scholarly journals NMDA induces persistent inward and outward currents that cause rhythmic bursting in adult rodent motoneurons

2012 ◽  
Vol 108 (11) ◽  
pp. 2991-2998 ◽  
Author(s):  
Marin Manuel ◽  
Yaqing Li ◽  
Sherif M. ElBasiouny ◽  
Katie Murray ◽  
Anna Griener ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Nmda Receptors ◽  
Outward Current ◽  
Rhythmic Activity ◽  
Fictive Locomotion ◽  
Adult Mice ◽  
Outward Currents ◽  
Persistent Inward Current ◽  
Rats And Mice ◽  
Shed Light

N-methyl-d-aspartate (NMDA) receptors are of critical importance for locomotion in the developing neonatal spinal cord in rats and mice. However, due to profound changes in the expression of NMDA receptors in development between the neonatal stages and adulthood, it is unclear whether NMDA receptors are still an important component of locomotion in the adult rodent spinal cord. To shed light on this issue, we have taken advantage of recently developed preparations allowing the intracellular recording of adult motoneurons that control the tail in the sacrocaudal spinal cord of adult mice and rats. We show that in the adult sacrocaudal spinal cord, NMDA induces rhythmic activity recorded on the ventral roots, often coordinated from left to right, as in swimming motions with the tail (fictive locomotion). The adult motoneurons themselves are intrinsically sensitive to NMDA application. That is, when motoneurons are synaptically isolated with TTX, NMDA still causes spontaneous bursts of rhythmic activity, depending on the membrane potential. We show that these bursts in motoneurons depend on an NMDA-mediated persistent inward current and are terminated by the progressive activation of a persistent outward current. These results indicate that motoneurons, along with the central pattern generator, can actively participate in the production of swimminglike locomotor activity in adult rodents.

Activity of commissural interneurons in spinal cord of Xenopus embryos

1984 ◽  
Vol 51 (6) ◽  
pp. 1257-1267 ◽  
Author(s):  
S. R. Soffe ◽  
J. D. Clarke ◽  
A. Roberts
Keyword(s):  
Spinal Cord ◽  
Rhythmic Activity ◽  
Excitatory Input ◽  
Cycle Period ◽  
Fictive Locomotion ◽  
Anatomy And Physiology ◽  
Postsynaptic Potential ◽  
Natural Stimulation ◽  
Xenopus Laevis Embryos ◽  
Stimulation Of

Horseradish peroxidase- (HRP) filled microelectrodes have been used to examine the anatomy and physiology of "commissural interneurons," a morphologically defined class of spinal cord interneuron in Xenopus laevis embryos. Commissural interneurons have unipolar cell bodies in the dorsal half of the spinal cord. Their dendrites lie in the mid to ventral parts of the lateral tracts and their axons cross the cord ventrally, T branch, and ascend and descend on the opposite side of the cord. Recordings were made from animals immobilized in tubocurarine and responding to natural stimulation with three patterns of fictive motor activity. During episodes of fictive swimming, commissural interneurons are phasically excited to fire 1 spike/cycle in phase with motor discharge on the same side and receive a midcycle inhibitory postsynaptic potential (IPSP) in phase with motor discharge on the opposite side. Rhythmic activity is superimposed on a background depolarization. During periods of synchrony, phasic excitatory input doubles in frequency so that cells fire with half the swimming cycle period. The background depolarization is generally stronger than during swimming. During periods of fictive struggling, evoked by electrical stimulation of the skin, commissural interneurons fire a burst of spikes per cycle, cells being relatively hyperpolarized when motoneurons on the opposite side are active. In response to ipsilateral skin stimulation, some cells receive an IPSP at a latency of 12-20 ms. This precedes the onset of fictive locomotion. We discuss how anatomy and activity of commissural interneurons is suitable for a reciprocal inhibitory role.

scholarly journals How does the Lamprey Central Nervous System make the Lamprey Swim?

1984 ◽  
Vol 112 (1) ◽  
pp. 337-357 ◽  
Author(s):  
STEN GRILLNER ◽  
PETER WALLÉN
Keyword(s):  
Spinal Cord ◽  
Nmda Receptor ◽  
Morphological Characteristics ◽  
Rhythmic Activity ◽  
The Body ◽  
Fictive Locomotion ◽  
Motor Patterns ◽  
Motor Neurones ◽  
Receptor Blockers

The lamprey spinal cord, in isolation or with the brainstem, can be used in vitro. The motor patterns underlying the swimming movements can be elicited by: (1) a pharmacological activation of a specific type of neuronal receptor (NMDA-receptor), that may in other systems give rise to an unstable membrane potential, (2) by stimulation of the brainstem or (3) by tactile activation of skin regions left innervated. In the latter case the initiation of ‘fictive’ swimming is partially caused by a release of a transmitter activating NMDA-receptors, as judged by the effect of NMDA-receptor blockers. The central pattern generator (CPG) is strongly influenced by feedback from mechanosensitive elements, which at least partially reside within the spinal cord. The edge cell in the lamprey spinal cord serves as an intraspinal mechanoreceptor. The ability to generate a coordinated motor output is distributed, since spinal cord sections down to 1.5–2 segments can be made to generate alternating activity. Motor neurones receive an approximately synchronous alternating excitatory and inhibitory drive in each swim cycle and do not appear to be part of the CPG. Motor neurones supplying different parts of the body wall on the same side of a body segment have different morphology with ramifications around different descending axons. The input drive signal during fictive locomotion to motor neurones located close to each other but with different morphological characteristics may differ substantially with regard to the γ-relationship (±25%) and the shape of the oscillation. This implies that even at a segmental level motor neurones may be further subdivided, and furthermore that the ipsilateral network generating the drive signal to ipsilateral motor neurones generates a more complex and individualized output than previously assumed. Motor neurones are not part of the rhythm-generating circuit. The large identifiable interneurones are not required for rhythmic activity to occur although they may be phasically active in the swim cycle. The small segmental interneurones have not yet been completely characterized. Many are phasically active during ‘fictive locomotion’ and lack an apparent axon. Their phase relationships in relation to the burst patterns vary over the entire swim cycle.

Ionic currents in identified swimmeret motor neurones of the crayfish Pacifastacus leniusculus

1995 ◽  
Vol 198 (7) ◽  
pp. 1483-1492 ◽  
Author(s):  
A Chrachri
Keyword(s):  
Time Course ◽  
Outward Current ◽  
Rhythmic Activity ◽  
Ionic Currents ◽  
Power Stroke ◽  
Transient Outward Current ◽  
Patch Clamp Technique ◽  
Outward Currents ◽  
Inward Currents ◽  
Motor Neurones

Ionic currents from freshly isolated and identified swimmeret motor neurones were characterized using a whole-cell patch-clamp technique. Two outward currents could be distinguished. A transient outward current was elicited by delivering depolarizing voltage steps from a holding potential of -80 mV. This current was inactivated by holding the cells at a potential of -40 mV and was also blocked completely by 4-aminopyridine. A second current had a sustained time course and continued to be activated at a holding potential of -40 mV. This current was partially blocked by tetraethylammonium. These outward currents resembled two previously described potassium currents: the K+ A-current and the delayed K+ rectifier current respectively. Two inward currents were also detected. A fast transient current was blocked by tetrodotoxin and inactivated at holding potential of -40 mV, suggesting that this is an inward Na+ current. A second inward current had a sustained time course and was affected neither by tetrodotoxin nor by holding the cell at a potential of -40 mV. This current was substantially enhanced by the addition of Ba2+ to the bath or when equimolar Ba2+ replaced Ca2+ as the charge carrier. Furthermore, this current was significantly suppressed by nifedipine. All these points suggest that this is an L-type Ca2+ current. Bath application of nifedipine into an isolated swimmeret preparation affected both the frequency of the swimmeret rhythm and the duration of power-stroke activity, suggesting an important role for the inward Ca2+ current in maintaining a regular swimmeret rhythmic activity in crayfish.

Activation of NMDA receptors elecits fictive locomotion and bistable membrane properties in the lamprey spinal cord

1985 ◽  
Vol 336 (2) ◽  
pp. 390-395 ◽  
Author(s):  
K.A. Sigvardt ◽  
S. Grillner ◽  
P. Wallén ◽  
P.A.M. Van Dongen
Keyword(s):  
Spinal Cord ◽  
Nmda Receptors ◽  
Membrane Properties ◽  
Fictive Locomotion

Spinal 5-HT7 Receptors Are Critical for Alternating Activity During Locomotion: In Vitro Neonatal and In Vivo Adult Studies Using 5-HT7 Receptor Knockout Mice

2009 ◽  
Vol 102 (1) ◽  
pp. 337-348 ◽  
Author(s):  
Jun Liu ◽  
Turgay Akay ◽  
Peter B. Hedlund ◽  
Keir G. Pearson ◽  
Larry M. Jordan
Keyword(s):  
Spinal Cord ◽  
Knockout Mice ◽  
Rhythmic Activity ◽  
Neonatal Mouse ◽  
Emg Activity ◽  
In Vivo Experiments ◽  
Adult Mice ◽  
Ankle Joints

5-HT7 receptors have been implicated in the control of locomotion. Here we use 5-HT7 receptor knockout mice to rigorously test whether 5-HT acts at the 5-HT7 receptor to control locomotor-like activity in the neonatal mouse spinal cord in vitro and voluntary locomotion in adult mice. We found that 5-HT applied onto in vitro spinal cords of 5-HT7+/+ mice produced locomotor-like activity that was disrupted and subsequently blocked by the 5-HT7 receptor antagonist SB-269970. In spinal cords isolated from 5-HT7−/− mice, 5-HT produced either uncoordinated rhythmic activity or resulted in synchronous discharges of the ventral roots. SB-269970 had no effect on 5-HT-induced rhythmic activity in the 5-HT7−/− mice. In adult in vivo experiments, SB-269970 applied directly to the spinal cord consistently disrupted locomotion and produced prolonged-extension of the hindlimbs in 5-HT7+/+ but not 5-HT7−/− mice. Disrupted EMG activity produced by SB-269970 in vivo was similar to the uncoordinated rhythmic activity produced by the drug in vitro. Moreover, 5-HT7−/− mice displayed greater maximal extension at the hip and ankle joints than 5-HT7+/+ animals during voluntary locomotion. These results suggest that spinal 5-HT7 receptors are required for the production and coordination of 5-HT-induced locomotor-like activity in the neonatal mouse and are important for the coordination of voluntary locomotion in adult mice. We conclude that spinal 5-HT7 receptors are critical for alternating activity during locomotion.

scholarly journals Differential Effects of Alpha 1-Adrenoceptor Antagonists on the Postsynaptic Sensitivity: Using Slice Patch-Clamp Technique for Inhibitory Postsynaptic Current in Substantia Gelatinosa Neurons From Lumbosacral Spinal Cord in Rats

2020 ◽  
Vol 24 (2) ◽  
pp. 127-134
Author(s):  
Daisuke Uta ◽  
Tsuyoshi Hattori ◽  
Megumu Yoshimura
Keyword(s):  
Spinal Cord ◽  
Patch Clamp ◽  
Pearson Correlation ◽  
Outward Current ◽  
Substantia Gelatinosa ◽  
Patch Clamp Technique ◽  
Male Adult ◽  
Lumbosacral Spinal Cord ◽  
Inhibitory Postsynaptic Current ◽  
Outward Currents

Purpose: Alpha1-adrenoceptors participate in improving storage symptoms of male lower urinary tract symptoms. However, the mechanism of action of these compounds remains unclear. The goal of the present study was to clarify the effect of α1- adrenoceptor antagonists on γ-aminobutyric acid (GABA)/glycine-mediated outward currents of the inhibitory postsynaptic current (IPSC) in substantia gelatinosa (SG) neurons from the lumbosacral spinal cord in rats.Methods: Male adult Sprague-Dawley rats were used. Blind whole-cell patch-clamp recordings were performed in SG neurons from isolated spinal cord slice preparations. IPSCs were recorded in individual SG neurons to which naftopidil (100μM), tamsulosin (100μM), silodosin (30μM), or prazosin (10μM) were applied sequentially with intervening washout periods. Strychnine (2μM), bicuculline (10μM), or tetrodotoxin (TTX)(1μM) were added before naftopidil. Individual outward currents were analyzed.Results: The bath application of naftopidil, yielded outward IPSCs in 13 of 52 SG neurons. The naftopidil response was unchanged in the presence of TTX. Regression analysis of the outward currents between the 1st and 2nd applications of naftopidil revealed a Pearson correlation coefficient of 0.996 with a line slope of 0.983. The naftopidil-induced outward current was attenuated in the presence of strychnine and/or bicuculline. The GABA/glycine-mediated outward currents induced by tamsulosin, silodosin, and prazosin were smaller than those obtained with naftopidil.Conclusions: Naftopidil-induced GABA/glycine-mediated outward currents in a subset of SG neurons prepared from the L6– S1 level of rat spinal cord. The results indicated that α1-adrenoceptor antagonists, particularly naftopidil, induce neural suppression (in part) by mediating hyperpolarization. The response is associated with glycinergic and/or GABAergic neural transmission. Naftopidil may suppress the micturition reflex and improve urinary storage symptoms as a subsidiary effect resulting from hyperpolarization in SG neurons of the spinal cord.

Activation of NMDA receptors is required for the initiation and maintenance of walking-like activity in the mudpuppy (Necturus Maculatus)

2004 ◽  
Vol 82 (8-9) ◽  
pp. 637-644 ◽  
Author(s):  
Igor Lavrov ◽  
Jianguo Cheng
Keyword(s):  
Spinal Cord ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Rhythmic Activity ◽  
Nmda Receptor Antagonist ◽  
Glycine Site ◽  
Burst Frequency ◽  
Selective Antagonist ◽  
Dependent Inhibition ◽  
Dose Dependent

We hypothesized that blocking the activation of N-methyl-D-aspartate (NMDA) receptors prevents the initiation of walking-like activity and abolishes the ongoing rhythmic activity in the spinal cord - forelimb preparation from the mudpuppy. Robust walking-like movements of the limb and rhythmic alternating elbow flexor–extensor EMG pattern characteristic of walking were elicited when continuous perfusion of the spinal cord with solution containing D-glutamate. The frequency of the walking-like activity was dose-dependent on the concentration of D-glutamate in the bath over a range of 0.2 to 0.9 mmol/L. Elevation of potassium concentrations failed to induce walking-like activity. Application of the selective antagonist 2-amino-5-phosphonovalerate (AP-5) produced dose-dependent block of the initiation and maintenance of walking-like activity induced by D-glutamate. Complete block of the activity was achieved when the concentration of AP-5 reached 20 µmol/L. Furthermore, application of L-701,324 (a selective antagonist of the strychnine-insensitive glycine site of NMDA receptor) (1–10 µmol/L) also resulted in complete block of the walking-like activity. In contrast, application of the non-NMDA receptor antagonist 6-cyno-7-nitroquinoxaline-2,3-dione (CNQX) (1–50 µmol/L) induced a dose-dependent inhibition of the burst frequency but failed to result in a complete block. Only at concentration as high as 100 µmol/L, did CNQX cause complete block of the rhythmic activity, presumably through nonspecific action on the strychnine-insensitive glycine site of NMDA receptors. These results suggest that activation of NMDA receptors is required for the initiation and maintenance of walking-like activity. Operation of non-NMDA receptors plays a powerful role in the modulation of the walking-like activity in the mudpuppy.Key words: locomotion, central pattern generator, spinal cord, mudpuppy, glutamate, glycine, N-methyl-D-aspartate (NMDA)-receptor, 2-amino-5-phosphonovalerate (AP-5), 6-cyno-7-nitroquinoxaline-2,3-dione (CNQX).

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