5-HT Modulation of Identified Segmental Premotor Interneurons in the Lamprey Spinal Cord

2006 ◽  
Vol 96 (2) ◽  
pp. 931-935 ◽  
Author(s):  
Zoltán Biró ◽  
Russell H. Hill ◽  
Sten Grillner
Keyword(s):  
Spinal Cord ◽  
Synaptic Transmission ◽  
Membrane Properties ◽  
Frequency Regulation ◽  
Inhibitory Interneurons ◽  
Fictive Locomotion ◽  
Locomotor Rhythm ◽  
Swimming Pattern ◽  
Electrical Component ◽  
Types Of Interneurons

Ipsilaterally projecting spinal excitatory interneurons (EINs) generate the hemisegmental rhythmic locomotor activity in lamprey, while the commissural interneurons ensure proper left-right alternation. 5-HT is a potent modulator of the locomotor rhythm and is endogenously released from the spinal cord during fictive locomotion. The effect of 5-HT was investigated for three segmental premotor interneuron types: EINs, commissural excitatory and commissural inhibitory interneurons. All three types of interneurons produced chemical postsynaptic potentials in motoneurons, but only those from EINs had an electrical component. The effect of 5-HT was studied on the slow afterhyperpolarization, involved in spike frequency regulation, and on the segmental synaptic transmission to motoneurons. 5-HT induced a reduction in the slow afterhyperpolarization and a depression of synaptic transmission in all three types of segmental interneurons. Thus 5-HT is a very potent modulator of membrane properties and synaptic transmission of last-order segmental premotor interneurons. Such modulation of locomotor network interneurons can partially account for the observed effects of 5-HT on the swimming pattern in lamprey.

Quantitative Investigation of Calcium Signals for Locomotor Pattern Generation in the Lamprey Spinal Cord

2004 ◽  
Vol 92 (3) ◽  
pp. 1796-1806 ◽  
Author(s):  
Gonzalo Viana Di Prisco ◽  
Simon Alford
Keyword(s):  
Spinal Cord ◽  
Ventral Horn ◽  
Pattern Generation ◽  
Membrane Properties ◽  
Fictive Locomotion ◽  
Locomotor Rhythm ◽  
Locomotor Pattern ◽  
Network Coordination ◽  
Neuronal Oscillators ◽  
Intrinsic Membrane Properties

Locomotor pattern generation requires the network coordination of spinal ventral horn neurons acting in concert with the oscillatory properties of individual neurons. In the spinal cord, N-methyl-d-aspartate (NMDA) activates neuronal oscillators that are believed to rely on Ca2+ entry to the cytosol through voltage-operated Ca2+ channels and synaptically activated NMDA receptors. Ca2+ signaling in lamprey ventral horn neurons thus plays a determinant role in the regulation of the intrinsic membrane properties and network synaptic interaction generating spinal locomotor neural pattern activity. We have characterized aspects of this signaling quantitatively for the first time. Resting Ca2+ concentrations were between 87 and 120 nM. Ca2+ concentration measured during fictive locomotion increased from soma to distal dendrites [from 208 ± 27 (SE) nM in the soma to 335 ± 41 nM in the proximal dendrites to 457 ± 68 nM in the distal dendrites]. We sought to determine the temporal and spatial properties of Ca2+ oscillations, imaged with Ca2+-sensitive dyes and correlated with fluctuations in membrane potential, during lamprey fictive locomotion. The Ca2+ signals recorded in the dendrites showed a great deal of spatial heterogeneity. Rapid changes in Ca2+-induced fluorescence coincided with action potentials, which initiated significant Ca2+ transients distributed throughout the neurons. Ca2+ entry to the cytosol coincided with the depolarizing phase of the locomotor rhythm. During fictive locomotion, larger Ca2+ oscillations were recorded in dendrites compared with somata in motoneurons and premotor interneurons. Ca2+ fluctuations were barely detected with dyes of lower affinity providing alternative empirical evidence that Ca2+ responses are limited to hundreds of nanomolars during fictive locomotion.

Tonic and phasic synaptic input to spinal cord motoneurons during fictive locomotion in frog embryos

1982 ◽  
Vol 48 (6) ◽  
pp. 1279-1288 ◽  
Author(s):  
S. R. Soffe ◽  
A. Roberts
Keyword(s):  
Spinal Cord ◽  
Synaptic Input ◽  
Inhibitory Interneurons ◽  
Fictive Locomotion ◽  
Inhibitory Pathway ◽  
Intact Side ◽  
Rhythmic Motor ◽  
Postsynaptic Potential ◽  
Late Developmental Stage ◽  
Motor Root

1. In curarized, late developmental stage Xenopus embryos, episodes of rhythmic motor root discharge, termed fictive swimming (17), may be evoked by touch or by dimming the lights, as in unparalyzed animals. Motoneurons are tonically depolarized throughout each episode, are phasically excited to fire 1 spike per cycle, and receive a midcycle inhibitory postsynaptic potential (IPSP) in phase with motor root activity on the opposite side. 2. Rostral hemisection of the spinal cord abolishes motor root discharge on the operated side caudal to the cut but leaves activity on the intact side unaffected. In motoneurons, the tonic depolarization is abolished on the hemisected side but is still present on the intact side. This is evidence that the tonic depolarization is a descending drive. 3. Midcycle IPSPs normally seen in motoneurons during fictive swimming are abolished by rostral hemisection of the opposite side of the cord but are still recorded on the cut side. The simplest conclusion is that the inhibitory interneurons responsible lie on the opposite side of the spinal cord to the motoneurons they inhibit, and so represent a reciprocal inhibitory pathway. 4. The phasic excitatory postsynaptic potentials (EPSPs), which drive motoneuron spikes during swimming, are still present on the intact side of a rostrally hemisected cord but are abolished on the operated side. We conclude that the excitatory interneurons responsible lie on the same side of the cord as the motoneurons they excite.

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.

Activity of medullary reticulospinal neurons during fictive locomotion

1993 ◽  
Vol 69 (6) ◽  
pp. 2232-2247 ◽  
Author(s):  
M. C. Perreault ◽  
T. Drew ◽  
S. Rossignol
Keyword(s):  
Spinal Cord ◽  
Reticular Formation ◽  
Firing Frequency ◽  
Lumbar Spinal Cord ◽  
Fictive Locomotion ◽  
Nerve Activity ◽  
Locomotor Rhythm ◽  
Reticulospinal Neurons ◽  
Lumbar Spinal ◽  
Temporally Correlated

1. The pattern of discharge of medullary reticulospinal neurons, identified by antidromic stimulation applied at the L1-L2 segment of the spinal cord, was studied during fictive locomotion, occurring spontaneously, or evoked by stimulation of the mesencephalic locomotor region in high-decerebrate, paralyzed cats. Unitary recordings were made in the medial reticular formation (P5.0-14.0 mm; L0.5-2.0 mm), and the fictive locomotor pattern was monitored by recording the electroneurogram (ENG) of representative flexor and extensor muscle nerves from each of the four limbs. 2. In total, 117 reticulospinal neurons were recorded in 15 cats. Among these, 73.5% (86/117) modified their discharge at the onset of locomotion. These cells were divided into three subpopulations: 34/86 of the cells always maintained a fixed temporal relationship with the activity of one of the recorded nerves (ENG-related = 39.6%); the pattern of discharge of 42/86 cells was related to the locomotor rhythm [(LR-related-48%)] but was not temporally correlated with any of the recorded nerves; and the remaining 10 cells increased their firing frequency at the onset of locomotion but remained tonic (TONIC-11.6%). 3. Of the ENG-related neurons, 64.8% were temporally correlated to extensor nerve activity, whereas the remaining 35.2% were correlated to flexor nerves. These neurons were either related to forelimb (55.9%) or hindlimb (44.1%) nerves lying either ipsilateral (38.2%) or contralateral (61.8%) to the recording site. A few neurons (n = 3; 8.8%) were related to nerve activity of more than one limb. 4. The pattern of discharge of the LR-related neurons, although not correlated to the activity of any one recorded nerve, could be preferentially related to the locomotor rhythm in either the forelimbs (12/23) or hindlimbs (11/23). 5. ENG- and LR-related reticulospinal neurons were intermingled in the medial reticular formation. In both cases, cells related to the forelimbs were located more dorsally than those related to the hindlimbs. It is suggested that both the ENG- and LR-related neurons represent a single functional population of reticulospinal neurons that is part of an intrinsically organized reticulospinal system that functions to coordinate the activity of the skeletal musculature. 6. The present results show that the majority of reticular neurons projecting as far as the lumbar spinal cord are phasically modulated during locomotion, even in the absence of phasic peripheral afferent inputs. Moreover, the complexity of the discharge patterns in paralyzed animals was found to be similar to that observed in the intact cat.(ABSTRACT TRUNCATED AT 400 WORDS)

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

Is NMDA Receptor Activation Essential for the Production of Locomotor-Like Activity in the Neonatal Rat Spinal Cord?

2005 ◽  
Vol 94 (6) ◽  
pp. 3805-3814 ◽  
Author(s):  
Kristine C. Cowley ◽  
Eugene Zaporozhets ◽  
Jason N. MacLean ◽  
Brian J. Schmidt
Keyword(s):  
Spinal Cord ◽  
Nmda Receptor ◽  
Receptor Activation ◽  
Neonatal Rat ◽  
Membrane Properties ◽  
Rat Spinal Cord ◽  
Locomotor Rhythm ◽  
Active Membrane ◽  
Nmda Receptor Activation

Previous work has established that in vitro bath application of N-methyl-d-aspartic acid (NMDA) promotes locomotor activity in a variety of vertebrate preparations including the neonatal rat spinal cord. In addition, NMDA receptor activation gives rise to active membrane properties that are postulated to contribute to the generation or stabilization of locomotor rhythm. However, earlier studies yielded conflicting evidence as to whether NMDA receptors are essential in this role. Therefore in this study, we examined the effect of NMDA receptor blockade, using d-2-amino-5-phosphono-valeric acid (AP5), on locomotor-like activity in the in vitro neonatal rat spinal cord. Locomotor-like activity was induced using 5-hydroxytryptamine (5-HT), acetylcholine, combined 5-HT and NMDA receptor activation, increased K+ concentration, or electrical stimulation of the brain stem and monitored using suction electrode recordings of left and right lumbar ventral root discharge. We also studied the effect on locomotor capacity of selectively suppressing NMDA receptor–mediated active membrane properties; this was achieved by removing Mg2+ ions from the bath, which in turn abolishes voltage-sensitive blockade of the NMDA receptor channel. The results show that, although NMDA receptor activation may seem essential for locomotor network operation under some experimental conditions, locomotor-like rhythms can nevertheless be generated in the presence of AP5 if spinal cord circuitry is exposed to appropriate levels of non–NMDA receptor–dependent excitation. Therefore neither NMDA receptor–mediated nonlinear membrane properties nor NMDA receptor activation in general is universally essential for locomotor network activation in the in vitro neonatal rat spinal cord.

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 Functional characterization of dI6 interneurons in the neonatal mouse spinal cord

2012 ◽  
Vol 107 (12) ◽  
pp. 3256-3266 ◽  
Author(s):  
Jason Dyck ◽  
Guillermo M. Lanuza ◽  
Simon Gosgnach
Keyword(s):  
Spinal Cord ◽  
Action Potentials ◽  
Neural Control ◽  
Motor Behavior ◽  
Functional Characterization ◽  
Rhythmic Activity ◽  
Ventral Root ◽  
Membrane Properties ◽  
Fictive Locomotion ◽  
Transgenic Mouse Line

Our understanding of the neural control of locomotion has been greatly enhanced by the ability to identify and manipulate genetically defined populations of interneurons that comprise the locomotor central pattern generator (CPG). To date, the dI6 interneurons are one of the few populations that settle in the ventral region of the postnatal spinal cord that have not been investigated. In the present study, we utilized a novel transgenic mouse line to electrophysiologically characterize dI6 interneurons located close to the central canal and study their function during fictive locomotion. The majority of dI6 cells investigated were found to be rhythmically active during fictive locomotion and could be divided into two electrophysiologically distinct populations of interneurons. The first population fired rhythmic trains of action potentials that were loosely coupled to ventral root output and contained several intrinsic membrane properties of rhythm-generating neurons, raising the possibility that these cells may be involved in the generation of rhythmic activity in the locomotor CPG. The second population fired rhythmic trains of action potentials that were tightly coupled to ventral root output and lacked intrinsic oscillatory mechanisms, indicating that these neurons may be driven by a rhythm-generating network. Together these results indicate that dI6 neurons comprise an important component of the locomotor CPG that participate in multiple facets of motor behavior.

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