GABA-Receptor–Independent Dorsal Root Afferents Depolarization in the Neonatal Rat Spinal Cord

1998 ◽  
Vol 79 (5) ◽  
pp. 2581-2592 ◽  
Author(s):  
E. Kremer ◽  
A. Lev-Tov
Keyword(s):  
Spinal Cord ◽  
Dorsal Root ◽  
Gaba Receptor ◽  
Neonatal Rat ◽  
Extracellular Potassium ◽  
Rat Spinal Cord ◽  
Extracellular Potassium Concentration ◽  
Dorsal Roots ◽  
Intact Brain ◽  
Dorsal Root Afferents

Kremer, E. and A. Lev-Tov. GABA-receptor–independent dorsal root afferents depolarization in the neonatal rat spinal cord. J. Neurophysiol. 79: 2581–2592, 1998. Dorsal root afferent depolarization and antidromic firing were studied in isolated spinal cords of neonatal rats. Spontaneous firing accompanied by occasional bursts could be recorded from most dorsal roots in the majority of the cords. The afferent bursts were enhanced after elevation of the extracellular potassium concentration ([K+]e) by 1–2 mM. More substantial afferent bursts were produced when the cords were isolated with intact brain stems. Rhythmic afferent bursts could be recorded from dorsal roots in some of the cords during motor rhythm induced by bath-applied serotonin and N-methyl-d-aspartate (NMDA). Bilaterally synchronous afferent bursts were produced in pairs of dorsal roots after replacing the NaCl in the perfusate with sodium-2-hydroxyethansulfonate or after application of the γ-aminobutyric acid-A (GABAA) receptor antagonist bicuculline with or without serotonin (5-HT) and NMDA. Antidromic afferent bursts also could be elicited under these conditions by stimulation of adjacent dorsal roots, ventrolateral funiculus axons, or ventral white commissural (VWC) fibers. The antidromic bursts were superimposed on prolonged dorsal root potentials (DRPs) and accompanied by a prolonged increase in intraspinal afferent excitability. Surgical manipulations of the cord revealed that afferent firing in the presence of bicuculline persisted in the hemicords after hemisection and still was observed after removal of their ventral horns. Cutting the VWC throughout its length did not perturb the bilateral synchronicity of the discharge. These findings suggest that the activity of dorsal horn neurons is sufficient to produce the discharge and that the bilateral synchronicity can be maintained by cross connectivity that is relayed from side to side dorsal to the VWC. Antagonists of GABAB, 5-HT2/5-HT1C, or glutamate metabotropic group II and III receptors could not abolish afferent depolarization in the presence of bicuculline. Depolarization comparable in amplitude to DRPs, could be produced in tetrodotoxin-treated cords by elevation of [K+]e to the levels reported to develop in the neonatal rat spinal cord in response to dorsal root stimulation. A mechanism involving potassium transients produced by neuronal activity therefore is suggested to be the major cause of the GABA-independent afferent depolarization reported in our study. Possible implications of potassium transients in the developing and the adult mammalian spinal cord are discussed.

Modulation of monosynaptic excitation in the neonatal rat spinal cord

1993 ◽  
Vol 70 (3) ◽  
pp. 1151-1158 ◽  
Author(s):  
M. Pinco ◽  
A. Lev-Tov
Keyword(s):  
Spinal Cord ◽  
Dorsal Root ◽  
Neonatal Rat ◽  
Bathing Solution ◽  
Duration Stimulus ◽  
Low Calcium ◽  
Dorsal Root Afferents ◽  
Stimulation Of ◽  
Monosynaptic Excitation

1. The effects of high-frequency (5-50 Hz) stimulation of dorsal root afferents on monosynaptic excitation of alpha motoneurons was studied in the in vitro spinal cord preparation of the neonatal rat, using sharp-electrode intracellular recordings. 2. Double pulse stimulation of dorsal root afferents induced severe depression of testing excitatory postsynaptic potentials (EPSPs) at each of the tested interstimulus intervals (15 ms-5 s). After perfusion of the preparation with low-calcium, high-magnesium Krebs saline, the amplitude of the conditioning EPSPs was markedly decreased and the testing EPSPs exhibited substantial facilitation that was maximal at the 20-ms interval and that was accompanied by depression at intervals > or = 60-100 ms. 3. Short-duration stimulus trains applied to dorsal root afferents normally induced tetanic depression of the intracellularly recorded monosynaptic EPSPs. Switching the bathing solution to low-calcium, high-magnesium saline decreased the control EPSP and induced facilitation and then tetanic potentiation (TP) of the EPSPs within the applied train. The magnitude of potentiation (% potentiation) of these EPSPs depended on the interpulse interval of the short stimulus train and on the degree of attenuation of the unpotentiated control EPSP after the solution was changed from normal- to low-calcium Krebs solution. 4. Long-duration stimulus trains applied to dorsal root afferents at 5-10 Hz induced marked depression of monosynaptic EPSPs during the train. The depression was alleviated after cessation of the tetanic stimulation and was followed in some cases by slight posttetanic potentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Spatiotemporal Patterns of Dorsal Root–Evoked Network Activity in the Neonatal Rat Spinal Cord: Optical and Intracellular Recordings

2005 ◽  
Vol 94 (3) ◽  
pp. 1952-1961 ◽  
Author(s):  
Lea Ziskind-Conhaim ◽  
Stephen Redman
Keyword(s):  
Spinal Cord ◽  
Action Potentials ◽  
Dorsal Root ◽  
Spatiotemporal Patterns ◽  
Neonatal Rat ◽  
Network Activity ◽  
Rat Spinal Cord ◽  
Optical Signals ◽  
Postsynaptic Potentials ◽  
Neuronal Ensembles

Spatiotemporal patterns of dorsal root–evoked potentials were studied in transverse slices of the rat spinal cord by monitoring optical signals from a voltage-sensitive dye with multiple-photodiode optic camera. Typically, dorsal root stimulation generated two basic waveforms of voltage images: dual-component images consisting of fast, spike-like signal followed by a slow signal in the dorsal horn, and small, slow signals in the ventral horn. To qualitatively relate the optical signals to membrane potentials, whole cell recordings were combined with measurements of light absorption in the area around the soma. The slow optical signals correlated closely with subthreshold postsynaptic potentials in all regions of the cord. The spike-like component was not associated with postsynaptic action potentials, suggesting that the fast signal was generated by presynaptic action potentials. Firing in a single neuron could not be detected optically, implying that local voltage images originated from synchronously activated neuronal ensembles. Blocking glutamatergic synaptic transmission inhibited excitatory postsynaptic potentials (EPSPs) and significantly reduced the slow optical signals, indicating that they were mediated by glutamatergic synapses. Suppressing glycine-mediated inhibition increased the amplitude of both optical signals and EPSPs, while blocking GABAA receptor–mediated synapses, increased the amplitude and time course of EPSPs and prolonged the duration of voltage images in larger areas of the slice. The close correlation between evoked EPSPs and their respective local voltage images shows the advantage of the high temporal resolution optical system in measuring both the spatiotemporal dynamics of segmental network excitation and integrated potentials of neuronal ensembles at identified sites.

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.

Synaptic excitation of alpha-motoneurons by dorsal root afferents in the neonatal rat spinal cord

1993 ◽  
Vol 70 (1) ◽  
pp. 406-417 ◽  
Author(s):  
M. Pinco ◽  
A. Lev-Tov
Keyword(s):  
Spinal Cord ◽  
Nmda Receptor ◽  
Dorsal Root ◽  
Repetitive Stimulation ◽  
Neonatal Rat ◽  
Receptor Blocker ◽  
Epsp Amplitude ◽  
Nmda Receptor Blocker ◽  
Dorsal Root Afferents ◽  
Stimulation Of

1. Excitatory synaptic transmission in mono- and polysynaptic pathways between dorsal root afferents and alpha-motoneurons was studied in the spinal cord preparation of the neonatal rat isolated in vitro, using sharp-electrode intracellular recordings. 2. The duration of monosynaptic excitatory postsynaptic potentials (EPSPs) elicited in lumbar motoneurons were shortened after addition of the specific N-methyl-D-aspartate (NMDA) receptor blocker 2-amino-5-phosphonovaleric acid (APV) to the perfusate. The EPSPs were then completely blocked by the non-NMDA receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). 3. A robust NMDA-receptor-mediated component of monosynaptic EPSPs was revealed by addition of CNQX to the bathing medium. This component reached as much as 30% of the EPSP amplitude, was evident at resting potential level in both low and normal Mg2+ Krebs saline, and could be completely abolished by addition of APV. These findings suggest that the NMDA-receptor-mediated component may contribute to monosynaptic excitation under normal conditions. 4. Polysynaptic EPSPs evoked in motoneurons in the fifth lumbar segment by stimulation of the fourth lumbar dorsal root in the presence of the glycine and gamma-aminobutyric acid A (GABAA) receptor blockers strychnine and bicuculline could be completely or partially blocked by application of either APV or CNQX. Suprathreshold activity could be then elicited in these motoneurons by increasing the stimulation intensity by a factor of 2 to 3. A complete blockade of polysynaptic excitation at these stimulation intensities was obtained only in the presence of both APV and CNQX. These results suggest that both receptor subtypes make a significant contribution to polysynaptic excitation of alpha-motoneurons by dorsal root afferents. 5. Analysis of variation in the amplitudes of the non-NMDA-receptor-mediated component of the monosynaptic EPSP and of the estimated (occurring 25 ms after the EPSP initiation) and the pharmacologically resolved NMDA component was done during low-frequency repetitive stimulation of the dorsal root. The kinetics of the initial decrease in EPSP amplitude during repetitive stimulation and the dependence of the EPSP amplitude on the stimulation frequency was similar for the NMDA- and non-NMDA-receptor-mediated components of the EPSPs. Addition of the GABAB receptor agonist L-(-) baclofen to the perfusate decreased the EPSP amplitude and reduced the frequency-dependent synaptic depression of both the NMDA- and non-NMDA-receptor-mediated components of monosynaptic EPSPs to the same level.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

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