). These R1 gains reflected individual motor learning performance in the visuomotor task. The results demonstrate that the system’s ‘control policy’ in visuomotor adaptation can also include inhibition of proprioceptive reflexes, and that aspects of this policy can affect monosynaptic spinal circuits. The latter finding suggests a novel form of state-related control, probably realized by independent control of fusimotor neurons, through which segmental circuits can tune to higher-level features of a sensorimotor task.Additional InformationConflict of interestThe author declares no conflict of interest.Author contributionsM.D. devised, designed and implemented the project, analyzed the data and wrote the manuscript. The author approves the final version of the manuscript and is fully accountable for all aspects of the work. The experiments were performed at the Department of Integrative Medical Biology, Umeå University, Sweden.FundingThis work was financially supported through grants awarded to M.D. by the Kempe Foundation, the local Foundation for Medical Research (“Insamlingsstiftelsen”) and the Swedish Research Council (project 2016-02237).

A randomised controlled cross-over double-blind pilot study protocol on THC:CBD oromucosal spray efficacy as an add-on therapy for post-stroke spasticity

IntroductionStroke is the most disabling neurological disorder and often causes spasticity. Transmucosal cannabinoids (tetrahydrocannabinol and cannabidiol (THC:CBD), Sativex) is currently available to treat spasticity-associated symptoms in patients with multiple sclerosis. Cannabinoids are being considered useful also in the treatment of pain, nausea and epilepsy, but may bear and increased risk for cardiovascular events. Spasticity is often assessed with subjective and clinical rating scales, which are unable to measure the increased excitability of the monosynaptic reflex, considered the hallmark of spasticity. The neurophysiological assessment of the stretch reflex provides a precise and objective method to measure spasticity. We propose a novel study to understand if Sativex could be useful in reducing spasticity in stroke survivors and investigating tolerability and safety by accurate cardiovascular monitoring.Methods and analysisWe will recruit 50 patients with spasticity following stroke to take THC:CBD in a double-blind placebo-controlled cross-over study. Spasticity will be assessed with a numeric rating scale for spasticity, the modified Ashworth scale and with the electromyographical recording of the stretch reflex. The cardiovascular risk will be assessed prior to inclusion. Blood pressure, heart rate, number of daily spasms, bladder function, sleep disruption and adverse events will be monitored throughout the study. A mixed-model analysis of variance will be used to compare the stretch reflex amplitude between the time points; semiquantitative measures will be compared using the Mann-Whitney test (THC:CBD vs placebo) and Wilcoxon test (baseline vs treatment).Ethics and disseminationThe study was registered on the EudraCT database with number 2016-001034-10 and approved by both the Italian Medicines Agency (Agenzia Italiana del Farmaco) and local Ethics Committee ‘Comitato Etico Regionale della Liguria’. Data will be made anonymous and uploaded to a open access repository. Results will be disseminated by presentations at national and international conferences and by publication in journals of clinical neuroscience and neurology.