PRC1 sustains the integrity of neural fate in the absence of PRC2 function

Polycomb repressive complexes (PRCs) 1 and 2 maintain stable cellular memories of early fate decisions by establishing heritable patterns of gene repression. PRCs repress transcription through histone modifications and chromatin compaction, but their roles in neuronal subtype diversification are poorly defined. We found that PRC1 is essential for the specification of segmentally-restricted spinal motor neuron (MN) subtypes, while PRC2 activity is dispensable to maintain MN positional identities during terminal differentiation. Mutation of the core PRC1 component Ring1 in mice leads to increased chromatin accessibility and ectopic expression of a broad variety of fates determinants, including Hox transcription factors, while neuronal class-specific features are maintained. Loss of MN subtype identities in Ring1 mutants is due to the suppression of Hox-dependent specification programs by derepressed Hox13 paralogs (Hoxa13, Hoxb13, Hoxc13, Hoxd13). These results indicate that PRC1 can function in the absence of de novo PRC2-dependent histone methylation to maintain chromatin topology and postmitotic neuronal fate.

Characterization of Spinal Sensorimotor Network Using Transcutaneous Spinal Stimulation during Voluntary Movement Preparation and Performance

Transcutaneous electrical spinal stimulation (TSS) can be used to selectively activate motor pools based on their anatomical arrangements in the lumbosacral enlargement. These spatial patterns of spinal motor activation may have important clinical implications, especially when there is a need to target specific muscle groups. However, our understanding of the net effects and interplay between the motor pools projecting to agonist and antagonist muscles during the preparation and performance of voluntary movements is still limited. The present study was designed to systematically investigate and differentiate the multi-segmental convergence of supraspinal inputs on the lumbosacral neural network before and during the execution of voluntary leg movements in neurologically intact participants. During the experiments, participants (N = 13) performed isometric (1) knee flexion and (2) extension, as well as (3) plantarflexion and (4) dorsiflexion. TSS consisting of a pair pulse with 50 ms interstimulus interval was delivered over the T12-L1 vertebrae during the muscle contractions, as well as within 50 to 250 ms following the auditory or tactile stimuli, to characterize the temporal profiles of net spinal motor output during movement preparation. Facilitation of evoked motor potentials in the ipsilateral agonists and contralateral antagonists emerged as early as 50 ms following the cue and increased prior to movement onset. These results suggest that the descending drive modulates the activity of the inter-neuronal circuitry within spinal sensorimotor networks in specific, functionally relevant spatiotemporal patterns, which has a direct implication for the characterization of the state of those networks in individuals with neurological conditions.

Thenar Muscle Motor Imagery Increases Spinal Motor Neuron Excitability of the Abductor Digiti Minimi Muscle

When a person attempts intended finger movements, unintended finger movement also occur, a phenomenon called “enslaving”. Given that motor imagery (MI) and motor execution (ME) share a common neural foundation, we hypothesized that the enslaving effect on the spinal motor neuron excitability occurs during MI. To investigate this hypothesis, electromyography (EMG) and F-wave analysis were conducted in 11 healthy male volunteers. Initially, the EMG activity of the left abductor digiti minimi (ADM) muscle during isometric opposition pinch movement by the left thumb and index finger at 50% maximal effort was compared with EMG activity during the Rest condition. Next, the F-wave and background EMG recordings were performed under the Rest condition, followed by the MI condition. Specifically, in the Rest condition, subjects maintained relaxation. In the MI condition, they imagined isometric left thenar muscle activity at 50% maximal voluntary contraction (MVC). During ME, ADM muscle activity was confirmed. During the MI condition, both F-wave persistence and the F-wave/M-wave amplitude ratio obtained from the ADM muscle were significantly increased compared with that obtained during the Rest condition. No difference was observed in the background EMG between the Rest and MI conditions. These results suggest that MI of isometric intended finger muscle activity at 50% MVC facilitates spinal motor neuron excitability corresponding to unintended finger muscle. Furthermore, MI may induce similar modulation of spinal motor neuron excitability as actual movement.

Can Hybrid Synapse be Formed between Rat Spinal Motor Neurons and Major Pelvic Ganglion Neurons in vitro?

The purpose of this study is to determine whether synapses can be formed between spinal motor neurons (SMNs) and major pelvic ganglion (MPG) neurons of a rat in vitro. The green fluorescent protein (GFP)-labelled MPG cells were cultured together with SMNs in a specific medium. The synaptic-like contacts established between SMNs and MPG neurons were studied in co-cultures using morphologic and immunocytochemistry approaches. Phase-contrast observation of co-cultures showed apparent SMNs-MPG neurons contacts as early as three or four days in vitro. We demonstrate some evidence of synaptic contacts between SMNs and MPG neurons in vitro by immunostaining with antibody directed against postsynaptic density protein 95 (PSD-95). We describe the development process of a defined SMNs-MPG neurons co-culture system. The results suggest that the hybrid synapse formation that may occur between SMNs and MPG neurons in vitro played an essential role in the mechanisms of a regenerated bladder with an artificial somatic-autonomic reflex arc.

Involvement of RIG-I Pathway in Neurotropic Virus-Induced Acute Flaccid Paralysis and Subsequent Spinal Motor Neuron Death

Neurotropic viral infections are an increasingly common cause of immediate or delayed neuropsychiatric sequelae, cognitive impairment, and movement disorders or, in severe cases, death. Given the highest reported disability-adjusted life years and mortality rate worldwide, a better understanding of molecular mechanisms for underlying clinical manifestations like AFP will help in development of more effective tools for therapeutic solutions.

The manipulation of spinal motor neuron axonal growth promotes spinal cord repair

The loss of motor function in patients with spinal cord injury (SCI) is primarily due to the severing of the corticospinal tract (CST). Spinal motor neurons are located in the anterior horn of the spinal cord, and as the lower neurons of the CST, they control voluntary movement. Furthermore, its intrinsic axonal growth ability is significantly stronger than that of cerebral cortex pyramid neurons, which are the upper CST neurons. Therefore, we established an axonal regeneration model of spinal motor neurons to investigate the feasibility of repairing SCI by promoting axonal regeneration of spinal motor neurons. We demonstrated that conditionally knocking out pten in mature spinal motor neurons drastically enhanced axonal regeneration in vivo, and the regenerating axons of the spinal motor neurons re-established synapses with other cells in the damaged spinal cord. Thus, this strategy may serve as a novel and effective treatment method for SCI.

A Brainstem reticulotegmental neural ensemble drives acoustic startle reflexes

The reticulotegmental nucleus (RtTg) has long been recognized as a crucial component of brainstem reticular formation (RF). However, the function of RtTg and its related circuits remain elusive. Here, we report a role of the RtTg in startle reflex, a highly conserved innate defensive behaviour. Optogenetic activation of RtTg neurons evokes robust startle responses in mice. The glutamatergic neurons in the RtTg are significantly activated during acoustic startle reflexes (ASR). Chemogenetic inhibition of the RtTg glutamatergic neurons decreases the ASR amplitudes. Viral tracing reveals an ASR neural circuit that the cochlear nucleus carrying auditory information sends direct excitatory innervations to the RtTg glutamatergic neurons, which in turn project to spinal motor neurons. Together, our findings describe a functional role of RtTg and its related neural circuit in startle reflexes, and demonstrate how the RF connects auditory system with motor functions.

INFLUENCE OF THE SAGITTAL LUMBAR PARAMETERS ON THE STRESS-STRAIN STATE OF THE SPINAL MOTOR SEGMENTS AT TRANSPEDICULAR FIXATION

Objective. To study the stress-strain state of the elements of the human lumbar spine when we use the transpedicular system, taking into account different angular values of segmental and total lumbar lordosis. Methods. For computer modeling of the stress-strain state of the elements of the human lumbar spine after mono- and polysegmental fixation, the Workbench product was used, and for the construction of parametric three-dimensional geometricmodels — the SolidWorks computer-aided design system was used. 4 groups of decisions were studied, which differed in angular values of segmental and total lumbar lordosis. In each group, 11 models were analyzed that describe the lumbar segments after mono- and polysegmental fixation in various configurations of the sagittal alignment of the lumbar spine. Results. It was found that the maximum stress on the cortical bone is concentrated on the base of the LV in case of the «pathological» intervertebral disc LV–S in the group of patients with hyperlordosis. At polysegmental fixation of the LI – S, there is a redistribution of stress on the cortical bone of all vertebrae, the maximum values of which is present in the bodies of the LV and S vertebrae. And only in the group with hypolordosis this stress is minimal. The maximum stress was always on the overlying intervertebral disc during transpedicularfixation. Significant increasing of cartilage stress in the facet joints of the LIV–LV segment was recorded during fixation of the LV–S segmentin case of hyperlordosis. The maximum stress on the rods was identified in the group of patients with hyperlordosis and polysegmentalfixation of the LI –S, on screws — on LV, LIV, LIII vertebrae during fixation in all groups, except for hypolordosis. Conclusions. Increasing in angular values (hyperlordosis), which describe segmental and total lumbar lordosis, leads to the stress elevation in the fixing elements and structures of the spinal motor segments, and, conversely, a decreasing in angular values (hypolordosis) causes the stress falling.