Differential Effects of Opioids on Sacrocaudal Afferent Pathways and Central Pattern Generators in the Neonatal Rat Spinal Cord

2007 ◽  
Vol 97 (4) ◽  
pp. 2875-2886 ◽  
Author(s):  
D. Blivis ◽  
G. Z. Mentis ◽  
M. J. O'Donovan ◽  
A. Lev-Tov
Keyword(s):  
Spinal Cord ◽  
Opioid Receptor ◽  
Central Pattern Generators ◽  
Rhythmic Activity ◽  
Ventral Horn ◽  
Neonatal Rat ◽  
Experimental Chamber ◽  
Afferent Pathways ◽  
Anatomical Basis ◽  
Ventromedial Medulla

The effects of opioids on sacrocaudal afferent (SCA) pathways and the pattern-generating circuitry of the thoracolumbar and sacrocaudal segments of the spinal cord were studied in isolated spinal cord and brain stem-spinal cord preparations of the neonatal rat. The locomotor and tail moving rhythm produced by activation of nociceptive and nonnociceptive sacrocaudal afferents was completely blocked by specific application of the μ-opioid receptor agonist [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin acetate salt (DAMGO) to the sacrocaudal but not the thoracolumbar segments of the spinal cord. The rhythmic activity could be restored after addition of the opioid receptor antagonist naloxone to the experimental chamber. The opioid block of the SCA-induced rhythm is not due to impaired rhythmogenic capacity of the spinal cord because a robust rhythmic activity could be initiated in the thoracolumbar and sacrocaudal segments in the presence of DAMGO, either by stimulation of the ventromedial medulla or by bath application of N-methyl-d-aspartate/serotonin. We suggest that the opioid block of the SCA-induced rhythm involves suppression of synaptic transmission through sacrocaudal interneurons interposed between SCA and the pattern-generating circuitry. The expression of μ opioid receptors in several groups of dorsal, intermediate and ventral horn interneurons in the sacrocaudal segments of the cord, documented in this study, provides an anatomical basis for this suggestion.

Spatiotemporal characteristics of 5-HT and dopamine-induced rhythmic hindlimb activity in the in vitro neonatal rat

1996 ◽  
Vol 75 (4) ◽  
pp. 1472-1482 ◽  
Author(s):  
O. Kiehn ◽  
O. Kjaerulff
Keyword(s):  
Muscle Activity ◽  
Central Pattern Generators ◽  
Rhythmic Activity ◽  
Biceps Femoris ◽  
Ventral Root ◽  
Neonatal Rat ◽  
Cycle Duration ◽  
Spatiotemporal Characteristics ◽  
The Relationship

1. Rhythmic activity was induced with either serotonin (5-HT; 10-100 microM) or dopamine (0.1-1.0 mM), in the in vitro spinal cord preparation of neonatal rats, with one intact hindlimb attached. Patterns of activity were investigated with multiple EMG recordings and the spatiotemporal characteristics of 5-HT- and dopamine-induced activity compared. 2. Dopamine-induced rhythmic activity was slow (cycle duration: 2.2-70.1 s) and irregular, whereas rhythmic activity induced by 5-HT was fast (cycle duration: 1.3-5.1 s) and regular. 3. During 5-HT- and dopamine-induced rhythmic activity, the timing of muscular activity was similar for hip flexors and hip adductors, for semimembranosus (hip extensor), and for muscles controlling the ankle and the foot. 4. In contrast, notable differences in the phase in the pattern induced by 5-HT compared with that induced by dopamine were found in the biceps femoris, semitendinosus, and quadriceps muscles. Biceps femoris and semitendinosus (functional hip extensors and knee flexors) were always extensor-like during 5-HT-induced activity, whereas in dopamine, these muscles displayed flexor-like bursts and double bursts as well as extensor-like bursts. Lack of EMG activity in biceps femoris and semitendinosus was encountered also in dopamine. In rectus femoris, vastus lateralis, and vastus medialis (main function: knee extension), the activity was dominated by flexor-like bursts in 5-HT, whereas in dopamine the activity was shifted to a predominantly extensor-like pattern. 5. The relationship between flexor and extensor burst duration and cycle duration was more variable than described for locomotor activity in adult animals. 6. The relative timing of muscle activity was stable from P0 to P4. The most important difference between rats aged 0-1 days and rats aged 2-4 days was a delayed flexor-extensor transition in older animals. 7. The complex timing of hindlimb muscle activity was relatively unchanged after transecting all dorsal roots. 8. Finally, the relationship between flexor and extensor activity and ventral root discharges was determined. It was found that the L2 ventral root burst was in phase with simple flexors while the L5 burst coincide with the extensor phase. 9. We conclude, that 5-HT and dopamine can activate spinal central pattern generators (CPGs) that already at birth are able to produce distinct patterns of motor activity. Modulatory inputs thus seems to be able to reconfigure the CPGs to produce specific motor outputs.

scholarly journals Presynaptic Angiotensin II AT1 Receptors Enhance Inhibitory and Excitatory Synaptic Neurotransmission to Motoneurons and Other Ventral Horn Neurons in Neonatal Rat Spinal Cord

2005 ◽  
Vol 94 (2) ◽  
pp. 1405-1412 ◽  
Author(s):  
Murat Oz ◽  
Keun-Hang Yang ◽  
Michael J. O'Donovan ◽  
Leo P. Renaud
Keyword(s):  
Spinal Cord ◽  
Angiotensin Ii ◽  
Ventral Horn ◽  
Synaptic Activity ◽  
Neonatal Rat ◽  
Ang Ii ◽  
Synaptic Neurotransmission ◽  
Excitatory Neurotransmission ◽  
Ventral Spinal Cord

In neonatal spinal cord, we previously reported that exogenous angiotensin II (ANG II) acts at postsynaptic AT1 receptors to depolarize neonatal rat spinal ventral horn neurons in vitro. This study evaluated an associated increase in synaptic activity. Patch clamp recordings revealed that 38/81 thoracolumbar (T7–L5) motoneurons responded to bath applied ANG II (0.3–1 μM; 30 s) with a prolonged (5–10 min) and reversible increase in spontaneous postsynaptic activity, selectively blockable with Losartan ( n = 5) but not PD123319 ( n = 5). ANG-II-induced events included both spontaneous inhibitory (IPSCs; n = 6) and excitatory postsynaptic currents (EPSCs; n = 5). While most ANG induced events were tetrodotoxin-sensitive, ANG induced a significant tetrodotoxin-resistant increase in frequency but not amplitude of miniature IPSCs ( n = 7/13 cells) and EPSCs ( n = 2/7 cells). In 35/77 unidentified neurons, ANG II also induced a tetrodotoxin-sensitive and prolonged increase in their spontaneous synaptic activity that featured both IPSCs ( n = 5) and EPSCs ( n = 4) when tested in the presence of selective amino acid receptor antagonists. When tested in the presence of tetrodotoxin, ANG II was noted to induce a significant increase in the frequency but not the amplitude of mIPSCs ( n = 9) and mEPSCs ( n = 8). ANG also increased spontaneous motor activity from isolated mouse lumbar ventral rootlets. Collectively, these observations support the existence of a wide pre- and postsynaptic distribution of ANG II AT1 receptors in neonatal ventral spinal cord that are capable of influencing both inhibitory and excitatory neurotransmission.

Analysis of EPSCs and IPSCs Carrying Rhythmic, Locomotor-Related Information in the Isolated Spinal Cord of the Neonatal Rat

1997 ◽  
Vol 78 (4) ◽  
pp. 1851-1859 ◽  
Author(s):  
Morten Raastad ◽  
Bruce R. Johnson ◽  
Ole Kiehn
Keyword(s):  
Spinal Cord ◽  
Time Delays ◽  
Information Transfer ◽  
Large Range ◽  
Rhythmic Activity ◽  
Neonatal Rat ◽  
Mathematical Function ◽  
Reciprocal Regulation ◽  
Related Information ◽  
Current Trace

Raastad, Morten, Bruce R. Johnson, and Ole Kiehn. Analysis of EPSCs and IPSCs carrying rhythmic, locomotor-related information in the isolated spinal cord of the neonatal rat. J. Neurophysiol. 78: 1851–1859, 1997. To understand better the synaptic language used by neurons in active networks, we have analyzed postsynaptic currents (PSCs) received by interneurons in the isolated spinal cord from neonatal rats during 5-hydroxytryptamine- and N-methyl-d-aspartate–induced fictive locomotion. Using a computer algorithm, we identified PSCs in rhythmically active interneurons in laminae VII and X. To test whether the PSCs actually participated in the transmission of the cyclic, locomotor-related signal, we constructed an analytic current trace based on only the identified events. Each identified PSC was fitted by a mathematical function, and the shape of this function was added to a baseline with time delays given by the time positions of the identified PSCs. By averaging the resulting analytic current trace over several cycles, we showed that the identified PSCs built a cyclic signal locked to the rhythmic activity recorded from the ventral roots. Furthermore, subtraction of the analytic from the original current trace reduced the amplitude of the cyclic signal received by these cells. Thus the identified PSCs contributed to the cyclic information, allowing us to analyze how they built the compound cyclic signal. Most often there was an inverse relationship between the contribution from excitatory and inhibitory PSCs during the cyclic modulation, indicating that there was a reciprocal regulation of the presynaptic inhibitory and excitatory cells. Comparing the most inhibitory and most excitatory halves of the locomotor related cycle, there was a considerably larger modulation of the frequency of PSCs than of their amplitude. The small and sometimes insignificant modulation of PSC amplitude suggests that facilitation and depression had little importance for the information transfer. The modest amplitude modification also suggests that the large range of available PSC amplitudes seen in these neurons was not used very efficiently to code the cyclic information.

Opioid receptor modulation of GABAergic and serotonergic spinally projecting neurons of the rostral ventromedial medulla in mice

2011 ◽  
Vol 106 (2) ◽  
pp. 731-740 ◽  
Author(s):  
Nigel P. Pedersen ◽  
Christopher W. Vaughan ◽  
MacDonald J. Christie
Keyword(s):  
Spinal Cord ◽  
Opioid Receptor ◽  
Tryptophan Hydroxylase ◽  
Rostral Ventromedial Medulla ◽  
Inhibitory Influence ◽  
Receptor Modulation ◽  
Outward Currents ◽  
Neuronal Mechanisms ◽  
Ventromedial Medulla

The rostral ventromedial medulla (RVM) is an important site of opioid actions and forms part of an analgesic pathway that projects to the spinal cord. The neuronal mechanisms by which opioids act within this brain region remain unclear, particularly in relation to the neurotransmitters GABA and serotonin. In the present study, we examined serotonergic and GABAergic immunoreactivity, identified using immunohistochemistry for tryptophan hydroxylase (TPH) and glutamate decarboxylase (GAD), in combination with in vitro whole cell patch clamping to investigate the role of opioids on the mouse RVM with identified projections to the spinal cord. Tyr-d-Ala-Gly- N-Me-Phe-Gly-ol enkephalin (DAMGO) produced μ-opioid receptor-mediated outward currents in virtually all TPH-immunoreactive projecting neurons and GAD-immunoreactive nonprojecting neurons (87% and 86%). The other groups of RVM neurons displayed mixed responsiveness to DAMGO (40–68%). Deltorphin II and U-69593 produced δ- and κ-opioid receptor-mediated outward currents in smaller subpopulations of RVM neurons, with many of the δ-opioid responders forming a subpopulation of μ-opioid-sensitive GABAergic nonprojecting neurons. These findings are consistent with prior electrophysiological and anatomic studies in the rat RVM and indicate that both serotonergic and GABAergic RVM neurons mediate the actions of μ-opioids. Specifically, μ-opioids have a direct postsynaptic inhibitory influence over both GABAergic and serotonergic neurons, including those that project to the dorsal spinal cord.

scholarly journals Flexibility of Motor Pattern Generation Across Stimulation Conditions by the Neonatal Rat Spinal Cord

2010 ◽  
Vol 103 (3) ◽  
pp. 1580-1590 ◽  
Author(s):  
David A. Klein ◽  
Angelica Patino ◽  
Matthew C. Tresch
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Muscle Activation ◽  
Motor Pattern ◽  
Pattern Generation ◽  
Neonatal Rat ◽  
Rat Spinal Cord ◽  
Afferent Pathways ◽  
Motor Pattern Generation ◽  
Stimulation Of

Previous studies have demonstrated that “locomotor-like” rhythmic patterns can be evoked in the isolated neonatal rat spinal cord by several means, including pharmacological neuromodulation and electrical stimulation of various pathways. Recent studies have used stimulation of afferent pathways to evoke rhythmic patterns, relying on synaptic activation of interneuronal systems rather than global imposition of neuromodulatory state by pharmacological agents. We use the in vitro neonatal rat spinal cord with attached hindlimb to examine the muscle activation patterns evoked by stimulation of these different pathways and evaluate whether stimulation of these pathways all evoke the same patterns. We find that the patterns evoked by bath application of serotonin (5-HT) and N-methyl-d-aspartic acid (NMDA) consisted of alternation between hip flexors and extensors and similar alternation was observed in the patterns evoked by electrical stimulation of the cauda equina (CE) or contralateral fifth lumbar (L5) dorsal nerve root. In contrast, the knee extensor/hip flexor rectus femoris (RF) and knee flexor/hip extensor semitendinosus (ST) were activated differentially across stimulation conditions. In 5-HT/NMDA patterns, RF was active in late flexion and ST in late extension. In CE patterns, these two muscles switched places with RF typically active in late extension and ST active in flexion. In L5 patterns, ST was activated in extension and RF was silent or weakly active during flexion. There were also systematic differences in the consistency of rhythms evoked by each stimulation method: patterns evoked by electrical stimulation of CE or L5 were less consistently modulated with the rhythm when compared with 5-HT/NMDA-evoked patterns. All differences were preserved following deafferentation, demonstrating that they reflect intrinsic properties of spinal systems. These results highlight the intrinsic flexibility of motor pattern generation by spinal motor circuitry which is present from birth and provides important information to many studies examining spinal pattern generating networks.

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