Modulation of calcium currents and membrane properties by substance P in the lamprey spinal cord

2013 ◽  
Vol 110 (2) ◽  
pp. 286-296 ◽  
Author(s):  
Carolina Thörn Pérez ◽  
Russell H. Hill ◽  
Sten Grillner
Keyword(s):  
Spinal Cord ◽  
Substance P ◽  
Calcium Channels ◽  
Calcium Channel ◽  
Input Resistance ◽  
Reciprocal Inhibition ◽  
Calcium Currents ◽  
Membrane Properties ◽  
Fictive Locomotion ◽  
Burst Frequency

Substance P is endogenously released within the locomotor network of the adult lamprey, accelerates the burst frequency of fictive locomotion, and reduces the reciprocal inhibition. Previous studies have shown that dopamine, serotonin, and GABA regulate calcium channels, which control neurotransmitter release, action potential duration, and slow afterhyperpolarization (sAHP). Here we examine the effect of substance P on calcium channels in motoneurons and commissural interneurons using whole cell patch clamp in the lamprey spinal cord. This study analyzed the effects of substance P on calcium currents activated in voltage clamp. We examined the calcium-dependent sAHP in current clamp, to determine the involvement of three calcium channel subtypes modulated by substance P. The effects of substance P on membrane potential and during N-methyl-d-aspartic acid (NMDA) induced oscillations were also analyzed. Depolarizing voltage steps induced inward calcium currents. Substance P reduced the currents carried by calcium by 61% in commissural interneurons and by 31% in motoneurons. Using specific calcium channel antagonists, we show that substance P reduces the sAHP primarily by inhibiting N-type (CaV2.2) channels. Substance P depolarized both motoneurons and commissural interneurons, and we present evidence that this occurs due to an increased input resistance. We also explored the effects of substance P on NMDA-induced oscillations in tetrodotoxin and found it caused a frequency increase. Thus the reduction of calcium entry by substance P and the accompanying decrease of the sAHP amplitude, combined with substance P potentiation of currents activated by NMDA, may both contribute to the increase in fictive locomotion frequency.

scholarly journals Calcium Channel Subtypes in Lamprey Sensory and Motor Neurons

1997 ◽  
Vol 78 (3) ◽  
pp. 1334-1340 ◽  
Author(s):  
A. El Manira ◽  
N. Bussières
Keyword(s):  
Spinal Cord ◽  
Calcium Channels ◽  
Calcium Channel ◽  
Sensory Neurons ◽  
Motor Neurons ◽  
Calcium Channel Antagonist ◽  
Calcium Currents ◽  
Spinal Cord Neurons ◽  
Channel Current ◽  
Dorsal Cells

El Manira, A. and N. Bussières. Calcium channel subtypes in lamprey sensory and motor neurons. J. Neurophysiol. 78: 1334–1340, 1997. Pharmacologically distinct calcium channels have been characterized in dissociated cutaneous sensory neurons and motoneurons of the larval lamprey spinal cord. To enable cell identification, sensory dorsal cells and motoneurons were selectively labeled with fluorescein-coupled dextran amine in the intact spinal cord in vitro before dissociation. Calcium channels present in sensory dorsal cells, motoneurons, and other spinal cord neurons were characterized with the use of whole cell voltage-clamp recordings and specific calcium channel agonist and antagonists. The results show that a transient low-voltage-activated (LVA) calcium current was present in a proportion of sensory dorsal cells but not in motoneurons, whereas high-voltage-activated (HVA) calcium currents were seen in all neurons recorded. The different components of HVA current were dissected pharmacologically and similar results were obtained for both dorsal cells and motoneurons. The N-type calcium channel antagonist ω-conotoxin-GVIA(ω-CgTx) blocked >70% of the HVA current. A large part of the ω-CgTx block was reversed after washout of the toxin. The L-type calcium channel antagonist nimodipine blocked ∼15% of the total HVA current. The dihydropyridine agonist (±)-BayK 8644 markedly increased the amplitude of the calcium channel current. The BayK-potentiated current was not affected by ω-CgTx, indicating that the reversibility of the ω-CgTx effect is not due to a blockade of L-type channels. Simultaneous application of ω-CgTx and nimodipine left ∼15% of the HVA calcium channel current, a small part of which was blocked by the P/Q-type channel antagonist ω-agatoxin-IVA. In the presence of the three antagonists, the persistent residual current (∼10%) was completely blocked by cadmium. Our results provide evidence for the existence of HVA calcium channels of the N, L, and P/Q types and other HVA calcium channels in lamprey sensory neurons and motoneurons. In addition, certain types of neurons express LVA calcium channels.

Differential Effects of Corticosterone on the Slow Afterhyperpolarization in the Basolateral Amygdala and CA1 Region: Possible Role of Calcium Channel Subunits

2008 ◽  
Vol 99 (2) ◽  
pp. 958-968 ◽  
Author(s):  
Lutz Liebmann ◽  
Henk Karst ◽  
Kyriaki Sidiropoulou ◽  
Neeltje van Gemert ◽  
Onno C. Meijer ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Basolateral Amygdala ◽  
Pyramidal Neurons ◽  
Input Resistance ◽  
Calcium Currents ◽  
Membrane Properties ◽  
Resting Membrane Potential ◽  
Differential Distribution ◽  
Ca1 Region ◽  
Subunit Expression

The stress hormone corticosterone increases the amplitude of the slow afterhyperpolarization (sAHP) in CA1 pyramidal neurons, without affecting resting membrane potential, input resistance, or action potential characteristics. We here examined how corticosterone affects these properties in the basolateral amygdala (BLA). In the amygdala, corticosterone does not change the AHP amplitude, nor any of the passive and active membrane properties studied. The lack of effect on the AHP is surprising since in both areas corticosterone increases high-voltage–activated sustained calcium currents, which supposedly regulate the sAHP. We wondered whether corticosterone targets different calcium channel subunits in the two areas because currents through only one of the subunits (Cav1.3) are thought to alter the AHP amplitude. In situ hybridization studies revealed that CA1 cells express Cav1.2 and Cav1.3 subunits; corticosterone does not transcriptionally regulate Cav1.2 but increases Cav1.3 expression compared with vehicle treatment. In the BLA, Cav1.3 expression was not detectable, both after control and corticosterone treatment. Cav1.2 is moderately expressed. In a modeling study, we examined putative consequences of changes in specific calcium channel subunit expression and calcium extrusion by corticosterone for the AHP in CA1 and amygdala neurons. A differential distribution and transcriptional regulation of Cav1.2 and Cav1.3 in the CA1 area versus BLA partly explain the observed differences in AHP amplitude. The functional implication of these findings could be that stress-induced arousal of activity in the BLA is more prolonged than that in the CA1 hippocampal area, so that information with an emotional component is more effectively encoded.

The spinal GABA system modulates burst frequency and intersegmental coordination in the lamprey: differential effects of GABAA and GABAB receptors

1993 ◽  
Vol 69 (3) ◽  
pp. 647-657 ◽  
Author(s):  
J. Tegner ◽  
T. Matsushima ◽  
A. el Manira ◽  
S. Grillner
Keyword(s):  
Spinal Cord ◽  
Locomotor Activity ◽  
Gabaa Receptor ◽  
Gabab Receptor ◽  
Gaba Uptake ◽  
Phase Lag ◽  
Fictive Locomotion ◽  
Burst Frequency ◽  
Intersegmental Coordination ◽  
Burst Pattern

1. The effect of spinal GABAergic neurons on the segmental neuronal network generating locomotion has been analyzed in the lamprey spinal cord in vitro. It is shown that gamma-aminobutyric acid (GABA)A- and GABAB-mediated effects influence the burst frequency and the intersegmental coordination and that the GABA system is active during normal locomotor activity. 2. Fictive locomotor activity was induced by superfusing the spinal cord with a Ringer solution containing N-methyl-D-aspartate (NMDA, 150 microM). The efferent locomotor activity was recorded by suction electrodes from the ventral roots or intracellularly from interneurons or motoneurons. If a GABA uptake blocker was added to the perfusate, the burst rate decreased. This effect was counteracted by GABAB receptor blockade by phaclofen or 2-(OH)-saclofen. If instead a GABAB receptor agonist (baclofen) was added during fictive locomotion, a depression of the burst rate occurred. It was concluded that a GABAB receptor activation due to an endogenous release of GABA caused a depression of the burst activity with a maintained well-coordinated locomotor activity. 3. If a GABAA receptor antagonist (bicuculline) is applied during fictive locomotion elicited by NMDA, a certain increase of the burst rate occurred. Conversely, if a selective GABAA agonist (muscimol) was administered, the burst rate decreased. Similarly, if the GABAA receptor activity was potentiated by activation of a benzodiazepine site by diazepam, the burst rate was reduced. If, however the GABAergic effect was first enhanced by an uptake blocker (nipecotic acid), an administration of a GABAA antagonist (bicuculline) increased the burst rate, but in addition, the burst pattern became less regular with recurrent shorter periods without clear reciprocal burst activity. The GABAA receptor activity appears important for the rate control and for permitting a regular burst pattern. 4. The intersegmental coordination in the lamprey is characterized by a rostrocaudal constant phase lag of approximately 1% of the cycle duration between the activation of consecutive segments during forward swimming. This rostrocaudal phase lag can be reversed during backward swimming, which can be induced also experimentally in the isolated spinal cord by providing a higher excitability to the caudal segments. In a split-bath configuration, a GABA uptake blocker or a GABAB agonist was administered to the rostral part of the spinal cord, which caused a reversal of the phase lag as during backward swimming. If GABAA receptors were blocked under similar conditions, the intersegmental coordination became irregular. It is concluded that an increased GABA activity in a spinal cord region can modify the intersegmental coordination.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Motoneuron output regulated by ionic channels: a modeling study of motoneuron frequency-current relationships during fictive locomotion

2018 ◽  
Vol 120 (4) ◽  
pp. 1840-1858 ◽  
Author(s):  
Yue Dai ◽  
Yi Cheng ◽  
Brent Fedirchuk ◽  
Larry M. Jordan ◽  
Junhao Chu
Keyword(s):  
Input Resistance ◽  
Ionic Channels ◽  
Motor Output ◽  
Membrane Properties ◽  
Fictive Locomotion ◽  
State Dependent ◽  
Simulation Results ◽  
The Individual ◽  
Ionic Basis ◽  
Frequency Current

Cat lumbar motoneurons display changes in membrane properties during fictive locomotion. These changes include reduction of input resistance and afterhyperpolarization, hyperpolarization of voltage threshold, and voltage-dependent excitation of the motoneurons. The state-dependent alteration of membrane properties leads to dramatic changes in frequency-current (F-I) relationship. The mechanism underlying these changes remains unknown. Using a motoneuron model combined with electrophysiological data, we investigated the channel mechanisms underlying the regulation of motoneuronal excitability and motor output. Simulation results showed that upregulation of transient sodium, persistent sodium, or Cav1.3 calcium conductances or downregulation of calcium-activated potassium or KCNQ/Kv7 potassium conductances could increase motoneuronal excitability and motor output through hyperpolarizing (left shifting) the F-I relationships or increasing the F-I slopes, whereas downregulation of input resistance or upregulation of potassium-mediated leak conductance produced the opposite effects. The excitatory phase of locomotor drive potentials (LDPs) also substantially hyperpolarized the F-I relationships and increased the F-I slopes, whereas the inhibitory phase of the LDPs had opposite effects to a similar extent. The simulation results also showed that none of the individual channel modulations could produce all the changes in the F-I relationships. The effects of modulation of Cav1.3 and KCNQ/Kv7 on F-I relationships were supported by slice experiments with the Cav1.3 agonist Bay K8644 and the KCNQ/Kv7 antagonist XE-991. The conclusion is that the varying changes in F-I relationships during fictive locomotion could be regulated by multichannel modulations. This study provides insight into the ionic basis for control of motor output in walking. NEW & NOTEWORTHY Mammalian spinal motoneurons have their excitability adapted to facilitate recruitment and firing during locomotion. Cat lumbar motoneurons display dramatic changes in membrane properties during fictive locomotion. These changes lead to a varying alteration of frequency-current relationship. The mechanisms underlying the changes remain unknown. In particular, little is known about the ionic basis for regulation of motoneuronal excitability and thus control of the motor output for walking by the spinal motor system.

Tachykinin-mediated modulation of sensory neurons, interneurons, and synaptic transmission in the lamprey spinal cord

1996 ◽  
Vol 76 (6) ◽  
pp. 4031-4039 ◽  
Author(s):  
D. Parker ◽  
S. Grillner
Keyword(s):  
Spinal Cord ◽  
Substance P ◽  
Synaptic Transmission ◽  
Dorsal Root ◽  
Input Resistance ◽  
Dorsal Column ◽  
Giant Interneurons ◽  
Potassium Conductances ◽  
Dorsal Cells ◽  
Measurable Change

1. Tachykinin-like immunoreactivity is found in the dorsal roots, dorsal horn, and dorsal column of the lamprey. The effect of tachykinins on sensory processing was examined by recording intracellularly from primary sensory dorsal cells and second-order spinobulbar giant interneurons. Modulation of synaptic transmission was examined by making paired recordings from dorsal cells and giant interneurons, or by eliciting compound depolarizations in the giant interneurons by stimulating the dorsal root or dorsal column. 2. Bath application of tachykinins depolarized the dorsal cells. This effect was mimicked by stimulation of the dorsal root, suggesting that dorsal root afferents may be a source of endogenous tachykinin input to the spinal cord. The depolarization was reduced by removal of sodium or calcium from the Ringer, or when potassium conductances were blocked, and was not associated with a measurable change in input resistance. Dorsal root stimulation also caused a depolarization in the dorsal cells, and this effect and that of bath-applied substance P, was blocked by the tachykinin antagonist spantide. 3. The tachykinin substance P could reduce inward and outward rectification in the dorsal cells, the effect on outward rectification only being seen when potassium conductances were blocked by tetraethylammonium (TEA). 4. Substance P increased the excitability of the dorsal cells and giant interneurons, shown by the increased spiking in response to depolarizing current pulses. The increased excitability was blocked by the tachykinin antagonist spantide. 5. Substance P modulated the dorsal cell action potential, by increasing the spike duration and reducing the amplitude of the afterhyperpolarization. The spike amplitude was not consistently affected. 6. Stimulation of the dorsal column resulted in either depolarizing or hyperpolarizing potentials in the giant interneurons. The amplitude of the depolarization was increased by substance P, whereas the amplitude of the hyperpolarization was reduced. These effects occurred independently of a measurable change in postsynaptic input resistance, suggesting that the modulation occurred presynaptically. Paired recordings from dorsal cells and giant interneurons failed to reveal an effect of substance P on dorsal cell-evoked excitatory postsynaptic potentials (EPSPs), suggesting that the potentiation of the dorsal column-evoked depolarization was due to an effect on other axons in the dorsal column. Dorsal root-evoked potentials could also be increased in the presence of substance P, although this effect was less consistent than the effect on dorsal column stimulation. 7. These results suggest that tachykinins modulate sensory input to the lamprey spinal cord by increasing the excitability of primary afferents and second-order giant interneurons, and also by modulating synaptic transmission. Tachykinins may result in potentiation of local spinal reflexes and also modulation of descending reticulospinal inputs to the spinal locomotor network as a result of potentiation of spinobulbar inputs.

Serotonin Modulates Dendritic Calcium Influx in Commissural Interneurons in the Mouse Spinal Locomotor Network

2007 ◽  
Vol 98 (4) ◽  
pp. 2157-2167 ◽  
Author(s):  
Manuel Díaz-Ríos ◽  
Daniel A. Dombeck ◽  
Watt W. Webb ◽  
Ronald M. Harris-Warrick
Keyword(s):  
Spinal Cord ◽  
Voltage Clamp ◽  
Neuronal Excitability ◽  
Calcium Influx ◽  
Active Role ◽  
Calcium Currents ◽  
Detectable Effect ◽  
Lumbar Region ◽  
Fictive Locomotion ◽  
Voltage Dependent

Commissural interneurons (CINs) help to coordinate left–right alternating bursting activity during fictive locomotion in the neonatal mouse spinal cord. Serotonin (5-HT) plays an active role in the induction of fictive locomotion in the isolated spinal cord, but the cellular targets and mechanisms of its actions are relatively unknown. We investigated the possible role of serotonin in modifying dendritic calcium currents, using a combination of two-photon microscopy and patch-clamp recordings, in identified CINs in the upper lumbar region. Dendritic calcium responses to applied somatic voltage-clamp steps were measured using fluorescent calcium indicator imaging. Serotonin evoked significant reductions in voltage-dependent dendritic calcium influx in about 40% of the dendritic sites studied, with no detectable effect in the remaining sites. We also detected differential effects of serotonin in different dendritic sites of the same neuron; serotonin could decrease voltage-sensitive calcium influx at one site, with no effect at a nearby site. Voltage-clamp studies confirmed that serotonin reduces the voltage-dependent calcium current in CINs. Current-clamp experiments showed that the serotonin-evoked decreases in dendritic calcium influx were coupled with increases in neuronal excitability; we discuss possible mechanisms by which these two seemingly opposing results can be reconciled. This research demonstrates that dendritic calcium currents are targets of serotonin modulation in a group of spinal interneurons that are components of the mouse locomotor network.

scholarly journals Inhibition of L-type calcium-channel activity by thapsigargin and 2,5-t-butylhydroquinone, but not by cyclopiazonic acid

1994 ◽  
Vol 302 (1) ◽  
pp. 147-154 ◽  
Author(s):  
E J Nelson ◽  
C C R Li ◽  
R Bangalore ◽  
T Benson ◽  
R S Kass ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Cyclopiazonic Acid ◽  
Calcium Currents ◽  
Pituitary Cells ◽  
Channel Activity ◽  
Patch Clamp Technique ◽  
Channel Current ◽  
Low Concentrations ◽  
Ic50 Values

Thapsigargin (TG), 2,5-t-butylhydroquinone (tBHQ) and cyclopiazonic acid (CPA) all inhibit the initial Ca(2+)-response to thyrotropin-releasing hormone (TRH) by depleting intracellular Ca2+ pools sensitive to inositol 1,4,5-trisphosphate (IP3). Treatment of GH3 pituitary cells for 30 min with 5 nM TG, 500 nM tBHQ or 50 nM CPA completely eliminated the TRH-induced spike in intracellular free Ca2+ ([Ca2+]i). Higher concentrations of TG and tBHQ, but not CPA, were also found to inhibit strongly the activity of L-type calcium channels, as measured by the increase in [Ca2+]i or 45Ca2+ influx stimulated by depolarization. TG and tBHQ blocked high-K(+)-stimulated 45Ca2+ uptake, with IC50 values of 10 and 1 microM respectively. Maximal inhibition of L-channel activity was achieved 15-30 min after drug addition. Inhibition by tBHQ was reversible, whereas inhibition by TG was not. TG and CPA did not affect spontaneous [Ca2+]i oscillations when tested at concentrations adequate to deplete the IP3-sensitive Ca2+ pool. However, 20 microM TG and 10 microM tBHQ blocked [Ca2+]i oscillations completely. The effect of drugs on calcium currents was measured directly by using the patch-clamp technique. When added to the external bath, 10 microM CPA caused a sustained increase in the calcium-channel current amplitude over 8 min, 10 microM tBHQ caused a progressive inhibition, and 10 microM TG caused an enhancement followed by a sustained block of the calcium current over 8 min. In summary, CPA depletes IP3-sensitive Ca2+ stores and does not inhibit voltage-operated calcium channels. At sufficiently low concentrations, TG depletes IP3-sensitive stores without inhibiting L-channel activity, but, for tBHQ, inhibition of calcium channels occurs at concentrations close to those needed to block agonist mobilization of intracellular Ca2+.

The Spinal GABAergic System Is a Strong Modulator of Burst Frequency in the Lamprey Locomotor Network

2004 ◽  
Vol 92 (4) ◽  
pp. 2357-2367 ◽  
Author(s):  
David E. Schmitt ◽  
Russell H. Hill ◽  
Sten Grillner
Keyword(s):  
Spinal Cord ◽  
Detailed Analysis ◽  
Gabaergic Neurons ◽  
Ventral Root ◽  
Gabaergic System ◽  
Frequency Regulation ◽  
Fictive Locomotion ◽  
Burst Frequency ◽  
Pronounced Increase ◽  
Spinal Network

The spinal network coordinating locomotion is comprised of a core of glutamate and glycine interneurons. This network is modulated by several transmitter systems including spinal GABA interneurons. The purpose of this study is to explore the contribution of GABAergic neurons to the regulation of locomotor burst frequency in the lamprey model. Using gabazine, a competitive GABAA antagonist more specific than bicuculline, the goal was to provide a detailed analysis of the influence of an endogenous activation of GABAA receptors on fictive locomotion, as well as their possible interaction with GABAB and involvement of GABAC receptors. During N-methyl-d-aspartate (NMDA)-induced fictive locomotion (ventral root recordings in the isolated spinal cord), gabazine (0.1–100 μM) significantly increased the burst rate up to twofold, without changes in regularity or “burst quality.” Gabazine had a proportionately greater effect at higher initial burst rates. Picrotoxin (1–7.5 μM), a less selective GABAA antagonist, also produced a pronounced increase in frequency, but at higher concentrations, the rhythm deteriorated, likely due to the unspecific effects on glycine receptors. The selective GABAB antagonist CGP55845 also increased the frequency, and this effect was markedly enhanced when combined with the GABAA antagonist gabazine. The GABAC antagonist (1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid (TPMPA) had no effect on locomotor bursting. Thus the spinal GABA system does play a prominent role in burst frequency regulation in that it reduces the burst frequency by ≤50%, presumably due to presynaptic and soma-dendritic effects documented previously. It is not required for burst generation, but acts as a powerful modulator.

Changes in Electrophysiological Properties of Lamprey Spinal Motoneurons During Fictive Swimming

2002 ◽  
Vol 88 (5) ◽  
pp. 2463-2476 ◽  
Author(s):  
Michelle M. Martin
Keyword(s):  
Spinal Cord ◽  
Input Resistance ◽  
Spike Frequency ◽  
Calcium Currents ◽  
Quiescent State ◽  
Spike Frequency Adaptation ◽  
Free Solution ◽  
Spinal Motoneurons ◽  
Electrophysiological Properties ◽  
Frequency Adaptation

Electrophysiological properties of lamprey spinal motoneurons were measured to determine whether their cellular properties change as the spinal cord goes from a quiescent state to the active state of fictive swimming. Intracellular microelectrode recordings of membrane potential were made from motoneurons in the isolated spinal cord preparation. Electrophysiological properties were first characterized in the quiescent spinal cord, and then fictive swimming was induced by perfusion with d-glutamate and the measurements were repeated. During the depolarizing excitatory phase of fictive swimming, the motoneurons had significantly reduced rheobase and significantly increased input resistance compared with the quiescent state, with no significant changes in these parameters during the repolarizing inhibitory phase of swimming. Spike threshold did not change significantly during fictive swimming compared with the quiescent state. During fictive swimming, the slope of the spike frequency versus injected current ( F-I) relationship decreased significantly as did spike-frequency adaptation and the amplitude of the slow after-spike hyperpolarization (sAHP). Serotonin is known to be released endogenously from the spinal cord during fictive swimming and is known to reduce the amplitude of the sAHP. Therefore the effects of serotonin on cellular properties were tested in the quiescent spinal cord. It was found that, in addition to reducing the sAHP amplitude, serotonin also reduced the slope of the F-I relationship and reduced spike-frequency adaptation, reproducing the changes observed in these parameters during fictive swimming. Application of spiperone, a serotonin antagonist, significantly increased the sAHP amplitude during fictive swimming but had no significant effect on F-I slope or adaptation. Because serotonin may act in part through reduction of calcium currents, the effect of calcium-free solution (cobalt substituted for calcium) was tested in the quiescent spinal cord. Similar to fictive swimming and serotonin application, the calcium-free solution significantly reduced the sAHP amplitude, the slope of the F-I relationship, and spike-frequency adaptation. These results suggest that there are significant changes in the firing properties of motoneurons during fictive swimming compared with the quiescent state, and it is possible that these changes may be attributed in part to the endogenous release of serotonin acting via reduction of calcium currents.

scholarly journals Fast and Slow Locomotor Burst Generation in the Hemispinal Cord of the Lamprey

2003 ◽  
Vol 89 (6) ◽  
pp. 2931-2942 ◽  
Author(s):  
Lorenzo Cangiano ◽  
Sten Grillner
Keyword(s):  
Spinal Cord ◽  
Reciprocal Inhibition ◽  
Pattern Generation ◽  
Burst Activity ◽  
Burst Frequency ◽  
Glutamatergic Neurons ◽  
Voltage Dependent ◽  
Burst Pattern ◽  
Glycinergic Inhibition ◽  
Electrical Stimuli

A fundamental question in vertebrate locomotion is whether distinct spinal networks exist that are capable of generating rhythmic output for each group of muscle synergists. In many vertebrates including the lamprey, it has been claimed that burst activity depends on reciprocal inhibition between antagonists. This question was addressed in the isolated lamprey spinal cord in which the left and right sides of each myotome display rhythmic alternating activity. We sectioned the spinal cord along the midline and tested whether rhythmic motor activity could be induced in the hemicord with bath-applied d-glutamate or N-methyl-d-aspartate (NMDA) as in the intact spinal cord or by brief trains of electrical stimuli. Fast rhythmic bursting (2–12 Hz), coordinated across ventral roots, was observed with all three methods. Furthermore, to diminish gradually the crossed glycinergic inhibition, a progressive surgical lesioning of axons crossing the midline was implemented. This resulted in a gradual increase in burst frequency, linking firmly the fast hemicord rhythm [6.6 ± 1.7 (SD) Hz] to fictive swimming in the intact cord (2.4 ± 0.7 Hz). Ipsilateral glycinergic inhibition was not required for the hemicord burst pattern generation, suggesting that an interaction between excitatory glutamatergic neurons suffices to produce the unilateral burst pattern. In NMDA, burst activity at a much lower rate (0.1–0.4 Hz) was also encountered, which required the voltage-dependent properties of NMDA receptors in contrast to the fast rhythm. Swimming is thus produced by pairs of unilateral burst generating networks with reciprocal inhibitory connections that not only ensure left/right alternation but also downregulate frequency.

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