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Biomedical subjects

J Hounsgaard

Publications and source records attributed to J Hounsgaard.

At least 19 recordsLinked to original sources
PubMed2001

Electrotonic structure of motoneurons in the spinal cord of the turtle: inferences for the mechanisms of bistability.

Understanding how voltage-regulated channels and synaptic membrane conductances contribute to response properties of neurons requires reliable knowledge of the electrotonic structure of dendritic trees. A novel method based on weak DC field stimulation and the classical method based on current injection were used to obtain two independent estimates of the electrotonic structure of motoneurons in an in vitro preparation of the turtle spinal cord. DC field stimulation was also used to ensure that the passive membrane properties near the resting membrane potential were homogeneous. In two cells, the difference in electrotonic lengths estimated with the two methods in the same cell was 6 and 9%. The majority of dendritic branches terminated at a distance of 1 electrotonic unit from the recording site. The longest branches reached 2 lambda. In the third cell, the difference was 36%, demonstrating the need to use both methods, field stimulation and current injection, for reliable measurements of the electrotonical structure. Models of the reconstructed cells endowed with voltage-dependent conductances were used to explore generation mechanisms for the experimentally observed hysteresis in input current-voltage relation of bistable motoneurons. The results of modeling suggest that only some dendrites need to possess L-type calcium current to explain the hysteresis observed experimentally and that dendritic branches with different electrotonical lengths can be bistable. Independent bistable behavior in individual dendritic branches can make motoneurons complex processing units.

Animals↗
PubMed2000

Development and regulation of response properties in spinal cord motoneurons.

The intrinsic response properties of spinal motoneurons determine how converging premotor neuronal input is translated into the final motor command transmitted to muscles. From the patchy data available it seems that these properties and their underlying currents are highly conserved in terrestrial vertebrates in terms of both phylogeny and ontogeny. Spinal motoneurons in adults are remarkably similar in many respects ranging from the resting membrane potential to pacemaker properties. Apart from the axolotls, spinal motoneurons from all species investigated have latent intrinsic response properties mediated by L-type Ca2+ channels. This mature phenotype is reached gradually during development through phases in which A-type potassium channels and T-type calcium channels are transiently expressed. The intrinsic response properties of mature spinal motoneurons are subject to short-term adjustments via metabotropic synaptic regulation of the properties of voltage-sensitive ion channels. Recent findings also suggest that regulation of channel expression may contribute to long-term changes in intrinsic response properties of motoneurons.

Action Potentials↗
PubMed2000

Dorsal root potential produced by a TTX-insensitive micro-circuitry in the turtle spinal cord.

1, The mechanisms underlying the dorsal root potential (DRP) were studied in transverse slices of turtle spinal cord. DRPs were evoked by stimulating one filament in a dorsal root and were recorded from another such filament. 2. The DRP evoked at supramaximal stimulus intensity was reduced but not eliminated after blockade of GABAA receptors. The remaining component was eliminated by blocking NMDA and AMPA receptors. 3. The DRP was reduced but not eliminated after blockade of AMPA receptors. The early component of the remaining DRP was dependent on GABAA receptors and the residual component on NMDA receptors. 4. The DRP was reduced but not eliminated by TTX. GABAA, NMDA and AMPA receptors contributed to the generation of the TTX-insensitive DRP. The early component of the DRP in the presence of TTX depended on GABAA receptor activation, and the late component mainly on the activation of NMDA receptors. 5. Our results show that part of the DRP is generated by a TTX-resistant, probably non-spiking micro-circuit with separate components mediated by GABA and glutamate.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2000

Facilitation of plateau potentials in turtle motoneurones by a pathway dependent on calcium and calmodulin.

1. The involvement of intracellular calcium and calmodulin in the modulation of plateau potentials in motoneurones was investigated using intracellular recordings from a spinal cord slice preparation. 2. Chelation of intracellular calcium with BAPTA-AM or inactivation of calmodulin with W-7 or trifluoperazine reduced the amplitude of depolarization-induced plateau potentials. Inactivation of calmodulin also inhibited facilitation of plateau potentials by activation of group I metabotropic glutamate receptors or muscarinic receptors. 3. In low-sodium medium and in the presence of tetraethylammonium and tetrodotoxin, calcium action potentials evoked by depolarization were followed by a short hyperpolarization ascribed to the calcium-activated non-selective cationic current (ICAN) and by a dihydropyridine-sensitive afterdepolarization. The amplitude of the afterdepolarization depended on the number of calcium spikes and was mediated by L-type calcium channels. 4. The dihydropyridine-sensitive afterdepolarization induced by calcium spikes was reduced by blockade of calmodulin. 5. It is proposed that plateau potentials in spinal motoneurones are facilitated by activation of a calcium-calmodulin-dependent pathway.

Animals↗
PubMed2000

Dedifferentiation of intrinsic response properties of motoneurons in organotypic cultures of the spinal cord of the adult turtle.

Explant cultures from the spinal cord of adult turtles were established and used to study the sensitivity of the intrinsic response properties of motoneurons to the changes in connectivity and milieu imposed by isolation in culture. Transverse sections 700 microm thick were explanted on cover slips and maintained in roller-tube cultures in medium containing serum and the growth factors brain-derived neurotrophin factor (BDNF), neurotrophin-3 (NT3), glial cell line-derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF). The gross morphology of acute sections was maintained after 4 weeks in culture. Cell bodies of motoneurons remained stainable in fixed cultures with an antibody against choline acetyltransferase (ChAT) throughout the culture period. During culture, motoneurons maintained stable resting membrane potentials and were contacted by functional synapses. The ability to generate action potentials was also preserved as was delayed inward rectification and generation of calcium spikes in the presence of tetra-ethyl ammonium (TEA). In response to depolarization, however, motoneurons presented strong outward rectification, and only 41% of the cells recorded from maintained the ability to fire repetitively. By the second week in culture, a fraction of motoneurons displayed fast and slow transient outward rectification and low-threshold calcium spikes, features not seen in turtle motoneurons in acute slices. On the other hand, properties mediated by L-type Ca2+ channels disappeared during the first few days in culture. Our observations show that the phenotypical intrinsic response properties of mature spinal motoneurons are modified in explant cultures. The properties acquired resemble the properties in juvenile motoneurons in several species of terrestrial vertebrates.

Action Potentials↗
PubMed2000

Detection of inhomogeneities in membrane ohmic resistance in geometrically complex systems.

DC field-evoked transients in arbitrarily shaped neurons and syncytia were analyzed theoretically. In systems with homogeneous passive membrane properties, the transients develop much faster than the membrane discharges. Conductance of the proximal membrane could be larger due to the injury imposed by sharp electrode impalement. In this case, the transients have an overshoot and an undershoot when the field is switched on and off. The overshoot and undershoot decay with the time constant of the response to current injection. If the conductance of the distal membrane is larger, the fast transients develop only partially and have slow tails which decay according to the time constant of the response to current injection. We recorded DC field-evoked potentials in motoneurons in turtle spinal cord slices by sharp electrodes and in the whole-cell mode. All three theoretically predicted types of responses were observed. The sharp electrodes were found not to impose a shunt in 60% of recorded cells. Detection of various membrane inhomogeneities in 1D-syncytium is discussed. We also suggest that it is possible to detect the inhomogeneities in intercellular resistance of the syncytium and intracellular resistance of a neuron when the membrane passive properties are homogeneous.

Animals↗
PubMed1999

Local facilitation of plateau potentials in dendrites of turtle motoneurones by synaptic activation of metabotropic receptors.

1. The spatial distribution of synaptic facilitation of plateau potentials in dendrites of motoneurones was investigated in transverse sections of the spinal cord of the turtle using differential polarization by applied electric fields. 2. The excitability of motoneurones in response to depolarizing current pulses was increased following brief activation of either the dorsolateral funiculus (DLF) or the medial funiculus (MF) even when synaptic potentials were eliminated by antagonists of ionotropic receptors. 3. The medial and lateral compartments of motoneurones were differentially polarized by the electric field generated by passing current between two electrodes on either side of the preparation. In one direction of the field lateral dendrites were depolarized while the cell body and medial dendrites were hyperpolarized (S- configuration). With current in the opposite direction the cell body and medial dendrites were depolarized while lateral dendrites were hyperpolarized (S + configuration). 4. Following brief activation of the DLF the excitability and the generation of plateau potentials were facilitated during differential depolarization of the lateral dendrites but not during differential depolarization of the cell body and medial dendrites. Following brief activation of the MF the excitability and generation of plateau potentials were facilitated during differential depolarization of the cell body and medial dendrites but not during differential depolarization of the lateral dendrites. 5. It is concluded that the synaptic facilitation of the dihydropyridine-sensitive response to depolarization is compartmentalized in turtle motoneurones.

Animals↗
PubMed1999

L-type calcium channels but not N-methyl-D-aspartate receptor channels mediate rhythmic activity induced by cholinergic agonist in motoneurons from turtle spinal cord slices.

Rhythmic activity induced by different combinations of N-methyl-D-aspartate (NMDA), serotonin (5-HT), muscarine and D-tubocurarine was monitored intracellularly in lumbar motoneurons in a slice preparation from adult turtles. Low concentration of NMDA (7.5-15 microM) combined with 5-HT (10-80 microM) induced rhythmic motoneuron discharge which was underlied by intrinsic voltage oscillations resistant to tetrodotoxin. This oscillatory activity was abolished by 2-amino-5-phosphonopentanoic acid (AP5), a competitive blocker of NMDA receptors and by nifedipine a selective blocker of L-type calcium channels. In contrast, rhythmicity induced by the cholinergic agents muscarine and d-tubocurarine was abolished by nifedipine but not by AP5 nor by high [Mg2+]o. These results show that different receptor agonists induce intrinsic oscillations in mature motoneurons by independent routes. Each oscillatory mechanism depends on L-type calcium channels but only NMDA/5-HT-induced oscillations depend on voltage-sensitive NMDA-activated ionophores.

Animals↗
PubMed1999

Dynamics of intrinsic electrophysiological properties in spinal cord neurones.

The spinal cord is engaged in a wide variety of functions including generation of motor acts, coding of sensory information and autonomic control. The intrinsic electrophysiological properties of spinal neurones represent a fundamental building block of the spinal circuits executing these tasks. The intrinsic response properties of spinal neurones--determined by the particular set and distribution of voltage sensitive channels and their dynamic non-linear interactions--show a high degree of functional specialisation as reflected by the differences of intrinsic response patterns in different cell types. Specialised, cell specific electrophysiological phenotypes gradually differentiate during development and are continuously adjusted in the adult animal by metabotropic synaptic interactions and activity-dependent plasticity to meet a broad range of functional demands.

Adult↗
PubMed1999

Non-volatile general anaesthetics reduce spinal activity by suppressing plateau potentials.

Non-volatile general anaesthetics are thought to reduce brain activity by potentiating inhibitory GABA(A) receptor channels but also cause adverse effects by suppress ing L-type calcium channels in the heart. In sections of the spinal cord, the non-volatile anaesthetics pentobarbital, thiopental and propofol reduced excitability of sensorimotor neurons by suppressing plateau potentials mediated by L-type calcium channels. This effect was independent of GABA(A) receptor potentiation but occurred in an overlapping concentration range. Therefore, the suppressive effect of non-volatile anaesthetics on L-type calcium channels can contribute to the reduction of spinal sensorimotor activity during anaesthesia. The results support the idea that general anaesthesia is achieved through several mechanisms and suggest that procedures for anaesthesia may be improved by combining selective agents for each mechanism in optimal concentrations.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1999

Oscillatory interaction between dorsal root excitability and dorsal root potentials in the spinal cord of the turtle.

The response to dorsal root stimulation, at one to two times threshold, was investigated in the isolated cervical enlargement of the turtle spinal cord. At frequencies near 10 Hz the synaptic response in motoneurons and the cord dorsum potential, after an initial lag time, oscillated in amplitude with a period of more than 1 s. The mono- and polysynaptyic postsynaptic response in motoneurons, the pre- and postsynaptic component of the cord dorsum potential and the dorsal root potential oscillated in synchrony. These oscillations were only observed with stimulus frequencies in the range 9-11 Hz. The oscillating response could only be evoked from stimulus sites to which dorsal root potentials were conducted from the spinal cord (2-3 mm). At more distant stimulus sites cyclic variations in amplitude of the cord dorsum potential and the synaptic response in motoneurons were not observed. During an oscillating spinal response to a stimulus train in one dorsal root filament, the response evoked by a stimulus in another short filament (2-3 mm) from the same root varied in amplitude with the induced oscillation. The spinal response to a stimulus in a longer filament (i.e. more than 3 mm) did not oscillate. It is argued that the oscillating responses described rely on interactions between distributed elements rather than on unit oscillators. We also show that primary afferent transmission is unaffected by the substantial variations in dorsal root potentials during oscillations.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1999

Ca(2+)-activated nonselective cationic current (I(CAN)) in turtle motoneurons.

The presence of a calcium-activated nonspecific cationic (CAN) current in turtle motoneurons and its involvement in plateau potentials, bistability, and wind-up was investigated by intracellular recordings in a spinal cord slice preparation. In the presence of tetraethylammonium (TEA) and tetrodotoxin (TTX), calcium action potentials evoked by depolarizing current pulses were always followed by an afterdepolarization associated with a decrease in input resistance. The presence of the afterdepolarization depended on the calcium spike and not on membrane potential. Replacement of extracellular sodium by choline or N-methyl-D-glucamine (NMDG) reduced the afterdepolarization, confirming that it was mediated by a CAN current. Plateau potentials and wind-up were evoked in response to intracellular current pulses in the presence of agonist for different metabotropic receptors. Replacement of extracellular sodium by choline or NMDG did not abolish the generation of plateau potentials, bistability, or wind-up, showing that Na(+) was not the principal charge carrier. It is concluded that plateau potentials, bistability and wind-up in turtle motoneurons do not depend on a CAN current even though its presence can be detected.

Action Potentials↗
PubMed1998

Chemical and electrical stimulation induce rhythmic motor activity in an in vitro preparation of the spinal cord from adult turtles.

Bath application of N-Methyl-D-aspartate (NMDA) and serotonin induced rhythmic activity in hindlimb motoneurons in an isolated spinal cord preparation from adult turtles. Subthreshold concentrations of NMDA and serotonin accompanied by stimulation of the dorsal funiculus also induced rhythmic activity. The induced activity in motoneurons and ventral roots displayed characteristics which resemble that of locomotion. This activity could be evoked in as few as three segments (D8-D10) of the lumbar enlargement isolated from the rest of the spinal cord. The existence of intrinsic oscillations in single neurons was revealed in the presence of tetrodotoxin. Our findings introduce a new in vitro preparation in which electrophysiological and pharmacological tools can be used with ease to study mechanisms of central pattern generation in a mature spinal motor network.

Animals↗
PubMed1998

Inhibitory control of plateau properties in dorsal horn neurones in the turtle spinal cord in vitro.

1. The role of inhibition in control of plateau-generating neurones in the dorsal horn was studied in an in vitro preparation of the spinal cord of the turtle. Ionotropic and metabotropic inhibition was found to condition the expression of plateau potentials. 2. Blockade of gamma-aminobutyric acid (GABAA) and glycine receptors by their selective antagonists bicuculline (10-50 microM) and strychnine (5-20 microM) enhanced the excitatory response to stimulation of the dorsal root and facilitated the expression of plateau potentials. 3. Bicuculline and strychnine also facilitated the generation of plateau potentials in response to depolarizing current pulses, suggesting the presence of tonic ionotropic inhibitory mechanisms in turtle spinal cord slices. 4. Activation of GABAB receptors also inhibited plateau-generating neurones. The selective agonist baclofen (5-50 microM) inhibited wind-up of the response to repeated depolarizations induced synaptically or by intracellular current pulses. 5. Baclofen reduced afferent synaptic input. This effect was not affected by bicuculline or strychnine and was blocked by the selective GABAB receptor antagonist 2-hydroxysaclofen (2-OH-saclofen, 100-400 microM). 6. Postsynaptically, baclofen inhibited plateau properties. Activation of GABAB receptors produced a hyperpolarization (7.0 +/- 0.5 mV, mean +/- S.E.M., n = 29) with an associated decrease in input resistance (22.7 +/- 3.1%, n = 24). These effects were blocked by extracellular Ba2+ (1-2 mM). 7. When the baclofen-induced hyperpolarization and shunt were compensated for by adjusting the bias current and the strength of the stimulus, baclofen still inhibited generation of plateau potentials. Wind-up and after-discharges were also inhibited by baclofen. These effects remained in the presence of tetrodotoxin (1 microM) and were antagonized by 2-OH-saclofen. 8. The inhibition of plateau properties was observed even when the baclofen-induced hyperpolarization and shunt were blocked by Ba2+ and when potassium channels were blocked by Ba2+ (3 mM), tetraethylammonium (TEA, 15 mM) and apamin (0.25-0.5 microM). The baclofen-sensitive component of the plateau potential was reduced by nifedipine (10 microM), suggesting a modulation of postsynaptic L-type Ca2+ channels. 9. We suggest that inhibitory regulation of plateau properties plays a role in somatosensory processing in the dorsal horn. The inhibitory control of wind-up and after-discharges may be particularly significant in physiological and therapeutic control of central sensitization to pain.

Animals↗
PubMed1998

Transmitter regulation of plateau properties in turtle motoneurons.

In motoneurons, generation of plateau potentials is promoted by modulators that block potassium channels. In voltage-clamp experiments with triangular voltage ramp commands, we show that cis-(+/-)-1-aminocyclopentane-1, 3-dicarboxylic acid (cis-ACPD) and muscarine promote the generation of plateau potentials by increasing the dihydropyridine sensitive inward current, by increasing the input resistance, and by depolarizing the resting membrane potential. Type I metabotropic glutamate receptors (mGluR I) mediate the effects of cis-ACPD. Baclofen suppresses generation of plateau potentials by decreasing the dihydropyridine sensitive inward current, by decreasing the input resistance, and by hyperpolarizing the resting membrane potential. These results suggest that membrane properties of motoneurons are continuously modulated by synaptic activity in ways that may have profound effects on synaptic integration and pattern generation.

Animals↗
PubMed1998

NMDA-Induced intrinsic voltage oscillations depend on L-type calcium channels in spinal motoneurons of adult turtles.

NMDA-induced intrinsic voltage oscillations depend on L-type calcium channels in spinal motoneurons of adult turtles. J. Neurophysiol. 80: 3380-3382, 1998. In a slice preparation from adult turtles, bath-applied N-methyl-D-aspartate (NMDA) induced rhythmic activity in spinal motoneurons. The underlying intrinsic oscillation in membrane potential was revealed in the presence of tetrodotoxin (TTX). NMDA-induced rhythmicity, in the presence or absence of TTX, was abolished or reduced by NMDA receptor antagonists and by three different classes of antagonists for L-type calcium channels. It is suggested that both NMDA receptor channels and L-type calcium channels contribute to NMDA-induced intrinsic oscillations in mature spinal motoneurons.

Animals↗
PubMed1997

Metabotropic synaptic regulation of intrinsic response properties of turtle spinal motoneurones.

1. The effect of a brief train of electric stimuli in the dorsolateral funiculus on the intrinsic response properties of turtle motoneurones was investigated in transverse sections of the spinal cord in vitro. 2. Even when glutamatergic, GABAergic and glycinergic ionotropic synaptic transmission was blocked by antagonists of AMPA, NMDA, glycine and GABA receptors, dorsolateral funiculus (DLF) stimulation induced a facilitation of plateau potentials during current clamp and the underlying inward current in voltage clamp. This facilitation lasted more than 10 s. 3. The plateau potential and the facilitation by DLF stimulation was absent in the presence of 10 microM nifedipine. The DLF-induced facilitation was reduced by antagonists of 5-HT1A, group 1 metabotropic glutamate receptors and muscarine receptors. 4. These findings suggest that the intrinsic properties of spinal motoneurones are dynamically regulated by afferent synaptic activity. These afferents can be of spinal and extraspinal origin. Continuous regulation of intrinsic response properties could be a mechanism for motor flexibility.

Animals↗