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J Hounsgaard

Publications and source records attributed to J Hounsgaard.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1997

Modulation of plateau properties in dorsal horn neurones in a slice preparation of the turtle spinal cord.

1. Modulation of plateau properties in dorsal horn neurones was studied in a transverse slice preparation of the spinal cord of the turtle. In plateau-generating neurones high frequency stimulation of the ipsilateral dorsal root (10-20 Hz, 0.5-2 min) produced a slow depolarization (2.9 +/- 0.6 mV, mean +/- S.E.M.; n = 6) and enhanced the properties mediated by dihydropyridine-sensitive Ca2+ channels. The tetanic stimulus facilitated wind-up and after-discharges even when fast synaptic transmission was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10-20 microM), (+/-)-2-amino-5-phosphonopentanoic acid (AP5, 100 microM), bicuculline (10-20 microM) and strychnine (5-20 microM). 2. Application of cis-(+/-)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD, 10-50 microM) produced a slow depolarization (5.9 +/- 0.5 mV, n = 21) accompanied by an increase in input resistance (28.8 +/- 5.1%, n = 12). 3. ACPD increased the excitability by facilitating the plateau properties. In the presence of tetrodotoxin (TTX, 1 microM) a lower threshold and a slower decay of the plateau potential were observed. These effects resulted in facilitation of wind-up and prolonged after-discharges. 4. All ACPD-induced effects were blocked by alpha-methyl-4-carboxyphenylglycine (MCPG, 0.5-1 mM), a selective antagonist of metabotropic glutamate receptors. The selective agonist for the type I metabotropic glutamate receptor ((RS)-3,5-dihydrophenylglycine (DHPG, 50 microM)) reproduced all the effects of ACPD. 5. Application of a supposed neuromodulator, substance P (1-2 microM) produced a transient depolarization (4 +/- 0.6 mV) lasting 4-6 min during continued application of substance P. Variable effects on the input resistance were observed, a slight increase (12 +/- 2%) being the most frequent. In 61% of the cells, substance P induced a clear increase in excitability with no detectable change in input resistance or membrane potential. 6. The effects of substance P on plateau properties were indistinguishable from those produced by ACPD. Unlike the transient depolarization, the facilitation of the plateau properties persisted in the presence of the agonist. 7. The substance P-induced facilitation of the plateau potential was blocked by GR 82334 (5-10 microM), a selective NK-1 tachykinin-receptor antagonist, and was not affected by MEN 10376 (2 microM), a selective NK-2 antagonist. 8. The facilitation of plateau properties produced by dorsal root stimulation was also reduced by antagonists of metabotropic glutamate receptors and NK-1 tachykinin receptors. 9. We propose that modulation of postsynaptic plateau properties in dorsal horn neurones by activation of type I metabotropic glutamate receptors and NK-1 tachykinin receptors is involved in processing nociceptive information.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1997

Electrotonic measurements by electric field-induced polarization in neurons: theory and experimental estimation.

We present a theory for estimation of the dendritic electrotonic length constant and the membrane time constant from the transmembrane potential (TMP) induced by an applied electric field. The theory is adapted to morphologically defined neurons with homogeneous passive electric properties. Frequency characteristics and transients at the onset and offset of the DC field are considered. Two relations are useful for estimating the electrotonic parameters: 1) steady-state polarization versus the dendritic electrotonic length constant; 2) membrane time constant versus length constant. These relations are monotonic and may provide a unique estimate of the electrotonic parameters for 3D-reconstructed neurons. Equivalent tip-to-tip electrotonic length of the dendritic tree was estimated by measuring the equalization time of the field-induced TMP. For 11 turtle spinal motoneurons, the electrotonic length from tip to tip of the dendrites was in the range of 1-2.5 lambda, whereas classical estimation using injection of current pulses gave an average dendrite length of 0.9-1.1 lambda. For seven ventral horn interneurons, the estimates were 0.7-2.6 lambda and 0.6-0.9 lambda, respectively. The measurements of the field-induced polarization promise to be a useful addition to the conventional methods using microelectrode stimulation.

Animals↗
PubMed1997

Detection of a membrane shunt by DC field polarization during intracellular and whole cell recording.

Lower input resistance with intracellular recording, rather than with whole cell recording, usually has been ascribed to a shunt produced by penetration injury. An alternative explanation is a higher input resistance during whole cell recording due to wash-out of cytoplasmatic substances. We have used neuronal polarization at the onset and termination of an applied electric field for shunt detection. An analytical expression was derived for field-induced polarization in a shunted ohmic cable. When the shunt is negligible, the transient response to a step in DC field decays much faster than the response to current injected through the recording electrode. In the case of a significant shunt an over- and undershoot of the transmembrane potential appear at the shunted end when the field is switched on and off. Over- and undershoot decay with the same slowest time constant as the response to injected current. The results for the cable are generalized for nonuniform fields and arbitrary branching neurons with homogeneous membrane. The field effect was calculated for two reconstructed neurons with different branching pattern. The calculations confirmed the theoretical inferences. The field polarization can be used for shunt detection. The theory was checked experimentally in 18 ventral neurons in transverse slices of the turtle spinal cord. In seven neurons, field-induced under- and overshoots were observed when sharp electrodes were used. This indicates the presence of an injury shunt. In the remaining 11 neurons, however, there were no under- or overshoots, indicating that a shunt is not always induced. When patch electrodes were used, the seal quality was checked by inducing a spike with a strong field stimulus before and after the rupture of the membrane. When the threshold field strength for spike initiation was not changed by membrane rupture, under- and overshoots were not observed. This was taken to indicate a good seal. In such recordings under- and overshoots were observed when a shunt was induced by local application of glycine. The fast and monotonic response to weak field stimulation suggests homogeneous electric properties of the soma-dendritic membrane when active conductances are not recruited. We propose using polarization by weak DC fields to ensure the quality of recordings with sharp and whole cell electrodes and for checking the ohmic homogeneity of the membrane. These controls are particularly important for evaluation of electrotonic parameters.

Animals↗
PubMed1997

Depolarization-induced facilitation of a plateau-generating current in ventral horn neurons in the turtle spinal cord.

Plasticity at the neuronal level commonly involves use-dependent changes in strength of particular synaptic pathways or regulation of postsynaptic properties by modulatory transmitters. Here we analyze a novel form of short-term plasticity mediated by use-dependent facilitation of postsynaptic responsiveness. Using current- and voltage-clamp recordings, we found that all spinal ventral horn neurons able to generate plateau potentials showed depolarization-induced facilitation of the underlying inward current. Facilitation was noticeable when the neurons were depolarized to more than -50 mV at intervals <4 s. When stimulation with fast triangular voltage ramps was used, the inward current activated at a less depolarized potential during the second ramp. The inward current and facilitation was eliminated by nifedipine, a selective antagonist of L-type calcium channels. Depolarization-induced facilitation of low-voltage-activated L-type calcium channels is suggested to be the underlying mechanism. It is noted that facilitation occurs on a time scale compatible with a role in phasic motor activity.

Animals↗
PubMed1996

Plateau-generating neurones in the dorsal horn in an in vitro preparation of the turtle spinal cord.

1. In transverse slices of the spinal cord of the turtle, intracellular recordings were used to characterize and analyse the responses to injected current and activation of primary afferents in dorsal horn neurones. 2. A subpopulation of neurones, with cell bodies located laterally in the deep dorsal horn and dendrites radiating towards the pial surface, was distinguished by the ability to generate plateau potentials. Activation of the plateau potential by a suprathreshold depolarizing current pulse produced an increasing firing frequency during the first few seconds and a sustained after-discharge. 3. The plateau potential was assumed to be mediated by L-type Ca2+ channels since it was blocked by Co2+ (3 mM) and nifedipine (10 microM) and enhanced by Bay K 8644 (0.5-2 microM). 4. The threshold for activating the plateau potential declined during the first few seconds of depolarization. The decline in threshold gradually subsided over 3-10 s after repolarization. 5. Frequency potentiation of the plateau potential contributed to wind-up of the response to depolarizing current pulses and primary afferent stimuli repeated at frequencies higher than 0.1-0.3 Hz. 6. The sustained after-discharge mediated by the plateau potential was curtailed by a slow after-hyperpolarization (sAHP) evoked by strong depolarizations. The relative strength of the plateau potential and sAHP varied among cells. In some cells the plateau potential and sAHP interacted to produce damped oscillations upon depolarization. The sAHP was mediated by both apamin and tetraethylammonium (TEA)-sensitive K+ channels. 7. Our findings suggest that basic properties of sensory integration may reside with the specialized intrinsic response properties of particular subtypes of neurones in the dorsal horn.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1996

Burst-generating neurones in the dorsal horn in an in vitro preparation of the turtle spinal cord.

1. In transverse slices of the spinal cord of the turtle, intracellular recordings were used to characterize and analyse the responses to injected current and activation of primary afferents in dorsal horn neurones. 2. A subpopulation of neurones, with cell bodies located centrally in the dorsal horn, was distinguished by the ability to generate a burst response following a hyperpolarization from rest or during a depolarization from a hyperpolarized holding potential. The burst response was inactivated at the resting membrane potential. 3. The burst response was mediated by a low threshold Ca2+ spike assumed to be mediated by T-type Ca2+ channels since it resisted tetrodotoxin and was blocked by 3 mM Co2+ or 100-300 microM Ni2+ and resembled the low threshold spike (LTS) described elsewhere. 4. Some burst-generating cells also displayed plateau potentials mediated by L-type Ca2+ channels. In these cells the burst following a hyperpolarizing current pulse, applied from the resting membrane potential, facilitated the activation of the plateau potential. Wind-up of the plateau potential was produced when the hyperpolarizing pulse generating the burst was repeated at 0.1-0.3 Hz or faster. 5. The burst response and the underlying low threshold Ca2+ spike were activated synaptically by primary afferent stimuli in a voltage range hyperpolarized from the resting membrane potential. 6. Cells with bursts were morphologically distinguishable from cells with bursts and plateau properties. 7. Our findings in this and the preceding paper show that the intrinsic response properties of particular subtypes of neurones in the dorsal horn have a profound influence on the amplitude and time course of the responses mediated by primary afferent fibres. We predict that these postsynaptic properties are probable targets for synaptic modulation.

Action Potentials↗
PubMed1996

Monosynaptic connections between primary afferents and giant neurons in the turtle spinal dorsal horn.

This paper reports the occurrence of monosynaptic connections between dorsal root afferents and a distinct cell type-the giant neuron-deep in the dorsal horn of the turtle spinal cord. Light microscope studies combining Nissl stain and transganglionic HRP-labeling of the primary afferents have revealed the occurrence of axosomatic and axodendritic contacts between labeled boutons and giant neurons. The synaptic nature of these contacts has been confirmed by use of electron microscope procedures involving the partial three-dimensional reconstruction of identified giant neurons. Intracellular recording in spinal cord slices provided functional evidence indicating the monosynaptic connections between dorsal root afferents and giant neurons. The recorded neurons were morphologically identified by means of biocytin injection and with avidin conjugates. Electrical stimulation of the ipsilateral dorsal roots evoked synaptic responses with short, fixed latencies (1.6-5.6 ms), which remained unchanged at high frequencies (10 Hz). Excitatory polysynaptic potentials were also observed. By means of pharmacological procedures the short-latency response was dissected in two components: one insensitive to tetrodotoxin, the other abolished by the drug. The toxin-resistant component was presumed to be sustained by small-diameter C fibers. The synaptic response was mainly mediated by the glutamate-AMPA receptor subtype; however, a small component mediated by NMDA receptor was also present.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1996

Fast Na+ spike generation in dendrites of guinea-pig substantia nigra pars compacta neurons.

Electric fields were applied to study the regenerative properties of substantia nigra pars compacta neurons in guinea-pig brain slices. Two types of spikes, of high or low amplitude, were generated in both the soma-hyperpolarizing and the soma-depolarizing directions of the field. The different sensitivity of the spikes to somatic polarization suggested that the high-amplitude spikes were generated near the cell body, whereas the low-amplitude spikes were generated at a distance from the soma. Application of tetrodotoxin or intracellular injection of QX 314 abolished both types of spike. The spikes were not inhibited in the presence of glutamate receptor antagonists or during Ca2+ channel blockade. Blockers of gap junctional conductance (sodium propionate, octanol and halothane) did not affect the field-induced spikes. The spike generation was highly sensitive to changes in membrane conductance induced by current injection in the soma or by external field application. The ability of a conditioning field stimulation to affect the spike generation in different neuronal compartments suggested that a transient outward current was generated in the dendrites. The field-induced spikes were facilitated by synaptic stimulation and, in some neurons, low-amplitude spikes were generated by synaptic potentials in the absence of field application. These results suggest that channels responsible for Na+ spike generation reside in the dendrites, and are influenced by spatially distributed voltage-dependent K+ currents and by synaptic input.

Anesthetics, Local↗
PubMed1996

Multiple actions of iontophoretically applied serotonin on motorneurones in the turtle spinal cord in vitro.

The effects of focal activation of serotonergic receptors in motorneurones were investigated in a slice preparation of the turtle spinal cord. The test response to glutamate evoked from a dendrite by iontophoresis was attenuated by serotonin or 8-hydroxy-dipropyl-aminotetralin (8-OH-DPAT) applied from an independent pipette within 100 microns of the glutamate pipette. This effect was not associated with a conductance change and did not affect glutamate responses evoked more than 100 microns from the serotonin pipette. The effect of serotonin was not reproduced by H+ ions. Plateau potentials were rarely facilitated by serotonin when applied in the dendritic field. Plateau potentials were readily facilitated by serotonin applied near the soma. This effect was preceded by attenuation of the slow after-hyperpolarization following an action potential. Applied near the soma, serotonin inhibited the response to a depolarizing current pulse of moderate strength and enhanced the response to a current pulse of high amplitude. These effects were associated with a conductance increase. We conclude that serotonin has spatially diverse effects on motorneurones.

Animals↗
PubMed1994

Spatial integration of local transmitter responses in motoneurones of the turtle spinal cord in vitro.

1. Integration of responses to local activation of transmitter receptors in the dendrites of motoneurones was investigated in a slice preparation of the turtle spinal cord. Membrane-active substances were applied from up to three independent iontophoresis electrodes during intracellular recording from the cell body. 2. Responses to glutamate could be evoked from dendrites closer than 20 microns from the tip of the glutamate electrode. The effects of other substances were more widespread. 3. In normal medium the configuration of a glutamate response was affected by time-dependent anomalous rectification. In the presence of muscarine the sum of glutamate responses from two different dendrites recruited a voltage-sensitive plateau potential. 4. The response to glutamate from one dendrite could be attenuated by local application of gamma-aminobutyric acid (GABA) without effects on soma conductance or glutamate responses from other dendrites. 5. The response to glutamate from one dendrite could be selectively enhanced by local application of tetraethylammonium (TEA) or N-methyl-D-aspartate (NMDA) without effects on soma conductance or glutamate responses from other dendrites. 6. NMDA could convert a tonic glutamate response from one dendrite into a phasic response without affecting the configuration of glutamate responses from other dendrites. 7. The effects of TEA and NMDA were facilitated by depolarization and reduced by hyperpolarization. 8. We conclude that the cable structure of motoneurones and the distribution of synapses and voltage-sensitive ion channels provide relative autonomy to non-linear synaptic processing and modulation in confined dendritic regions.

Animals↗
PubMed1994

Direct monitoring of dopamine and 5-HT release in substantia nigra and ventral tegmental area in vitro.

Fast-scan cyclic voltammetry with carbon fibre microelectrodes was used to detect endogenous dopamine (DA) and 5-hydroxytryptamine (5-HT) release from three distinct regions of guinea-pig mid-brain in vitro: rostral and caudal substantia nigra (SN) and the ventral tegmental area (VTA). Previous electrophysiological studies have demonstrated that cells of the caudal SN and the VTA have similar characteristics, whereas cells in the rostral SN have distinctly different properties. In the present study, we confirmed that each region has tyrosine hydroxylase-positive neurons and determined, using high-performance liquid chromatography, that DA levels were similar in rostral and caudal SN, but lower in SN than in VTA. In each region, application of veratrine, which was shown by intracellular recordings to have a reversible depolarising action, evoked a signal attributable to DA and distinguishable from that of 5-HT. Release signals were monitored every 250 ms with a spatial resolution of less than 50 microns.l DA release was calcium-dependent and was not detectable in a catecholamine-poor area such as the cerebellum, or in mid-brain tissue pre-treated with reserpine. Within the normal mid-brain, the amount of DA released was correlated with tissue content in that it was higher in the VTA than in either region of SN. It is concluded that DA released from somato-dendritic parts of mid-brain neurons exhibits site-specific variation. This is the first report of direct monitoring of DA and 5-HT release from these regions with in situ electrodes and demonstrates the utility of fast-scan cyclic voltammetry to investigate the mechanisms and possible non-classical functions of somato-dendritic DA release.

Animals↗
PubMed1994

Short-term plasticity in turtle dorsal horn neurons mediated by L-type Ca2+ channels.

Windup--the gradual increase of the response--of dorsal horn neurons to repeated activation of primary afferents is an elementary form of short-term plasticity that may mediate central sensitization to pain. In deep dorsal horn neurons of the turtle spinal cord in vitro we report windup of the response to repeated depolarizing current pulses as well as to repeated stimulation of the ipsilateral dorsal root. We found both forms of windup to be mediated by a depolarizing potential produced by increasing activation of postsynaptic L-type Ca2+ channels. These results suggest a central role for intrinsic postsynaptic properties in nociceptive plasticity and for L-type Ca2+ channels as a promising target for therapeutic intervention.

Action Potentials↗
PubMed1993

Calcium spikes and calcium plateaux evoked by differential polarization in dendrites of turtle motoneurones in vitro.

1. The ability of dendrites in turtle motoneurones to support calcium spikes and calcium plateaux was investigated using differential polarization by applied electric fields. 2. Electric fields were generated by passing current through transverse slices of the turtle spinal cord between two plate electrodes. The linear extracellular voltage gradient generated by the field implied that the tissue was ohmic and homogeneous. 3. The transmembrane potential at the cell body of motoneurones was measured as the voltage difference between an intracellular and an extracellular microelectrode. 4. In normal medium an applied field induced synaptic activity as well as intrinsic polarization of motoneurones. Synaptic activity was suppressed by tetrodotoxin (TTX, 1 microM). 5. In the presence of TTX and tetraethylammonium (TEA, 1-5 mM), applied fields evoked multicomponent Ca2+ spikes in both the soma-hyperpolarizing and soma-depolarizing direction of the field. The different components of Ca2+ spikes were discrete and additive. High amplitude components had higher threshold and faster time course and were followed by larger after-hyperpolarizations, than low amplitude components. The frequency of field-evoked regenerative responses was relatively insensitive to somatic bias current. 6. TTX-resistant Ca(2+)-mediated plateau potentials promoted by apamin were evoked by differential polarization in both the soma-depolarizing and soma-hyperpolarizing direction. 7. It is concluded that Ca2+ channels responsible for Ca2+ spikes and Ca2+ plateaux are present in dendrites of spinal motoneurones of the turtle.

Animals↗
PubMed1992

Electrophysiological localization of distinct calcium potentials at selective somatodendritic sites in the substantia nigra.

The dendrites of dopaminergic neurons in the substantia nigra play a pivotal role in the neurochemical homeostasis of the nucleus. It is conceivable therefore that the cell body and dendrites of these nigral neurons possess distinct and independent electro-responsive features. By means of differential polarization through applied electric fields, the cell body and dendrites have been activated in effective isolation during intracellular recordings from pars compacta neurons in the substantia nigra in vitro. In one class of neurons, which discharge in a "phasic" fashion and are located in the rostral substantia nigra, the dendrites are shown to be the origin of classic low-threshold and high-threshold type calcium potentials: indeed the high-threshold conductance appears to be exclusively dendritic. By contrast, in a second, more caudally located cell type, which discharges rhythmically, a high-threshold calcium spike is located principally in the cell body. The differential localization of these calcium conductances in sub-populations of neurons is likely to determine the functions for the calcium responses in each type of neuron, and moreover highlight the dendrites as dynamic and selective components in the physiology of the substantia nigra. The presence, for example, of the high-threshold calcium conductance in the dendrites of only one class of neuron suggests that this sub-population plays a prominent role in non-classical phenomena of dendritic release of a variety of chemical mediators.

Animals↗
PubMed1989

Excitatory synaptic responses in turtle cerebellar Purkinje cells.

1. Climbing fibre responses (CFRs) and parallel fibre responses (PFRs) in Purkinje cells have been analysed in intracellular recordings obtained at various levels from cell body to terminal dendrites in the turtle cerebellum in vitro. 2. With increasing stimulus intensity, the PFR recorded in distal dendrites displayed an early regenerative component which was graded at rest and at hyperpolarized membrane potentials, but was all-or-none at depolarized membrane potentials. 3. The all-or-none component had the same characteristics as Ca2+ spikes triggered by passing depolarizing current through the recording electrode. 4. The repolarizing phase of the PFR had a fast component enhanced by depolarization and diminished by hyperpolarization. 5. In the mid-molecular layer the PFR also included a plateau component which was increasingly prolonged by depolarization and abolished by hyperpolarization. 6. CFRs recorded in the soma had a plateau component, prolonged by local depolarization and abolished by local hyperpolarization. 7. The CFR in distal dendrites included a regenerative component. In some cells this component appeared in an all-or-none manner with local depolarization. In other cells it was smoothly graded with local polarization. 8. In mid-molecular records the CFR was prolonged by local depolarization and presumably electrotonically affected by the configuration of the response more distally and proximally in the cell. 9. It is concluded that excitatory synaptic responses in Purkinje cells include a regenerative Ca2+-mediated spike component in the spiny dendrites and a plateau component located in the proximal dendrites and/or the cell body. It is shown that both responses are modulated in configuration by the local membrane potential. In the spiny dendrites activation and inactivation of the transient hyperpolarizing potential appear to govern the Ca2+ influx during the CFR.

Action Potentials↗