scholarly journals Genetically identified spinal interneurons integrating tactile afferents for motor control

2015 ◽  
Vol 114 (6) ◽  
pp. 3050-3063 ◽  
Author(s):  
Tuan V. Bui ◽  
Nicolas Stifani ◽  
Izabela Panek ◽  
Carl Farah
Keyword(s):  
Spinal Cord ◽  
Motor Control ◽  
Sensory Information ◽  
Spinal Neuron ◽  
Spinal Neurons ◽  
Tactile Information ◽  
Spinal Interneurons ◽  
Motor Circuits ◽  
Neuron Populations ◽  
Genetic Techniques

Our movements are shaped by our perception of the world as communicated by our senses. Perception of sensory information has been largely attributed to cortical activity. However, a prior level of sensory processing occurs in the spinal cord. Indeed, sensory inputs directly project to many spinal circuits, some of which communicate with motor circuits within the spinal cord. Therefore, the processing of sensory information for the purpose of ensuring proper movements is distributed between spinal and supraspinal circuits. The mechanisms underlying the integration of sensory information for motor control at the level of the spinal cord have yet to be fully described. Recent research has led to the characterization of spinal neuron populations that share common molecular identities. Identification of molecular markers that define specific populations of spinal neurons is a prerequisite to the application of genetic techniques devised to both delineate the function of these spinal neurons and their connectivity. This strategy has been used in the study of spinal neurons that receive tactile inputs from sensory neurons innervating the skin. As a result, the circuits that include these spinal neurons have been revealed to play important roles in specific aspects of motor function. We describe these genetically identified spinal neurons that integrate tactile information and the contribution of these studies to our understanding of how tactile information shapes motor output. Furthermore, we describe future opportunities that these circuits present for shedding light on the neural mechanisms of tactile processing.

scholarly journals Spinal neuron-glia-immune interaction in cross-organ sensitization

2020 ◽  
Vol 319 (6) ◽  
pp. G748-G760
Author(s):  
Liya Y. Qiao ◽  
Namrata Tiwari
Keyword(s):  
Spinal Cord ◽  
Glial Cells ◽  
Sensory Information ◽  
Spinal Nerve ◽  
Primary Afferents ◽  
Leg Pain ◽  
Spinal Neuron ◽  
Afferent Neurons ◽  
Satellite Glial Cells ◽  
Integrative Processing

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), historically considered as regional gastrointestinal disorders with heightened colonic sensitivity, are increasingly recognized to have concurrent dysfunction of other visceral and somatic organs, such as urinary bladder hyperactivity, leg pain, and skin hypersensitivity. The interorgan sensory cross talk is, at large, termed “cross-organ sensitization.” These organs, anatomically distant from one another, physiologically interlock through projecting their sensory information into dorsal root ganglia (DRG) and then the spinal cord for integrative processing. The fundamental question of how sensitization of colonic afferent neurons conveys nociceptive information to activate primary afferents that innervate distant organs remains ambiguous. In DRG, primary afferent neurons are surrounded by satellite glial cells (SGCs) and macrophage accumulation in response to signals of injury to form a neuron-glia-macrophage triad. Astrocytes and microglia are major resident nonneuronal cells in the spinal cord to interact, physically and chemically, with sensory synapses. Cumulative evidence gathered so far indicate the indispensable roles of paracrine/autocrine interactions among neurons, glial cells, and immune cells in sensory cross-activation. Dichotomizing afferents, sensory convergency in the spinal cord, spinal nerve comingling, and extensive sprouting of central axons of primary afferents each has significant roles in the process of cross-organ sensitization; however, more results are required to explain their functional contributions. DRG that are located outside the blood-brain barrier and reside upstream in the cascade of sensory flow from one organ to the other in cross-organ sensitization could be safer therapeutic targets to produce less central adverse effects.

Spinal Fos labeling and penile erection elicited by stimulation of dorsal nerve of the rat penis

1997 ◽  
Vol 272 (5) ◽  
pp. R1425-R1431 ◽  
Author(s):  
O. Rampin ◽  
S. Gougis ◽  
F. Giuliano ◽  
J. P. Rousseau
Keyword(s):  
Spinal Cord ◽  
Inhibitory Control ◽  
Penile Erection ◽  
Sensory Information ◽  
Immunocytochemical Staining ◽  
Spinal Neurons ◽  
Afferent Limb ◽  
Sacral Parasympathetic Nucleus ◽  
Dorsal Nerve ◽  
Stimulation Of

Penile afferents present in the dorsal nerve of the penis (DNP) convey sensory information from the penis to the spinal cord and represent the afferent limb of reflexive erections. Immunocytochemical staining of Fos was used to identify spinal neurons that receive excitatory inputs from the DNP in anesthetized rats. Intracavernous pressure (ICP) was recorded as an index of erection. Dissection as well as stimulation of the DNP elicited a comparable increase in Fos staining. Labeling was present in the dorsal horn, the dorsal gray commissure, and the sacral parasympathetic nucleus, supporting the hypothesis of direct or indirect afferent projection from the penis and penile sheath in these areas. No change in ICP was observed in these rats. Stimulation of the DNP elicited both increased Fos labeling and ICP after spinalization, demonstrating the presence of a supraspinal inhibitory control exerted on the polysynaptic intraspinal circuitry responsible for reflexive penile erection.

scholarly journals Electrical maturation of spinal neurons in the human fetus: comparison of ventral and dorsal horn

2015 ◽  
Vol 114 (5) ◽  
pp. 2661-2671 ◽  
Author(s):  
M. A. Tadros ◽  
R. Lim ◽  
D. I. Hughes ◽  
A. M. Brichta ◽  
R. J. Callister
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Neuronal Excitability ◽  
Sensory Information ◽  
Input Resistance ◽  
Spinal Neurons ◽  
Nociceptive Information ◽  
The Central Nervous System ◽  
Patch Clamp Electrophysiology ◽  
In Utero Development

The spinal cord is critical for modifying and relaying sensory information to, and motor commands from, higher centers in the central nervous system to initiate and maintain contextually relevant locomotor responses. Our understanding of how spinal sensorimotor circuits are established during in utero development is based largely on studies in rodents. In contrast, there is little functional data on the development of sensory and motor systems in humans. Here, we use patch-clamp electrophysiology to examine the development of neuronal excitability in human fetal spinal cords (10–18 wk gestation; WG). Transverse spinal cord slices (300 μm thick) were prepared, and recordings were made, from visualized neurons in either the ventral (VH) or dorsal horn (DH) at 32°C. Action potentials (APs) could be elicited in VH neurons throughout the period examined, but only after 16 WG in DH neurons. At this age, VH neurons discharged multiple APs, whereas most DH neurons discharged single APs. In addition, at 16–18 WG, VH neurons also displayed larger AP and after-hyperpolarization amplitudes than DH neurons. Between 10 and 18 WG, the intrinsic properties of VH neurons changed markedly, with input resistance decreasing and AP and after-hyperpolarization amplitudes increasing. These findings are consistent with the hypothesis that VH motor circuitry matures more rapidly than the DH circuits that are involved in processing tactile and nociceptive information.

Restoration of Direct Corticospinal Communication Across Sites of Spinal Injury

2019 ◽  
Author(s):  
Naveen Jayaprakash ◽  
David Nowak ◽  
Erik Eastwood ◽  
Nicholas Krueger ◽  
Zimei Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Control ◽  
Neural Progenitor Cells ◽  
Corticospinal Tract ◽  
Spinal Injury ◽  
Combined Treatment ◽  
Fine Motor ◽  
Spinal Neurons ◽  
Injury Site ◽  
A Site

Injury to the spinal cord often disrupts long-distance axon tracts that link the brain and spinal cord, causing permanent disability. Axon regeneration is then prevented by a combination of inhibitory signals that emerge at the injury site and by a low capacity for regeneration within injured neurons. The corticospinal tract (CST) is essential for fine motor control but has proven refractory to many attempted pro-regenerative treatments. Although strategies are emerging to create relay or detour circuits that re-route cortical motor commands through spared circuits, these have only partially met the challenge of restoring motor control. Here, using a murine model of spinal injury, we elevated the intrinsic regenerative ability of CST neurons by supplying a pro-regenerative transcription factor, KLF6, while simultaneously supplying injured CST axons with a growth-permissive graft of neural progenitor cells (NPCs) transplanted into a site of spinal injury. The combined treatment produced robust CST regeneration directly through the grafts and into distal spinal cord. Moreover, selective optogenetic stimulation of regenerated CST axons and single-unit electrophysiology revealed extensive synaptic integration by CST axons with spinal neurons beyond the injury site. Finally, when KLF6 was delivered to injured neurons with a highly effective retrograde vector, combined KLF6/NPC treatment yielded significant improvements in forelimb function. These findings highlight the utility of retrograde gene therapy as a strategy to treat CNS injury and establish conditions that restore functional CST communication across a site of spinal injury.Significance StatementDamage to the spinal cord results in incurable paralysis because axons that carry descending motor commands are unable to regenerate. Here we deployed a two-pronged strategy in a rodent model of spinal injury to promote regeneration by the corticospinal tract, a critical mediator of fine motor control. Delivering pro-regenerative KLF6 to injured neurons while simultaneously transplanting neural progenitor cells to injury sites resulted in robust regeneration directly through sites of spinal injury, accompanied by extensive synapse formation with spinal neurons. In addition, when KLF6 was delivered with improved retrograde gene therapy vectors, the combined treatment significantly improved forelimb function in injured animals. This work represents important progress toward restoring regeneration and motor function after spinal injury.

scholarly journals Basal protrusions mediate spatiotemporal patterns of spinal neuron differentiation

2019 ◽  
Author(s):  
Zena Hadjivasiliou ◽  
Rachel Moore ◽  
Rebecca McIntosh ◽  
Gabriel Galea ◽  
Jon Clarke ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Periodic Pattern ◽  
Spinal Neuron ◽  
Spatiotemporal Pattern ◽  
Spinal Neurons ◽  
Long Distance ◽  
Basal Surface ◽  
Spinal Cord Development ◽  
Model Support

SummaryDuring early spinal cord development, neurons of particular subtypes differentiate with a sparse periodic pattern while later neurons differentiate in the intervening space to eventually produce continuous columns of similar neurons. The mechanisms that regulate this spatiotemporal pattern are unknown. In vivo imaging of zebrafish reveals differentiating spinal neurons transiently extend two long protrusions along the basal surface of the spinal cord prior to axon initiation. These protrusions express Delta protein consistent with the possibility they influence Notch signalling at a distance of several cell diameters. Experimental reduction of laminin expression leads to smaller protrusions and shorter distances between differentiating neurons. The experimental data and a theoretical model support the proposal that the pattern of neuronal differentiation is regulated by transient basal protrusions that deliver temporally controlled lateral inhibition mediated at a distance. This work uncovers novel, stereotyped protrusive activity of new-born neurons that organizes long distance spatiotemporal patterning of differentiation.

scholarly journals An injury-induced serotonergic neuron subpopulation contributes to axon regrowth and function restoration after spinal cord injury in zebrafish

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chun-Xiao Huang ◽  
Yacong Zhao ◽  
Jie Mao ◽  
Zhen Wang ◽  
Lulu Xu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Spinal Neurons ◽  
Knock Out ◽  
Spinal Interneurons ◽  
Axonal Regrowth ◽  
Robust Model ◽  
Cord Injury ◽  
And Function

AbstractSpinal cord injury (SCI) interrupts long-projecting descending spinal neurons and disrupts the spinal central pattern generator (CPG) that controls locomotion. The intrinsic mechanisms underlying re-wiring of spinal neural circuits and recovery of locomotion after SCI are unclear. Zebrafish shows axonal regeneration and functional recovery after SCI making it a robust model to study mechanisms of regeneration. Here, we use a two-cut SCI model to investigate whether recovery of locomotion can occur independently of supraspinal connections. Using this injury model, we show that injury induces the localization of a specialized group of intraspinal serotonergic neurons (ISNs), with distinctive molecular and cellular properties, at the injury site. This subpopulation of ISNs have hyperactive terminal varicosities constantly releasing serotonin activating 5-HT1B receptors, resulting in axonal regrowth of spinal interneurons. Axon regrowth of excitatory interneurons is more pronounced compared to inhibitory interneurons. Knock-out of htr1b prevents axon regrowth of spinal excitatory interneurons, negatively affecting coordination of rostral-caudal body movements and restoration of locomotor function. On the other hand, treatment with 5-HT1B receptor agonizts promotes functional recovery following SCI. In summary, our data show an intraspinal mechanism where a subpopulation of ISNs stimulates axonal regrowth resulting in improved recovery of locomotor functions following SCI in zebrafish.

scholarly journals Evolution of lbx spinal cord expression and function

2020 ◽  
Author(s):  
José L. Juárez-Morales ◽  
Frida Weierud ◽  
Samantha England ◽  
Celia Denby ◽  
Nicole Santos ◽  
...  
Keyword(s):  
Spinal Cord ◽  
System Development ◽  
Expression Patterns ◽  
Cell Types ◽  
Nervous System Development ◽  
Spinal Neuron ◽  
Neuron Development ◽  
Spinal Neurons ◽  
Excitatory Neurons ◽  
And Function

AbstractLadybird homeobox (Lbx) transcription factors have crucial functions in muscle and nervous system development in many different animals. Amniotes have two Lbx genes, Lbx1 and Lbx2, but only Lbx1 is expressed in the spinal cord. In contrast, teleosts have three lbx genes, lbx1a, lbx1b and lbx2. In this study, we characterize the spinal cord expression of zebrafish lbx1a, lbx1b and lbx2 and show that each of these genes is expressed by distinct cell types. Our data suggest that lbx1a is expressed by dI4, dI5 and dI6 spinal interneurons, whereas lbx1b and lbx2 are primarily expressed in different spinal cord progenitor domains. We investigated the evolution of Lbx spinal cord expression patterns by examining Lbx1 and Lbx2 expression in the lesser spotted dogfish, Scyliorhinus canicula and Lbx1 expression in the tetrapod, Xenopus tropicalis. Our results suggest that zebrafish lbx1a spinal cord expression is conserved with that of Lbx1 in other vertebrates, whereas lbx1b spinal cord expression probably evolved in teleosts after the duplication of lbx1 into lbx1a and lbx1b. lbx2 spinal expression was probably acquired somewhere in the ray-finned lineage, as this gene is not expressed in the spinal cords of either amniotes or S. canicula. Consistent with its conserved spinal cord expression pattern, we also show that the spinal cord function of zebrafish lbx1a is conserved with mouse Lbx1. In zebrafish lbx1a mutants, there is a reduction of inhibitory spinal neurons and an increase in excitatory neurons, similar to the phenotype of mouse Lbx1 mutants. Interestingly, we also see a reduction of inhibitory spinal neurons in lbx1b mutants, although in this case there is not a corresponding increase in the number of excitatory neurons and lbx1a;lbx1b double mutants do not have a more severe spinal cord phenotype than lbx1a single mutants, suggesting that lbx1a and lbx1b do not act redundantly in spinal neuron development. This suggests that lbx1b and lbx1a may be required in succession for correct specification of inhibitory dI4 and dI6 interneurons, although only lbx1a is required for suppression of excitatory fates in these cells.

scholarly journals Brain fMRI during orientation selective epidural spinal cord stimulation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Antonietta Canna ◽  
Lauri J. Lehto ◽  
Lin Wu ◽  
Sheng Sang ◽  
Hanne Laakso ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Stimulation ◽  
Pain Treatment ◽  
Positive Impact ◽  
Sensory Information ◽  
Activation Patterns ◽  
Promising Tool ◽  
Cord Injury ◽  
Epidural Spinal Cord Stimulation ◽  
Brain Fmri

AbstractEpidural spinal cord stimulation (ESCS) is widely used for chronic pain treatment, and is also a promising tool for restoring motor function after spinal cord injury. Despite significant positive impact of ESCS, currently available protocols provide limited specificity and efficiency partially due to the limited number of contacts of the leads and to the limited flexibility to vary the spatial distribution of the stimulation field in respect to the spinal cord. Recently, we introduced Orientation Selective (OS) stimulation strategies for deep brain stimulation, and demonstrated their selectivity in rats using functional MRI (fMRI). The method achieves orientation selectivity by controlling the main direction of the electric field gradients using individually driven channels. Here, we introduced a similar OS approach for ESCS, and demonstrated orientation dependent brain activations as detected by brain fMRI. The fMRI activation patterns during spinal cord stimulation demonstrated the complexity of brain networks stimulated by OS-ESCS paradigms, involving brain areas responsible for the transmission of the motor and sensory information. The OS approach may allow targeting ESCS to spinal fibers of different orientations, ultimately making stimulation less dependent on the precision of the electrode implantation.

scholarly journals The emulation theory of representation: Motor control, imagery, and perception

2004 ◽  
Vol 27 (3) ◽  
pp. 377-396 ◽  
Author(s):  
Rick Grush
Keyword(s):  
Motor Control ◽  
Sensory Feedback ◽  
Sensory Input ◽  
Neural Circuits ◽  
Sensory Information ◽  
The Body ◽  
Feedback Delay ◽  
Run Off ◽  
Effects Of Feedback ◽  
The Brain

The emulation theory of representation is developed and explored as a framework that can revealingly synthesize a wide variety of representational functions of the brain. The framework is based on constructs from control theory (forward models) and signal processing (Kalman filters). The idea is that in addition to simply engaging with the body and environment, the brain constructs neural circuits that act as models of the body and environment. During overt sensorimotor engagement, these models are driven by efference copies in parallel with the body and environment, in order to provide expectations of the sensory feedback, and to enhance and process sensory information. These models can also be run off-line in order to produce imagery, estimate outcomes of different actions, and evaluate and develop motor plans. The framework is initially developed within the context of motor control, where it has been shown that inner models running in parallel with the body can reduce the effects of feedback delay problems. The same mechanisms can account for motor imagery as the off-line driving of the emulator via efference copies. The framework is extended to account for visual imagery as the off-line driving of an emulator of the motor-visual loop. I also show how such systems can provide for amodal spatial imagery. Perception, including visual perception, results from such models being used to form expectations of, and to interpret, sensory input. I close by briefly outlining other cognitive functions that might also be synthesized within this framework, including reasoning, theory of mind phenomena, and language.

Changes in serotonin-induced potentials during spinal cord development

1993 ◽  
Vol 69 (4) ◽  
pp. 1338-1349 ◽  
Author(s):  
L. Ziskind-Conhaim ◽  
B. S. Seebach ◽  
B. X. Gao
Keyword(s):  
Spinal Cord ◽  
Direct Action ◽  
Membrane Resistance ◽  
Ventral Horn ◽  
Repetitive Firing ◽  
Lumbar Spinal Cord ◽  
Receptor Subtypes ◽  
Gamma Aminobutyric Acid ◽  
Spinal Neurons ◽  
Lumbar Spinal

1. Motoneuron responses to serotonin (5-hydroxytryptamine, 5-HT), and the growth pattern of 5-HT projections into the ventral horn were studied in the isolated spinal cord of embryonic and neonatal rats. 2. 5-HT projections first appeared in lumbar spinal cord at days 16-17 of gestation (E16-E17) and were localized in the lateral and ventral funiculi. By E18, the projections had grown into the ventral horn, and at 1-2 days after birth they were in close apposition to motoneuron somata. 3. At E16-E17, slow-rising depolarizing potentials of 1-4 mV were recorded intracellularly in lumbar motoneurons in response to bath application of 5-HT. These potentials were not apparent after E18; at that time 5-HT generated long-lasting depolarizations with an average amplitude of 6 mV, and an increase of 11% in membrane resistance. Starting at E18, 5-HT also induced high-frequency fast-rising potentials that were blocked by antagonists of glutamate, gamma-aminobutyric acid, and glycine. 4. Motoneuron responses to 5-HT increased significantly after birth, when 5-HT produced an average depolarization of 19 mV and repetitive firing of action potentials. 5. Tetrodotoxin and high Mg2+ did not reduce the amplitude of the long-lasting depolarizations, which suggested that they were produced by direct action of 5-HT on motoneuron membrane. 6. At all developmental ages, 5-HT reduced the amplitude of dorsal root-evoked potentials. The suppressed responses were neither due to 5-HT-induced depolarization nor the result of a decrease in motoneuron excitability. 7. The pharmacological profile of 5-HT-induced potentials was studied with the use of various agonists and antagonists of 5-HT. The findings indicated that the actions of 5-HT on spinal neurons were mediated via multiple 5-HT receptor subtypes. 8. Our results suggested that 5-HT excited spinal neurons before 5-HT projections grew into the ventral horn. The characteristics of 5-HT-induced potentials changed, however, at the time when the density of 5-HT projections increased in the motor nuclei.

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