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.

The effects of hydrogen ion on spinal neurons

1980 ◽  
Vol 58 (6) ◽  
pp. 650-655 ◽  
Author(s):  
K. C. Marshall ◽  
I. Engberg
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Neuronal Excitability ◽  
Input Resistance ◽  
Hydrogen Ion ◽  
Intracellular Recordings ◽  
Spinal Neurons ◽  
Number Of Cells

The effects of iontophoretically applied hydrogen ion (H+) on neuronal excitability were studied in the spinal cord of cats. The activity of extracellularly recorded neurons of the dorsal horn was either depressed or enhanced by H+ and in most cases of enhancement there was a preceding phase of depression. During intracellular recordings from motoneurons it was found that H+ application usually caused a hyperpolarization accompanied by an increase in cell input resistance. In a smaller number of cells the hyperpolarization was succeeded by a depolarization that was coupled with a decrease in input resistance. In some neurons it was shown that the depolarizing phase was more prominent and had a shorter latency when larger currents were used to eject H+. The varied reports from earlier studies of excitation or inhibition of neuronal excitability by H+ may be in part explainable by our observations that the effects may depend on the concentrations of H+ used.

scholarly journals Metabotropic glutamate receptor 5 regulates excitability and Kv4.2-containing K+ channels primarily in excitatory neurons of the spinal dorsal horn

2011 ◽  
Vol 105 (6) ◽  
pp. 3010-3021 ◽  
Author(s):  
Hui-Juan Hu ◽  
Robert W. Gereau
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Neuronal Excitability ◽  
Gabaergic Neurons ◽  
Erk Signaling ◽  
Metabotropic Glutamate ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Excitatory Neurons

Metabotropic glutamate (mGlu) receptors play important roles in the modulation of nociception. Previous studies demonstrated that mGlu5 modulates nociceptive plasticity via activation of ERK signaling. We have reported recently that the Kv4.2 K+ channel subunit underlies A-type currents in spinal cord dorsal horn neurons and that this channel is modulated by mGlu5-ERK signaling. In the present study, we tested the hypothesis that modulation of Kv4.2 by mGlu5 occurs in excitatory spinal dorsal horn neurons. With the use of a transgenic mouse strain expressing enhanced green fluorescent protein (GFP) under control of the promoter for the γ-amino butyric acid (GABA)-synthesizing enzyme, glutamic acid decarboxylase 67 (GAD67), we found that these GABAergic neurons express less Kv4.2-mediated A-type current than non-GAD67-GFP neurons. Furthermore, the mGlu1/5 agonist, (R,S)-3,5-dihydroxyphenylglycine, had no modulatory effects on A-type currents or neuronal excitability in this subgroup of GABAergic neurons but robustly modulated A-type currents and neuronal excitability in non-GFP-expressing neurons. Immunofluorescence studies revealed that Kv4.2 was highly colocalized with markers of excitatory neurons, such as vesicular glutamate transporter 1/2, PKCγ, and neurokinin 1, in cultured dorsal horn neurons. These results indicate that mGlu5-Kv4.2 signaling is associated with excitatory dorsal horn neurons and suggest that the pronociceptive effects of mGlu5 activation in the spinal cord likely involve enhanced excitability of excitatory neurons.

Multiple Firing Patterns in Deep Dorsal Horn Neurons of the Spinal Cord: Computational Analysis of Mechanisms and Functional Implications

2010 ◽  
Vol 104 (4) ◽  
pp. 1978-1996 ◽  
Author(s):  
Yann Le Franc ◽  
Gwendal Le Masson
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Information Transfer ◽  
Network Effects ◽  
Neuronal Response ◽  
Sensory Information ◽  
Firing Patterns ◽  
Dorsal Horn Neurons ◽  
The Impact

Deep dorsal horn relay neurons (dDHNs) of the spinal cord are known to exhibit multiple firing patterns under the control of local metabotropic neuromodulation: tonic firing, plateau potential, and spontaneous oscillations. This work investigates the role of interactions between voltage-gated channels and the occurrence of different firing patterns and then correlates these two phenomena with their functional role in sensory information processing. We designed a conductance-based model using the NEURON software package, which successfully reproduced the classical features of plateau in dDHNs, including a wind-up of the neuronal response after repetitive stimulation. This modeling approach allowed us to systematically test the impact of conductance interactions on the firing patterns. We found that the expression of multiple firing patterns can be reproduced by changes in the balance between two currents (L-type calcium and potassium inward rectifier conductances). By investigating a possible generalization of the firing state switch, we found that the switch can also occur by varying the balance of any hyperpolarizing and depolarizing conductances. This result extends the control of the firing switch to neuromodulators or to network effects such as synaptic inhibition. We observed that the switch between the different firing patterns occurs as a continuous function in the model, revealing a particular intermediate state called the accelerating mode. To characterize the functional effect of a firing switch on information transfer, we used correlation analysis between a model of peripheral nociceptive afference and the dDHN model. The simulation results indicate that the accelerating mode was the optimal firing state for information transfer.

Pathophysiology of Pain and Pain Pathways

2018 ◽  
Author(s):  
Paula Trigo Blanco ◽  
Maricarmen Roche Rodriguez ◽  
Nalini Vadivelu
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Peripheral Nervous System ◽  
Dorsal Horn ◽  
Emotional Response ◽  
Protective Function ◽  
Medullary Dorsal Horn ◽  
Pain Pathways ◽  
Nociceptive Information

Pain is a distressing experience and an important cause of suffering and disability. Pain usually signals the presence of injury or disease and generates a complex physiologic and emotional response. It has a protective function in order to restore homeostasis at the autonomic and psychological levels. This chapter reviews the physiology and mechanisms of pain, as well as the pathways in the central and peripheral nervous system that transmit nociceptive information. The chapter divides the pain anatomical pathways into the peripheral nervous system, the spinal cord with the medullary dorsal horn system, and the ascending and supraspinal system. The authors explain the pain pathways as a three-neuron pathway that carries noxious information from the periphery to the cerebral cortex. This chapter defines important concepts such as sensitization, hyperalgesia, and allodynia, as well as describes the modulation process of nociception.

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 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 Patrick David Wall. 5 April 1925—8 August 2001

2021 ◽  
Author(s):  
Maria Fitzgerald
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Sensory Input ◽  
Molecular Genetic ◽  
Sensory Information ◽  
Spinal Cord Dorsal Horn ◽  
Genetic Dissection ◽  
Sensory Inputs ◽  
Gate Control Theory ◽  
The Usa

Patrick (Pat) Wall was a neurophysiologist and true pioneer in the science of pain. He discovered that the sensory information arising from receptors in our body, such as those for touch and heat, could be modified, or ‘gated’, in the spinal cord by other sensory inputs and also by information descending from the brain; this meant, as is now well recognized, that the final sensory experience is not necessarily predictable from the original pain-eliciting sensory input. He used this to explain the poor relationship between injury and pain, and to illustrate the fallacy of judging what someone ‘should’ be feeling from the sensory input alone. In 1969, together with his colleague, Ron Melzack, Pat proposed the ‘gate control theory of pain’ and the circuit diagram that summarized how central spinal cord circuits can modulate sensory inputs. Later on, he began to regret that ‘goddamned diagram’, which had come to dominate his life and work, but, like all great models, it paved the way for the future. Now, over 50 years after it was first published, molecular genetic dissection of dorsal horn neuronal circuitry has indisputably confirmed that sensory inputs are indeed ‘gated’ in the spinal cord dorsal horn. Through a career that started with a medical degree in Oxford, followed by almost 20 years at Yale and MIT in the USA, and continued at University College London, Pat Wall was a highly influential, critical, creative and original thinker who revolutionized our understanding of the relationship between injury and pain, and who also became a champion for all who suffered from chronic pain.

Presynaptic and Interactive Peptidergic Modulation of Reticulospinal Synaptic Inputs in the Lamprey

2000 ◽  
Vol 83 (5) ◽  
pp. 2497-2507 ◽  
Author(s):  
David Parker
Keyword(s):  
Spinal Cord ◽  
Brain Stem ◽  
Peptide Yy ◽  
Input Resistance ◽  
Ventral Root ◽  
Interactive Effects ◽  
Inhibitory Effects ◽  
Spinal Neurons ◽  
Root Responses ◽  
The Brain

The modulatory effects of neuropeptides on descending inputs to the spinal cord have been examined by making paired recordings from reticulospinal axons and spinal neurons in the lamprey. Four peptides were examined; peptide YY (PYY) and cholecystokinin (CCK), which are contained in brain stem reticulospinal neurons, and calcitonin-gene–related peptide (CGRP) and neuropeptide Y (NPY), which are contained in primary afferents and sensory interneurons, respectively. Each of the peptides reduced the amplitude of monosynaptic reticulospinal-evoked excitatory postsynaptic potentials (EPSPs). The modulation appeared to be presynaptic, because postsynaptic input resistance and membrane potential, the amplitude of the electrical component of the EPSP, postsynaptic responses to glutamate, and spontaneous miniature EPSP amplitudes were unaffected. In addition, none of the peptides affected the pattern of N-methyl-d-aspartate (NMDA)–evoked locomotor activity in the isolated spinal cord. Potential interactions between the peptides were also examined. The “brain stem peptides” CCK and PYY had additive inhibitory effects on reticulospinal inputs, as did the “sensory peptides” CGRP and NPY. Brain stem peptides also had additive inhibitory effects when applied with sensory peptides. However, sensory peptides increased or failed to affect the amplitude of reticulospinal inputs in the presence of the brain stem peptides. These interactive effects also appear to be mediated presynaptically. The functional consequence of the peptidergic modulation was investigated by examining spinal ventral root responses elicited by brain stem stimulation. CCK and CGRP both reduced ventral root responses, although in interaction both increased the response. These results thus suggest that neuropeptides presynaptically influence the descending activation of spinal locomotor networks, and that they can have additive or novel interactive effects depending on the peptides examined and the order of their application.

Activation of pharmacologically distinct metabotropic glutamate receptors depresses reticulospinal-evoked monosynaptic EPSPs in the lamprey spinal cord

1996 ◽  
Vol 76 (6) ◽  
pp. 3834-3841 ◽  
Author(s):  
P. Krieger ◽  
A. el Manira ◽  
S. Grillner
Keyword(s):  
Spinal Cord ◽  
Synaptic Transmission ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Input Resistance ◽  
Spinal Neurons ◽  
Metabotropic Glutamate ◽  
Apparent Change ◽  
Glutamatergic Synaptic Transmission ◽  
Presynaptic Mechanisms

1. Different metabotropic glutamate receptors (mGluRs) can modulate synaptic transmission in different regions in the CNS, but their roles at individual synaptic connections have not been detailed. We used paired intracellular recordings from reticulospinal axons and their postsynaptic target neurons in the lamprey spinal cord to investigate the effects of mGluR activation on glutamatergic synaptic transmission. 2. The mGluR agonists (1S,3R)-1-aminocyclopentane-1,3-dicarboxyylic acid [(1S,3R)-ACPD] and L(+)-2-amino-4-phosphonobutyric acid (L-AP4) both reduced the amplitude of monosynaptic excitatory postsynaptic potentials (EPSPs) elicited by stimulation of single reticulospinal axons. The depression of monosynaptic unitary EPSPs occurred without any apparent change in the input resistance of postsynaptic neurons. Furthermore, the mGluR agonists did not affect the amplitude of (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced depolarizations. Taken together, these results thus suggest that (1S,3R)-ACPD and L-AP4 depress reticulospinal synaptic transmission via presynaptic mechanisms. 3. (2S,1'S,2'S)-2-(carboxycyclopropyl) glycine (L-CCG-I), which selectively activates group II mGluRs, also reduced the amplitude of reticulospinal-evoked EPSPs without any apparent change in the input resistance or membrane potential of the postsynaptic neuron. 4. The mGluR antagonist alpha-methyl-L-AP4 blocked the depression induced by L-AP4 but not that induced by (1S,3R)-ACPD. Furthermore, the effects of coapplication of (1S,3R)-ACPD and L-AP4 were additive, suggesting that they inhibit synaptic transmission by an action on pharmacologically distinct mGluRs. 5. These results provide evidence for the colocalization of at least two different subtypes of presynaptic mGluRs on a single reticulospinal axon in the lamprey. These presynaptic mGluRs could serve as glutamatergic autoreceptors limiting the extent of reticulospinal-mediated excitation of spinal neurons.

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