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S W Thompson

Publications and source records attributed to S W Thompson.

At least 37 records · Page 2Linked to original sources
PubMed1996

Leukemia inhibitory factor induces mechanical allodynia but not thermal hyperalgesia in the juvenile rat.

Systemic administration or local injection to the rat hindpaw of leukemia inhibitory factor induced a prolonged, dose dependent, mechanical hypersensitivity of the hindpaw flexion withdrawal reflex. Mechanical stimuli which were innocuous prior to leukemia inhibitory factor administration, evoked a rapid hindpaw withdrawal reflex indicative of mechanical allodynia. Pre-administration of anti-leukemia inhibitory factor antibodies prevented this behavioural hypersensitivity. Hindpaw sensitivity to a noxious thermal stimulus was unaffected by leukemia inhibitory factor administration. Anti-leukemia inhibitory factor had no effect upon hindpaw withdrawal thresholds when injected alone nor influenced the mechanical hypersensitivity produced by a subcutaneous injection of nerve growth factor. Injection of the closely related cytokine ciliary neurotrophic factor did not affect mechanical or thermal reflex withdrawal thresholds. Elevation of the neuroactive cytokine leukemia inhibitory factor following peripheral nerve injury may be a contributory factor to the pathogenesis of neuropathic pain.

Age Factors↗
PubMed1996

Metabotropic glutamate receptor activation contributes to nociceptive reflex activity in the rat spinal cord in vitro.

The contribution of metabotropic glutamate receptor activation to the spinal segmental reflex response evoked at high-intensity electrical stimulation suggesting a role in nociception, has been examined in an in vitro preparation of neonatal rat spinal cord. Segmental reflex responses were recorded as a ventral root depolarization evoked following drug perfusion to the spinal cord or by electrical activation of high-threshold nociceptive afferent fibres. Superfusion of the selective metabotropic glutamate receptor agonist, (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD], to the spinal cord produced a dose-dependent, reversible ventral root depolarization (EC50 = 58 +/- 7 microM; n = 4), which was antagonized by the selective metabotropic glutamate receptor antagonist, (+)-alpha-methyl-4-carboxyphenylglycine (MCPG; IC50 = 243 +/- 61 microM; n = 4). MCPG, over the same concentration range (10 microM-5.0 mM) did not affect N-methyl-D-aspartate-induced ventral root depolarizations. In contrast, the specific N-methyl-D-aspartate receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) reduced N-methyl-D-aspartate-evoked ventral root depolarization but did not affect the depolarization evoked by (1S,3R)-ACPD, thus indicating the specificity of the antagonists for these aggregate responses. MCPG significantly reduced the prolonged phase of the single shock C-fibre-evoked ventral root depolarization (IC50 = 2.9 +/- 0.2 mM; n = 3-5). Low frequency high intensity stimulation of the dorsal root evoked a wind-up response, the amplitude of which was attenuated by both D-AP5 and MCPG in a dose-dependent manner. The ventral root depolarization evoked by capsaicin application (1.0 microM, 30 s) was blocked by both MCPG (IC50 = 809 +/- 35 microM; n = 4) and D-AP5 (IC50 = 143 +/- 43 microM; n = 4). These data suggest that both D-AP5 and MCPG reduced C-fibre-induced ventral root responses. In addition to N-methyl-D-aspartate receptor, metabotropic glutamate receptor activation appears to be involved in the generation of the segmental spinal reflex evoked by high-intensity stimulation in the neonatal rat spinal cord in vitro.

Animals↗
PubMed1995

No evidence for contribution of nitric oxide to spinal reflex activity in the rat spinal cord in vitro.

The effects of nitric oxide (NO) synthase inhibition, NO generation and an N-methyl-D-aspartic acid (NMDA) receptor antagonist upon spinal reflex responses evoked by electrical activation of high threshold afferent fibres and brief application of NMDA have been compared in an in vitro preparation of the neonatal rat spinal cord. Reflex responses of spinal cords prepared from naive animals and those exhibiting a behavioural hyperreflexia following UV irradiation of the left hindpaw have been compared. C-fibre evoked and NMDA induced ventral root potential responses were significantly reduced by the selective NMDA receptor antagonist D-AP5 (40 microM) but completely unaffected by application of 7-nitroindazole (30 microM), NG-nitro-L-arginine methyl ester (L-NAME; 100 microM) or sodium nitroprusside (50 microM) either in hyperalgesic or naive animals. In vivo behavioural experiments performed upon age-matched rat pups showed that reflex sensitivity was significantly reduced following administration of L-NAME (30 mg kg-1). The present study has failed to provide evidence that NO is involved in nociceptive spinal reflex activity measured in vitro. In contrast, an NO synthase inhibitor was shown to influence nociceptive reflex responses observed in vivo. We suggest it is possible that NO participates in post-injury induced hyperreflexia at sites other than directly upon spinal neurones.

2-Amino-5-phosphonovalerate↗
PubMed1994

Modulation of spinal excitability: co-operation between neurokinin and excitatory amino acid neurotransmitters.

Activation of C fibres with strong 'potentially tissue damaging' chemical, mechanical or thermal stimuli produces painful sensations that are significantly enhanced during pathological conditions, such as neuropathy and inflammation. The pronounced painful symptoms of hyperalgesia and allodynia are induced, in part, by the development of spinal hyperexcitability. This involves plastic changes in synaptic transmission between primary afferents and dorsal horn neurones induced by sustained activity of peripheral nociceptors. L. Urban, S. W. N. Thompson and A. Dray describe some of the central mechanisms that account for central hyperexcitability occurring in hyperalgesia and allodynia based on evidence from experiments both in vivo and in vitro with neurokinin and N-methyl-D-aspartate receptor antagonists.

Animals↗
PubMed1994

Injury-induced plasticity of spinal reflex activity: NK1 neurokinin receptor activation and enhanced A- and C-fiber mediated responses in the rat spinal cord in vitro.

A- and C-fiber evoked ventral root potential (VRP) responses have been examined in isolated spinal cord preparations maintained in vitro that were taken from young rats in which behavioral hyperalgesia (thermal and mechanical) was induced following UV irradiation of one hindpaw. Evoked VRPs were compared with those in naive untreated animals. The duration of both the A- and C-fiber evoked VRP was significantly increased in UV-treated animals. The amplitude of the summated VRP evoked by repeated low-frequency (1.0-5.0 Hz) C-fiber stimulation, a measure of windup, was significantly greater in UV-treated animals. In UV-treated animals, repeated low-frequency (1.0-5.0 Hz) stimulation of A-fiber inputs to the spinal cord also evoked a significant summated VRP, which was not observed in spinal cords from untreated animals. In naive animals the prolonged VRP evoked following single shock C-fiber stimulation was significantly antagonized by the NMDA receptor antagonist D-AP5 and the NK2 receptor antagonist MEN, 10376 but not by the NK1 receptor antagonists CP-96,345 or RP,67580. Summated VRPs evoked by repeated C-fiber stimulation in naive animals were significantly antagonized only by D-AP5. In hyperalgesic animals the prolonged VRP evoked by C-fiber stimulation was significantly reduced by NK1, NK2, and NMDA antagonists. The summated VRP was also significantly reduced by these antagonists. In both untreated and UV-irradiated animals the single shock evoked A-fiber ventral root response was significantly antagonized only by D-AP5. However, the summated VRP evoked by repeated A-fiber stimulation in UV-treated animals was also significantly reduced by NMDA, NK1, and NK2 receptor antagonists. The present study has demonstrated enhanced A- and C-fiber evoked responses in the rat spinal cord in vitro following induction of a peripheral injury by UV irradiation and which was associated with behavioral hyperalgesia to thermal and mechanical stimuli. Under this condition, repetitive stimulation of A-fiber primary afferents was capable of producing an enhancement of spinal excitability similar to that evoked by C-fibers in normal animals. Furthermore, we have observed the expression of an NK1 receptor component to the C-fiber evoked response following the establishment of the peripheral injury. The enhanced ventral root responses and changes in receptor sensitivity may contribute to the phenomenon of central sensitization and may be directly related to the behavioral hyperalgesia observed. Moreover, these findings may be relevant to the mechanisms of enhanced central excitability that occur in clinical conditions of inflammatory hyperalgesia and neuropathic pain.

Animals↗
PubMed1993

Contribution of NK1 and NK2 receptor activation to high threshold afferent fibre evoked ventral root responses in the rat spinal cord in vitro.

The contribution of neurokinin and NMDA receptor activation to the generation of the prolonged high threshold evoked ventral root potential (VRP) and its temporal summation has been assessed in the neonatal rat hemisected spinal cord maintained in vitro. High intensity single shock stimulation of the dorsal roots evoked a prolonged VRP (9.81 +/- 0.9 s, n = 11). A low frequency (1-10 Hz) repetitive stimulation (20 s duration) of high threshold afferent fibres evoked a summated VRP. This summated VRP reflected the temporal summation of EPSP's in spinal cord neurones which underlies the phenomenon of 'Windup'. The integrated area and duration of the high threshold evoked VRP were significantly reduced following superfusion of the spinal cord with the NK2 receptor antagonist MEN,10376 (100 nM). In the presence of D-AP5 (20 microM) the area of the C-fibre evoked VRP was also significantly reduced. The VRP duration was unaffected. Superfusion with either CP-96,345 (500 nM) or RP,67580 (100 nM), both non-peptide NK1 antagonist, did not have any significant effect upon the area or duration of the prolonged VRP following high threshold stimulation. The simultaneous application of D-AP5 (20 microM) with either MEN,10376 (100 nM) or CP-96,345 (500 nM) together produced a reduction in the area of the evoked VRP which was comparable to the value obtained by addition of their individual effects. The amplitude of the summated VRP was significantly reduced following application of D-AP5 (20 microM). No significant effect upon the amplitude was observed following separate application of either MEN,10376 (100 nM), CP-96,345 (500 nM) or RP,67580 (100 nM).(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1993

Rate of rise of the cumulative depolarization evoked by repetitive stimulation of small-caliber afferents is a predictor of action potential windup in rat spinal neurons in vitro.

1. The summation of depolarizing postsynaptic potentials (PSPs) evoked by stimulation of primary afferent fibers in lumbar dorsal roots was studied in dorsal and ventral horn neurons in the rat hemisected spinal cord in vitro with current-clamp intracellular recording techniques. PSPs evoked by activation of A delta and/or C fibers could summate after repetitive stimulation at low frequencies: this resulted in a progressive, long-lasting change in the neuronal membrane potential (Vm) (cumulative depolarization). Cumulative depolarization was not observed after stimulation at A beta-fiber intensity or at frequencies < 0.2 Hz. 2. Effective PSP summation resulting in a significant cumulative depolarization (> 5 mV) was observed only if the PSPs evoked were longer than 4 s. On the other hand, there was no correlation between the amplitude of cumulative depolarization achieved in a neuron and the absolute duration of the PSP or the neuronal resting membrane properties (Vm and input resistance). 3. With relation to the changes in Vm during the stimulation train, three patterns of response to repetitive stimuli could be detected in both dorsal horn (DH) and ventral horn (VH) neurons: 1) little or no depolarization throughout the train; 2) an initial depolarization, which either remained stationary or decayed to the resting Vm after the first 3-4 s of stimulation; or 3) a progressive cumulative depolarization increasing throughout the train. 4. Depolarizing the cell by DC current injection resulted in a steeper rise in Vm in response to repetitive stimuli in one half of VH neurons and in one out of nine DH neurons tested. 5. Action potential windup, an increase in the number of action potentials elicited by each stimulus as the train progresses, was observed both in DH and in VH cells. C-fiber strength stimulation was the most effective in eliciting windup. Windup was associated with Vm responses to repetitive stimulation belonging to the progressive cumulative depolarization pattern. Indeed, cumulative depolarizations that resulted in windup had significantly steeper slopes for the Vm trajectory than those that did not. In those neurons in which DC depolarization by intracellular current injection increased the slope of the Vm trajectory, DC depolarization could also bring about action potential windup. 6. These results indicate that, although the generation of long-lasting "slow" PSPs by high-threshold primary afferents is necessary for the summation of synaptic activity in the spinal cord at low frequencies, the rate and pattern of the summation does not depend on the absolute duration of the PSPs.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1993

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.

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)

Action Potentials↗
PubMed1993

Trifocal independent periodic lateralized epileptiform discharges.

The EEG of a 2 1/2-year-old female with a severe cerebral insult showed trifocal periodic lateralized epileptiform discharges (TRIPLEDs). We believe this is the first such record reported. As with BIPLEDs, the physical findings associated with this EEG appear to represent a diffuse cerebral insult. The most frequent causes of BIPLEDs are diffuse anoxic encephalopathy and CNS infection. In this patient, the TRIPLEDs are apparently due to a severe anoxic insult suffered in utero. As is true with BIPLEDs, the presence of TRIPLEDs represents a poor prognosis.

Asphyxia Neonatorum↗
PubMed1992

Long duration ventral root potentials in the neonatal rat spinal cord in vitro; the effects of ionotropic and metabotropic excitatory amino acid receptor antagonists.

Long duration, primary afferent evoked ventral root potentials (VRP's) have been recorded in vitro from hemisected spinal cords prepared from 8-12-day-old rat pups. Single shock stimulation of a dorsal root at stimulus strengths sufficient to recruit C/group IV afferent fibres evoked a long duration (11.9 +/- 1.2 s) ipsilateral VRP in all preparations. This long duration VRP consisted of two components, (i) a slow wave, time to peak 137.0 +/- 5.1 ms, the amplitude of which was reduced to 8.7% of mean control value in the presence of the N-methyl-D-aspartate (NMDA) antagonist D-AP5 (40 microM), (ii) a prolonged wave with a time to peak of 2.0 +/- 0.2 s which was partially resistant to D-AP5 (40 microM). Both the slow and the prolonged waves were unaffected following superfusion with the metabotropic excitatory amino acid (EAA) receptor antagonist L-AP3 (100-200 microM). Low frequency (1-10 Hz) repetitive stimulation (20 s duration) of high threshold dorsal root afferents evoked a temporal summation of synaptic activity which generated a progressively depolarizing VRP. This cumulative VRP was graded with frequency of stimulation (0.89 +/- 0.13 to 1.25 +/- 0.19 mV). The cumulative VRP was followed by a post-stimulus depolarization which outlasted the period of repetitive stimulation by tens of seconds (47.6 +/- 8.4 to 91.2 +/- 19.9 s). In the presence of AP5 the amplitude of the cumulative VRP was depressed to 54.5 +/- 11.5% of control values when low frequency (1.0 Hz) stimulation was used. The proportion of the cumulative VRP resistant to D-AP5 increased as the frequency of stimulation was increased to 10 Hz. The decay time of the post-stimulus depolarization was unaffected by AP5. Neither the amplitude nor the post-stimulus depolarization of the cumulative VRP was affected by 200 microM L-AP3. It is suggested that both an AP5 sensitive and AP5 insensitive potential contribute to the long duration VRP evoked in the neonatal rat spinal cord following single shock high threshold afferent stimulation. Moreover, the AP5 insensitive prolonged depolarization is manifest following sustained low frequency stimuli and higher frequency inputs.

2-Amino-5-phosphonovalerate↗
PubMed1990

Characterization of the cutaneous input to the ventral horn in vitro using the isolated spinal cord-hind limb preparation.

Intracellular recordings were made from 21 ventral horn neurones including 7 flexor motoneurones in a 10-12-day-old rat isolated spinal cord-hind limb preparation. The cutaneous input to these neurones was assessed using natural mechanical stimulation within the cutaneous mechanoreceptive field or electrical stimulation of the sural nerve. The receptive fields of 10 ventral horn neurones including 3 flexor motoneurones were characterized: 60% of cells responded to both low (touch) and high (pinch) threshold mechanical stimulation of the skin while the remaining 40% responded only to noxious mechanical stimuli. The postsynaptic response consisted of either purely subthreshold polysynaptic EPSPS (n = 8) or graded sub- and suprathreshold EPSPS (n = 2). The duration of the EPSP was typically prolonged by as much as a factor of ten compared to duration of the mechanical stimulation. In another 11 neurones (4 flexor motoneurones) the pattern of the postsynaptic response was related to the intensity of sural nerve stimulation. A low intensity single shock produced a short latency (30 ms), short duration EPSP (less than 500 ms) while higher intensities elicited a longer duration (greater than 1 s), more complex EPSP. In 36% of cells tested the EPSP remained subthreshold for cell firing even at the highest stimulus intensity.

Animals↗
PubMed1990

Activity-Dependent Changes in Rat Ventral Horn Neurons in vitro; Summation of Prolonged Afferent Evoked Postsynaptic Depolarizations Produce a d-2-Amino-5-Phosphonovaleric Acid Sensitive Windup.

The synaptic responses of lumbar ventral horn neurons including identified flexor motoneurons, to graded stimulation of peripheral nerves have been recorded in vitro in the young rat spinal cord-hindlimb preparation. Single shock stimulation of low threshold myelinated afferents evoked short latency (< 20 ms) short duration (< 1.0 s, 391 +/- 42 ms n=43 SEM) compositive mono- and polysynaptic potentials. Recruitment of both thinly myelinated (A delta) and unmyelinated (C) afferent fibres elicited a prolonged postsynaptic depolarization (> 1 s) in all cells. In the majority of cells (67.4%), this depolarization exceeded 4.0 s in duration (8.01 +/- 0.4 s, n=26, maximum 14 s). In the remainder, shorter responses were evoked (< 3.0 s, mean=1.74 +/- 0.4 s, n=18). In those cells where the postsynaptic response to a single A delta or C fibre strength stimulus exceeded 4 s, low frequency (0.5 - 1.0 Hz) repetitive stimulation resulted in a temporal summation of the postsynaptic depolarizations, which generated a cumulatively increasing depolarization. This incrementing depolarization was sufficient in 33% of the cells to produce a progressive increase in spike discharge (windup). On cessation of the train of stimuli the depolarization decayed slowly (65 +/- 27 s). The N-methyl d-aspartic acid (NMDA) receptor antagonist d-2-amino-5-phosphonovaleric acid (d-APV) reduced the duration and amplitude of the prolonged postsynaptic depolarizations elicited by a single shock stimulation of small diameter afferents by 57% and 50% respectively. A smaller effect was produced on the low threshold afferent evoked early excitatory postsynaptic potentials (EPSP) (3% decrease in amplitude and 24% decrease in duration). In the presence of d-APV the cumulatively incrementing depolarization produced by repetitive stimulation was substantially reduced and windup failed to occur. Activity-dependent amplifications of primary afferent evoked responses in spinal neurons therefore involves a temporal summation of d-APV sensitive prolonged postsynaptic depolarizations.

Journal Article↗
PubMed1989

A subchronic toxicity study of octyl acetate in rats.

The subchronic toxicity of octyl acetate was assessed following its administration to rats via oral gavage, 5 days per week for 13 weeks. Treated rats received undiluted octyl acetate at doses of 0.1, 0.5, or 1.0 g/kg. Control rats received distilled water at a dose of 1.0 g/kg. An interim termination was made after 45 days of dosing at which time five animals per sex per group were terminated and necropsied. Blood samples were collected and liver tissues were prepared for histological examination. After 13 weeks of dosing all animals were terminated and necropsied. Blood samples were obtained and selected organs were weighed and prepared for subsequent histological examination. Several treatment-related effects were observed in the high-dose group (1.0 g/kg) animals. These effects included slight reductions in body weight and food consumption, increased liver and kidney weights, and evidence of hydrocarbon nephropathy in high-dose males only. The significance of these observations is discussed in the report. With the exception of increased liver weights in the mid-dose group, no other significant treatment-related effects were observed in the mid- or low-dose groups of animals. It is believed that the increases in liver weight which were observed are a compensatory response to an increased metabolic load, and not a reflection of true hepatotoxicity. The results of this study indicated that octyl acetate possessed an overall low degree of systemic toxicity when administered orally to rats for 13 weeks.

Acetates↗
PubMed1989

Characterization of deep dorsal horn neurones in the rat spinal cord in vitro: synaptic and excitatory amino acid induced excitations.

1. Two in vitro spinal cord preparations obtained from young rats (10-16 days), the transverse slice and the hemisected cord, have been utilized to examine the properties of deep dorsal horn neurones. 2. Several features have emerged: neurones respond to direct current injection with repetitive firing which is characteristically tonic in nature with little adaptation. Over the current intensities tested, no secondary firing range was apparent. 3. Graded afferent fibre stimulation produces a variety of sub- and suprathreshold postsynaptic excitatory potentials. The latencies of these potentials range from tens of milliseconds to hundreds of milliseconds, with the former predominating. 4. The majority of neurones are strongly excited by all three agonists: glutamate, quisqualate and N-methyl-D-aspartate but in addition a subpopulation of neurones with low sensitivity to glutamate and N-methyl-D-aspartate exists. 5. The implications of such properties for sensory processing within the dorsal horn are discussed.

Animals↗
PubMed1988

An intracellular analysis of amino acid induced excitations of deep dorsal horn neurones in the rat spinal cord slice.

The rat spinal cord slice preparation has been used to investigate the sensitivity of deep dorsal horn neurones to the excitatory amino acids N-methyl-D-aspartate (NMDA), quisqualate and L-glutamate. Intracellular recordings were made from 44 neurones in laminae III-VI of 14- to 16-day rats. Superfusion of quisqualate (30 microM) excited all neurones, NMDA (50 microM) excited 72% and L-glutamate (0.5-1 mM) 63% of the neurones. Depolarizations were retained after tetrodotoxin but with a reduced amplitude. The NMDA antagonist D-aminophosphonovalerate (D-APV, 10 microM) reduced NMDA and L-glutamate depolarizations by 66% and by 40%, respectively, while the quisqualate responses were enhanced by 27%. Dorsal root stimulation elicited two main patterns of activity; short-latency single/double spikes followed by subthreshold excitatory postsynaptic potentials (EPSPs) or a burst of spikes rising from a long duration composite EPSP. D-APV reduced the long-latency components of the first type and reduced the amplitude and duration of the composite EPSP of the second. These results support a specialized role for NMDA receptors in synaptic transmission in the dorsal horn.

2-Amino-5-phosphonovalerate↗
PubMed1988

The responses recorded in vitro of deep dorsal horn neurons to direct and orthodromic stimulation in the young rat spinal cord.

The electrophysiological properties of 87 neurons in the deep dorsal horn (laminae III-VI) of the rat spinal cord have been investigated in vitro. Two preparations have been used; the transverse spinal cord slice preparation from the third or fourth lumbar segments of 14-16-day-old rats (71 cells) and a hemisected lumbar spinal cord preparation from 10-12-day-old rats (16 cells). The input impedances (range 11-128 M omega), membrane potentials (-67 +/- 8 mV S.D.), action potential amplitude (77 +/- 11.8 mV) duration (1.4 +/- 0.5 ms) and afterpotentials, were effectively identical in the neurons recorded from the two preparations. Neurons in both preparations when activated with long-duration (1-2 s) outward current pulses showed a single steady-state firing range with little adaptation of firing frequency or action potential amplitude. This pattern of responses was unaffected by changing the membrane potential. Orthodromic synaptic activity could be elicited in the neurons by stimulating either the small dorsal root remnants in the slice or the dorsal roots in the hemisected spinal cord. The responses evoked by single stimuli of increasing intensity varied in different neurons in both preparations. The commonest response (32/62) consisted of a short-latency, short-duration composite excitatory postsynaptic potential which generated one or two spikes with no further spiking activity at longer latency when the stimulus intensity was increased beyond threshold. In 20 neurons, graded stimulation produced a graded response with recruitment, at high intensities, of a discharge of action potentials lasting several hundred milliseconds. A small number of cells (4) responded to the single stimulus with a train of action potentials lasting several seconds. Stimulating adjacent dorsal roots in the hemisected cord preparation could evoke quite different responses from the neurons. The heterogeneity of the types of orthodromic responses obtained in both preparations, in spite of the almost uniform intrinsic membrane properties, is likely to reflect differences in the strength, location and type of afferent and interneuronal input to different dorsal horn cells.

Action Potentials↗
PubMed1988

Hyperpolarizing responses to stretch in sensory neurones innervating leech body wall muscle.

1. The membrane properties, morphology and physiological responses of peripherally located sensory neurones that innervate body wall muscle of the leech Hirudo medicinalis have been investigated using intracellular recording and dye injection techniques. 2. The peripheral neurones and their dendrites were visualized directly in whole mounts of the body wall by intracellular injection of horseradish peroxidase or Lucifer Yellow. They lie along the course of segmental nerves between the layers of longitudinal and oblique body wall muscle and within the sheath of the nerve. They have a distinctive morphology with two expanded, fan-shaped dendrites arranged in series separated by the cell body and a 300 micron long cylindrical process. Both dendrites are associated with longitudinal muscle of the ventral body wall but with separate bands of muscle fibres. The axons project into the ventral nerve cord and arborize within the ipsilateral half of the segmental ganglion. No processes extend across the mid-line of the ganglion or enter the connectives to neighbouring ganglia. 3. 'Resting' membrane potentials recorded from the peripheral cell body or from the axon as it entered the segmental ganglion ranged from -30 to -70 mV. The transmembrane potential recorded depended on the amount by which the body wall was stretched: the most hyperpolarized values were recorded from the most stretched preparations. Although the peripheral cell body can generate overshooting action potentials these are not actively propagated to the CNS. Rather, imposed voltage changes spread decrementally along the axon. Input resistances measured in the cell body ranged from 14 to 26 M omega. The space constant, estimated from the spread of hyperpolarizing current injected into the cell body, was 2.4 mm. 4. The response of the neurones to change in length of the longitudinal muscle recorded from the axon near its terminal arborization within the ventral nerve cord is a graded DC signal: the neurones thus relay information to CNS synapses in analogue form. Spiking activity recorded extracellularly in the anterior segmental nerve root in response to stretch of the body wall is due to activation of touch mechanosensory cells that innervate the skin. 5. Unlike stretch receptors innervating skeletal muscle in vertebrates or arthropods, the leech neurones respond to stretch of the body wall muscle with maintained hyperpolarizing potentials and to release of stretch with depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗