scholarly journals Adenosine-mediated modulation of ventral horn interneurons and spinal motoneurons in neonatal mice

2015 ◽  
Vol 114 (4) ◽  
pp. 2305-2315 ◽  
Author(s):  
Emily C. Witts ◽  
Filipe Nascimento ◽  
Gareth B. Miles
Keyword(s):  
Spinal Cord ◽  
Purinergic Signaling ◽  
Presynaptic Receptors ◽  
Ventral Horn ◽  
Cellular Mechanisms ◽  
Mouse Spinal Cord ◽  
Synaptic Inputs ◽  
Adenosine Receptor Antagonist ◽  
Postsynaptic Currents

Neuromodulation allows neural networks to adapt to varying environmental and biomechanical demands. Purinergic signaling is known to be an important modulatory system in many parts of the CNS, including motor control circuitry. We have recently shown that adenosine modulates the output of mammalian spinal locomotor control circuitry (Witts EC, Panetta KM, Miles GB. J Neurophysiol 107: 1925–1934, 2012). Here we investigated the cellular mechanisms underlying this adenosine-mediated modulation. Whole cell patch-clamp recordings were performed on ventral horn interneurons and motoneurons within in vitro mouse spinal cord slice preparations. We found that adenosine hyperpolarized interneurons and reduced the frequency and amplitude of synaptic inputs to interneurons. Both effects were blocked by the A1-type adenosine receptor antagonist DPCPX. Analysis of miniature postsynaptic currents recorded from interneurons revealed that adenosine reduced their frequency but not amplitude, suggesting that adenosine acts on presynaptic receptors to modulate synaptic transmission. In contrast to interneurons, recordings from motoneurons revealed an adenosine-mediated depolarization. The frequency and amplitude of synaptic inputs to motoneurons were again reduced by adenosine, but we saw no effect on miniature postsynaptic currents. Again these effects on motoneurons were blocked by DPCPX. Taken together, these results demonstrate differential effects of adenosine, acting via A1 receptors, in the mouse spinal cord. Adenosine has a general inhibitory action on ventral horn interneurons while potentially maintaining motoneuron excitability. This may allow for adaptation of the locomotor pattern generated by interneuronal networks while helping to ensure the maintenance of overall motor output.

Complementary expression of transmembrane ephrins and their receptors in the mouse spinal cord: a possible role in constraining the orientation of longitudinally projecting axons

Development ◽  
2000 ◽  
Vol 127 (7) ◽  
pp. 1397-1410 ◽  
Author(s):  
R. Imondi ◽  
C. Wideman ◽  
Z. Kaprielian
Keyword(s):  
Spinal Cord ◽  
Floor Plate ◽  
Plate Boundaries ◽  
Eph Receptors ◽  
Axon Pathfinding ◽  
Mouse Spinal Cord ◽  
Commissural Axon ◽  
Ligand Interactions ◽  
Ventral Funiculus

In the developing spinal cord, axons project in both the transverse plane, perpendicular to the floor plate, and in the longitudinal plane, parallel to the floor plate. For many axons, the floor plate is a source of long- and short-range guidance cues that govern growth along both dimensions. We show here that B-class transmembrane ephrins and their receptors are reciprocally expressed on floor plate cells and longitudinally projecting axons in the mouse spinal cord. During the period of commissural axon pathfinding, B-class ephrin protein is expressed at the lateral floor plate boundaries, at the interface between the floor plate and the ventral funiculus. In contrast, B-class Eph receptors are expressed on decussated commissural axon segments projecting within the ventral funiculus, and on ipsilaterally projecting axons constituting the lateral funiculus. Soluble forms of all three B-class ephrins bind to, and induce the collapse of, commissural growth cones in vitro. The collapse-inducing activity associated with B-class ephrins is likely to be mediated by EphB1. Taken together, these data support a possible role for repulsive B-class Eph receptor/ligand interactions in constraining the orientation of longitudinal axon projections at the ventral midline.

Intrinsic Properties Shape the Firing Pattern of Ventral Horn Interneurons From the Spinal Cord of the Adult Turtle

2006 ◽  
Vol 96 (5) ◽  
pp. 2670-2677 ◽  
Author(s):  
Morten Smith ◽  
Jean-François Perrier
Keyword(s):  
Spinal Cord ◽  
Activity Patterns ◽  
Ventral Horn ◽  
Inward Rectification ◽  
Intrinsic Properties ◽  
Patch Clamp Technique ◽  
Firing Patterns ◽  
Pharmacological Tests ◽  
Low Threshold

Interneurons in the ventral horn of the spinal cord play a central role in motor control. In adult vertebrates, their intrinsic properties are poorly described because of the lack of in vitro preparations from the spinal cord of mature mammals. Taking advantage of the high resistance to anoxia in the adult turtle, we used a slice preparation from the spinal cord. We used the whole cell blind patch-clamp technique to record from ventral horn interneurons. We characterized their firing patterns in response to depolarizing current pulses and found that all the interneurons fired repetitively. They displayed bursting, adapting, delayed, accelerating, or oscillating firing patterns. By combining electrophysiological and pharmacological tests, we showed that interneurons expressed slow inward rectification, plateau potential, voltage-sensitive transient outward rectification, and low-threshold spikes. These results demonstrate a diversity of intrinsic properties that may enable a rich repertoire of activity patterns in the network of ventral horn interneurons.

scholarly journals Presynaptic Angiotensin II AT1 Receptors Enhance Inhibitory and Excitatory Synaptic Neurotransmission to Motoneurons and Other Ventral Horn Neurons in Neonatal Rat Spinal Cord

2005 ◽  
Vol 94 (2) ◽  
pp. 1405-1412 ◽  
Author(s):  
Murat Oz ◽  
Keun-Hang Yang ◽  
Michael J. O'Donovan ◽  
Leo P. Renaud
Keyword(s):  
Spinal Cord ◽  
Angiotensin Ii ◽  
Ventral Horn ◽  
Synaptic Activity ◽  
Neonatal Rat ◽  
Ang Ii ◽  
Synaptic Neurotransmission ◽  
Excitatory Neurotransmission ◽  
Ventral Spinal Cord

In neonatal spinal cord, we previously reported that exogenous angiotensin II (ANG II) acts at postsynaptic AT1 receptors to depolarize neonatal rat spinal ventral horn neurons in vitro. This study evaluated an associated increase in synaptic activity. Patch clamp recordings revealed that 38/81 thoracolumbar (T7–L5) motoneurons responded to bath applied ANG II (0.3–1 μM; 30 s) with a prolonged (5–10 min) and reversible increase in spontaneous postsynaptic activity, selectively blockable with Losartan ( n = 5) but not PD123319 ( n = 5). ANG-II-induced events included both spontaneous inhibitory (IPSCs; n = 6) and excitatory postsynaptic currents (EPSCs; n = 5). While most ANG induced events were tetrodotoxin-sensitive, ANG induced a significant tetrodotoxin-resistant increase in frequency but not amplitude of miniature IPSCs ( n = 7/13 cells) and EPSCs ( n = 2/7 cells). In 35/77 unidentified neurons, ANG II also induced a tetrodotoxin-sensitive and prolonged increase in their spontaneous synaptic activity that featured both IPSCs ( n = 5) and EPSCs ( n = 4) when tested in the presence of selective amino acid receptor antagonists. When tested in the presence of tetrodotoxin, ANG II was noted to induce a significant increase in the frequency but not the amplitude of mIPSCs ( n = 9) and mEPSCs ( n = 8). ANG also increased spontaneous motor activity from isolated mouse lumbar ventral rootlets. Collectively, these observations support the existence of a wide pre- and postsynaptic distribution of ANG II AT1 receptors in neonatal ventral spinal cord that are capable of influencing both inhibitory and excitatory neurotransmission.

scholarly journals Glycinergic Miniature Synaptic Currents and Receptor Cluster Sizes Differ Between Spinal Cord Interneurons

1999 ◽  
Vol 82 (1) ◽  
pp. 312-319 ◽  
Author(s):  
Sharon Oleskevich ◽  
Francisco J. Alvarez ◽  
Bruce Walmsley
Keyword(s):  
Spinal Cord ◽  
Glycine Receptor ◽  
Structural Features ◽  
Ventral Horn ◽  
Electrophysiological Recording ◽  
Rat Spinal Cord ◽  
Whole Cell Patch Clamp ◽  
Structural And Functional Properties ◽  
Receptor Clusters

The structural features of a synaptic connection between central neurons play an important role in determining the strength of the connection. In the present study, we have examined the relationship between the structural and functional properties of glycinergic synapses in the rat spinal cord. We have analyzed the structure of glycinergic receptor clusters on rat ventral horn interneurons using antibodies against the glycine receptor clustering protein, gephyrin. We have examined the properties of quantal glycinergic currents generated at these synapses using whole cell patch-clamp recordings of miniature postsynaptic inhibitory currents (mIPSCs) in rat spinal cord slices in vitro. Our immunolabeling results demonstrate that there is a considerable variability in the size of glycine receptor clusters within individual neurons. Furthermore there are large differences in the mean cluster size between neurons. These observations are paralleled closely by recordings of glycinergic mIPSCs. The mIPSC amplitude varies significantly within and between neurons. Results obtained using combined immunolabeling and electrophysiological recording on the same neurons show that cells with small glycine receptor clusters concurrently exhibit small mIPSCs. Our results suggest that the differences in the size of glycinergic receptor clusters may constitute an important factor contributing to the observed differences in mIPSC amplitude among spinal cord interneurons.

scholarly journals An in vitro functionally mature mouse spinal cord preparation for the study of spinal motor networks

1999 ◽  
Vol 816 (2) ◽  
pp. 493-499 ◽  
Author(s):  
Zhiyu Jiang ◽  
Kevin P Carlin ◽  
Robert M Brownstone
Keyword(s):  
Spinal Cord ◽  
Mouse Spinal Cord ◽  
Spinal Motor ◽  
Mature Mouse

scholarly journals The Involvement of CaV1.3 Channels in Prolonged Root Reflexes and Its Potential as a Therapeutic Target in Spinal Cord Injury

2021 ◽  
Vol 15 ◽  
Author(s):  
Mingchen C. Jiang ◽  
Derin V. Birch ◽  
Charles J. Heckman ◽  
Vicki M. Tysseling
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor System ◽  
Involuntary Movement ◽  
Intracellular Recordings ◽  
Plateau Potentials ◽  
Cellular Mechanisms ◽  
Spinal Motor ◽  
Cord Injury

Spinal cord injury (SCI) results in not only the loss of voluntary muscle control, but also in the presence of involuntary movement or spasms. These spasms post-SCI involve hyperexcitability in the spinal motor system. Hyperactive motor commands post SCI result from enhanced excitatory postsynaptic potentials (EPSPs) and persistent inward currents in voltage-gated L-type calcium channels (LTCCs), which are reflected in evoked root reflexes with different timings. To further understand the contributions of these cellular mechanisms and to explore the involvement of LTCC subtypes in SCI-induced hyperexcitability, we measured root reflexes with ventral root recordings and motoneuron activities with intracellular recordings in an in vitro preparation using a mouse model of chronic SCI (cSCI). Specifically, we explored the effects of 1-(3-chlorophenethyl)-3-cyclopentylpyrimidine-2,4,6-(1H,3H,5H)-trione (CPT), a selective negative allosteric modulator of CaV1.3 LTCCs. Our results suggest a hyperexcitability in the spinal motor system in these SCI mice. Bath application of CPT displayed slow onset but dose-dependent inhibition of the root reflexes with the strongest effect on LLRs. However, the inhibitory effect of CPT is less potent in cSCI mice than in acute SCI (aSCI) mice, suggesting changes either in composition of CaV1.3 or other cellular mechanisms in cSCI mice. For intracellular recordings, the intrinsic plateau potentials, was observed in more motoneurons in cSCI mice than in aSCI mice. CPT inhibited the plateau potentials and reduced motoneuron firings evoked by intracellular current injection. These results suggest that the LLR is an important target and that CPT has potential in the therapy of SCI-induced muscle spasms.

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