scholarly journals Alternating rhythmic activity induced by dorsal root stimulation in the neonatal rat spinal cord in vitro

2001 ◽  
Vol 530 (1) ◽  
pp. 105-112 ◽  
Author(s):  
Cristina Marchetti ◽  
Marco Beato ◽  
Andrea Nistri
Keyword(s):  
Spinal Cord ◽  
Dorsal Root ◽  
Rhythmic Activity ◽  
Neonatal Rat ◽  
Rat Spinal Cord ◽  
Root Stimulation

Neuronal Bursting Induced by NK3 Receptor Activation in the Neonatal Rat Spinal Cord In Vitro

2001 ◽  
Vol 86 (6) ◽  
pp. 2939-2950 ◽  
Author(s):  
Cristina Marchetti ◽  
Andrea Nistri
Keyword(s):  
Spinal Cord ◽  
Membrane Potential ◽  
Dorsal Root ◽  
Extracellular Recording ◽  
Rhythmic Activity ◽  
Input Resistance ◽  
Receptor Activation ◽  
Neonatal Rat ◽  
Rat Spinal Cord

Intracellular recording from lumbar motoneurons and extracellular recording from ventral roots of the neonatal rat isolated spinal cord were used to study the mechanisms responsible for the excitation mediated by NK3 tachykinin receptors. The selective NK3 agonists senktide or [MePhe7]neurokinin B induced a slow depolarization with superimposed oscillations (mean period ± SD was 2.8 ± 0.8 s) that, in the majority of cases, showed left-right alternation at segmental level and were synchronous between L2 and L5 of the same side. During agonist wash out (5–20 min) a delayed form of hyperexcitability emerged consisting of bursts lasting 8 ± 2 s (average interburst interval 55 ± 21 s) with superimposed oscillations usually with homosegmental alternation and heterosegmental synchronicity. Such bursting was accompanied by depression of GABAergic dorsal root potentials evoked by dorsal root stimulation and of the recurrent inhibitory postsynaptic potential recorded from motoneurons. Despite bursting, motoneuron membrane potential returned to baseline while input resistance was increased. Bursts were a network-dependent phenomenon triggered by previous NK3 receptor activation because bursting was suppressed by glutamate receptor antagonists and was insensitive to motoneuron membrane potential or subsequent application of an NK3 receptor antagonist. NK3 receptors operated synergistically with N-methyl-d-aspartate (NMDA) and 5-hydroxytryptamine (5-HT) to trigger fully alternating locomotor-like rhythms while NK3 receptor antagonism disrupted the same rhythm. In summary, in the neonatal rat spinal cord NK3 receptors could trigger rhythmic activity predominantly with alternation at segmental level but with synchronous coupling between ipsilateral motor pools. NK3receptor activation could also facilitate fictive locomotor patterns induced by NMDA and 5-HT.

Effects of inhibitory amino acid antagonists on reciprocal inhibitory interactions during rhythmic motor activity in the in vitro neonatal rat spinal cord

1995 ◽  
Vol 74 (3) ◽  
pp. 1109-1117 ◽  
Author(s):  
K. C. Cowley ◽  
B. J. Schmidt
Keyword(s):  
Spinal Cord ◽  
Motor Activity ◽  
Receptor Agonist ◽  
Gabab Receptor ◽  
Glycine Receptor ◽  
Rhythmic Activity ◽  
Neonatal Rat ◽  
Rat Spinal Cord ◽  
Rhythmic Motor

1. The role of inhibitory amino acid transmission in the coordination and generation of rhythmic motor activity was examined with the use of an in vitro neonatal rat spinal cord preparation. Before adding gamma-aminobutyric acid (GABA) or glycine receptor agonists and antagonists, rhythmic motor activity was induced by bath application of acetylcholine (ACh), N-methyl-D,L-aspartate (NMA), or serotonin (5-HT) while monitoring bilateral ankle flexor and extensor electroneurograms (ENGs). The timing of rhythmic flexor and extensor discharge was consistent with that seen during overground locomotion in 27% of 84 bath applications of these substances (n = 65 preparations). 2. Subsequent addition of the GABAA receptor agonist muscimol, the GABAB receptor agonist baclofen, or glycine, abolished rhythmic activity in 95% of the tested applications. 3. GABAB receptor blockade did not disrupt alternating patterns of ENG discharge. However, addition of the GABAA receptor antagonist bicuculline, or the glycine receptor antagonist strychnine, transformed alternating flexor-extensor and left-right activity into patterns characterized by bilaterally synchronous rhythmic activation of all hindlimb ENGs. The onset of individual ENG bursts was more abrupt following bicuculline or strychnine. Strychnine also synchronized high-frequency (4-8 Hz) packets of rhythmic discharge within ENG bursts. 4. Some preparations developed synchronous, but unstable, rhythmic activity in the presence of bicuculline or strychnine alone. However, NMA, 5-HT, or ACh was usually required in addition to these antagonists to promote sustained rhythmic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Regional Distribution of the Locomotor Pattern-Generating Network in the Neonatal Rat Spinal Cord

1997 ◽  
Vol 77 (1) ◽  
pp. 247-259 ◽  
Author(s):  
K. C. Cowley ◽  
B. J. Schmidt
Keyword(s):  
Spinal Cord ◽  
Regional Distribution ◽  
Rhythmic Activity ◽  
Neonatal Rat ◽  
Lumbar Region ◽  
Rat Spinal Cord ◽  
Locomotor Pattern ◽  
Thoracic Cord ◽  
Lumbar Cord

Cowley, K. C. and B. J. Schmidt. Regional distribution of the locomotor pattern-generating network in the neonatal rat spinal cord. J. Neurophysiol. 77: 247–259, 1997. The regional distribution of spinal cord networks producing locomotor-like, as well as non-locomotor-like, activity was studied with the use of an in vitro neonatal rat preparation. Rhythmic activity was induced by bath application of either serotonin (5-HT), acetylcholine (ACh), N-methyl-d,l-aspartate (NMA), or combined 5-HT/NMA, and was monitored via hindlimb flexor (peroneal) and extensor (tibial) electroneurograms (ENGs) or ventral root recordings. In some experiments, synchronous patterns were produced by the addition of inhibitory amino acid (IAA) receptor antagonists. Selective application of 5-HT to cervical and thoracic cord regions induced rhythmic activity in these segments but failed to evoke hindlimb ENG discharge. Exposure of the isolated lumbar region to 5-HT produced tonic activity only. Application of 5-HT to the whole cord produced locomotor-like activity in hindlimb ENGs that persisted after midsagittal section of the spinal cord from the conus to the thoracolumbar junction. In other experiments, transverse hemisection of the rostral lumbar cord during whole cord exposure to 5-HT abolished rhythmic activity in ipsilateral hindlimb ENGs, suggesting that under these conditions rhythmic activity on one side of the lumbar cord was insufficient to maintain rhythmic activity on the contralateral side. Selective application of NMA or ACh to cervical and/or thoracic cord regions evoked rhythmic activity in these supralumbar segments, as well as rhythmic, but non-locomotor-like, activity in the lumbar region. In contrast to the effect of 5-HT, both NMA and ACh evoked rhythmic activity when applied solely to the lumbar region, and the side-to-side alternation produced by whole cord ACh application was uncoupled by midsagittal lesions of the lumbar region. In the presence of IAA antagonists, the side-to-side coupling of bilaterally synchronous rhythms was maintained despite extensive midsagittal lesions leaving all but one or two segments of either cervical, thoracic, or lumbar cord bilaterally intact, and rhythmic activity could be maintained even in single isolated hemisegments. The effects of 5-HT/NMA were similar to those observed with the use of 5-HT alone, although 5-HT/NMA induced rhythmic activity in hindlimb ENGs when applied selectively to supralumbar regions. The results suggest that 1) a 5-HT-sensitive oscillatory network, capable of producing a locomotor-like pattern of activity, is distributed throughout the supralumbar region of the spinal cord and mediates descending rhythmic drive to lumbar motor centers; 2) NMA- and ACh-sensitive rhythmogenic elements are distributed throughout the spinal cord, including the lumbar region; and 3) the spinal cord contains an extensive propriospinal network of reciprocal inhibitory and excitatory connections characterized by redundantly organized side-to-side projections.

Depression of Windup of Spinal Neurons in the Neonatal Rat Spinal Cord In Vitro by an NK3 Tachykinin Receptor Antagonist

2001 ◽  
Vol 85 (4) ◽  
pp. 1502-1511 ◽  
Author(s):  
Mario Barbieri ◽  
Andrea Nistri
Keyword(s):  
Spinal Cord ◽  
Synaptic Transmission ◽  
Receptor Antagonist ◽  
Dorsal Root ◽  
Direct Action ◽  
Extracellular Recording ◽  
Neonatal Rat ◽  
Rat Spinal Cord ◽  
Tachykinin Receptor

The effects of the NK3 tachykinin receptor antagonist SR 142801 on synaptic transmission and spike windup induced by trains of stimuli applied to a dorsal root were investigated with intra- and extracellular recording from the neonatal rat spinal cord in vitro. SR 142801 (10 μM) reduced the depolarization (recorded from lumbar ventral roots) induced by senktide (an NK3 agonist) more strongly than the one evoked by substance P methyl ester (SPMeO; an NK1 agonist). Nevertheless, after a long (>2 h) application time, SR 142801 largely depressed the response to SPMeO as well. When NK1 or NK3 receptors were blocked by >50% in the presence of SR 142801, there was also a significant reduction in the cumulative depolarization induced by repeated stimuli to a single dorsal root. This blocking action by SR 142801 was also observed in the presence of the N-methyl-d-aspartate (NMDA) receptor antagonist d-aminophosphonovalerate (APV) and the calcium channel blocker nifedipine. Intracellular data from lumbar motoneurons showed that the spike windup was the first and most sensitive target for the SR 142801 blocking effect. Increasing stimulus strength to dorsal root fibers could partly surmount such a block. SR 142801 per se had no direct action on fast synaptic transmission, membrane potential, or input resistance. These findings indicate that SR 142801 could lead to an early, large reduction in the windup of action potential discharge by motoneurons, suggesting its ability to suppress the reflex component of central sensitization evoked by repeated dorsal root stimuli.

Whole Cell Recordings of Lumbar Motoneurons During Locomotor-Like Activity in the In Vitro Neonatal Rat Spinal Cord

1998 ◽  
Vol 79 (2) ◽  
pp. 743-752 ◽  
Author(s):  
S. Hochman ◽  
B. J. Schmidt
Keyword(s):  
Spinal Cord ◽  
Membrane Potential ◽  
Rhythmic Activity ◽  
Input Resistance ◽  
Membrane Depolarization ◽  
Neonatal Rat ◽  
Rat Spinal Cord ◽  
Whole Cell ◽  
Whole Cell Recordings

Hochman, S. and B. J. Schmidt. Whole cell recordings of lumbar motoneurons during locomotor-like activity in the in vitro neonatal rat spinal cord. J. Neurophysiol. 79: 743–752, 1998. Whole cell current- and voltage-clamp recordings were obtained from lumbar motoneurons in the isolated neonatal rat spinal cord to characterize the behavior of motoneurons during neurochemically induced locomotor-like activity. Bath application of serotonin (10–100 μM) in combination with N-methyl-d-aspartate (1–12 μM) initially produced tonic membrane depolarization (mean = 26 mV), increased input resistance, decreased rheobase, and increased spike inactivation in response to depolarizing current pulse injections. After the initial tonic depolarization, rhythmic fluctuations of the motoneuron membrane potential (locomotor drive potentials; LDPs) developed that were modulated phasically in association with ventral root discharge. The peak and trough voltage levels of the LDP fluctuated above and below the membrane potential recorded immediately before the onset of rhythmic activity. Similarly, firing frequency was modulated above and below prelocomotion firing rates (in those motoneurons that displayed neurochemically induced tonic firing immediately before the onset of rhythmic activity). These observations are consistent with an alternation between phasic excitatory and inhibitory synaptic drives. The amplitude of LDPs and rhythmic excitatory drive current increased with membrane depolarization from −80 to −40 mV and then decreased with further depolarization, thus displaying nonlinear voltage-dependence. Faster frequency, small amplitude voltage fluctuations were observed superimposed on the depolarized phase of LDPs. In some motoneurons, the trajectory of these superimposed fluctuations was consistent with a synaptic origin, whereas in other cells, the regular sinusoidal appearance of the fluctuations and the occurrence of superimposed plateau potentials were more compatible with the activation of an intrinsic membrane property. One motoneuron displayed exclusively excitatory phasic drive, and another motoneuron was characterized by inhibitory phasic drive alone, during rhythmic activity. These findings are compatible with the concept of a central pattern generator that is capable of delivering both excitatory and inhibitory drive to motoneurons during locomotion. The data also suggest that the rhythmic excitatory and inhibitory outputs of the hypothetical half-center model can be dissociated and operate in isolation.

The in vitro neonatal rat spinal cord preparation: a new insight into mammalian locomotor mechanisms

2004 ◽  
Vol 190 (5) ◽  
pp. 343-357 ◽  
Author(s):  
F. Clarac ◽  
E. Pearlstein ◽  
J. F. Pflieger ◽  
L. Vinay
Keyword(s):  
Spinal Cord ◽  
Neonatal Rat ◽  
Rat Spinal Cord ◽  
Insight Into

Small-caliber afferent inputs produce a heterosynaptic facilitation of the synaptic responses evoked by primary afferent A-fibers in the neonatal rat spinal cord in vitro

1993 ◽  
Vol 69 (6) ◽  
pp. 2116-2128 ◽  
Author(s):  
S. W. Thompson ◽  
C. J. Woolf ◽  
L. G. Sivilotti
Keyword(s):  
Spinal Cord ◽  
Dorsal Root ◽  
Fiber Strength ◽  
Conditioning Stimulus ◽  
Neonatal Rat ◽  
Primary Afferent ◽  
Synaptic Potentials ◽  
C Fiber ◽  
Afferent Inputs

1. The effect of brief primary afferent inputs on the amplitude and duration of the synaptic potentials evoked in ventral horn (VH) neurons by the activation of other unconditioned primary afferents was studied by current-clamp intracellular recording in the neonatal rat hemisected spinal cord in vitro. Low-frequency (1 Hz) trains of stimulation were applied to a lumbar dorsal root (Conditioning root) for 20-30 s. Test excitatory synaptic potentials (EPSPs) were evoked by single electrical shocks applied to an adjacent Test dorsal root. 2. Test and Conditioning inputs were generated at stimulation strengths sufficient to activate A beta-, A delta- and C-afferent fibers successively. At A delta- and C-fiber strength the EPSPs lasted for 4-6 s, and, during the repetitive Conditioning inputs, these summated to produce a progressively incrementing cumulative depolarization that slowly decayed back to the control Vm over tens of seconds. 3. Dorsal root conditioning produced heterosynaptic facilitation, defined as an enhancement of Test EPSPs above their DC matched controls, in 7 out of 20 neurons. To facilitate the unconditioned afferent input, the intensity of conditioning stimulation had to exceed the threshold for the activation of thin myelinated (A delta) afferents: conditioning at A beta-fiber strength had no effect, whereas A delta- and C-fiber strength conditioning were equally effective. 4. Heterosynaptic facilitation of only A beta- or A delta-fiber-evoked Test EPSPs was observed, no enhancement of C-fiber strength Test EPSPs could be demonstrated. The facilitation manifested as increases in the EPSP peak amplitude, area or the number of action potentials evoked. 5. Conditioning trials that produced heterosynaptic facilitation generated cumulative depolarizations larger than those produced by ineffective conditioning trials (9.1 +/- 3.1 vs. 3.3 +/- 0.5 mV after 20 s conditioning at resting Vm, mean +/- SE, n = 6 and 13, respectively; P < 0.05). The slope of the Vm trajectory during the summation of the conditioning EPSPs was higher in trials resulting in heterosynaptic facilitation, at 0.31 +/- 0.10 mV/s in neurons with heterosynaptic facilitation and 0.06 +/- 0.02 mV/s in cells without heterosynaptic facilitation (P < 0.05). 5. Four of the 20 VH neurons in our sample responded to A delta/C-fiber conditioning with action-potential windup: all 4 also displayed heterosynaptic facilitation. 6. Heterosynaptic facilitation decayed after the completion of the conditioning stimulus with a time course that was parallel to but not superimposable on that of the slow Vm depolarization evoked by the conditioning.(ABSTRACT TRUNCATED AT 400 WORDS)

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