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J Hounsgaard

Publications and source records attributed to J Hounsgaard.

At least 19 recordsLinked to original sources
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↗
PubMed1989

Synaptic control of excitability in turtle cerebellar Purkinje cells.

1. In turtle Purkinje cells in vitro successive climbing fibre responses (CFRs) gradually induced a hyperpolarization that persisted with maintained stimulation and decayed over minutes after climbing fibre stimulation was terminated. 2. The rate of development and the amplitude of this long-lasting hyperpolarization (LHP) increased with the frequency of CFRs. 3. The LHP was also induced by Ca2+ spikes evoked by current injection but not by Na+ spikes. The LHP was blocked by Co2+ but not by tetrodotoxin and could not be explained solely by an increased K+ conductance. 4. Depolarizing current during a train of CFRs enhanced the regenerative component of CFRs and promoted the LHP. Hyperpolarizing current during the stimulus train reduced the regenerative component of CFRs and attenuated the resulting LHP. 5. In the range of membrane potentials attained at different levels of climbing fibre activity the regenerative component of CFRs varied from being dominant at very low stimulus frequency (0.1 s-1) to being inconspicuous at high stimulus frequency (10 s-1). 6. It is concluded that successive CFRs induce a Ca2+-dependent, long-lasting hyperpolarization. The magnitude of the hyperpolarization is regulated by the rate of CFRs and by the voltage- and frequency-dependent configuration of each individual CFR. 7. The active, non-synaptic properties of turtle Purkinje cells make the Ca2+ influx during climbing fibre responses prone to regulation by on-going synaptic activity and by the after-effects of synaptic activity on a time scale of minutes. We suggest that this arrangement may enhance the capacity and complexity of spatial and temporal synaptic integration in Purkinje cells.

Action Potentials↗
PubMed1989

Serotonin-induced bistability of turtle motoneurones caused by a nifedipine-sensitive calcium plateau potential.

1. The effect of serotonin on the firing properties of motoneurones was studied in transverse sections of the adult turtle spinal cord in vitro with intracellular recording techniques. 2. In normal medium, turtle motoneurones adapt from an initial high frequency to a low steady firing during a depolarizing current pulse. In the presence of serotonin (4-100 microM) motoneurones responded with accelerated firing and a frequency jump during a depolarizing current pulse followed by an after-depolarization outlasting the stimulus. From a depolarized holding potential motoneuronal activity was shifted between two stable states by brief depolarizing and hyperpolarizing current pulses. As an expression of this bistable firing behaviour, the frequency-current relation in response to a triangular current injection was counter-clockwise in serotonin while clockwise in normal medium. 3. The delay to onset of the frequency jump was shortened as the amplitude of the activation pulse was increased. From a positive holding potential the after-depolarization exceeded spike threshold and its duration increased with an increase in steady bias current. The effect of serotonin on turtle motoneurones could be blocked by methysergide (10 microM). 4. When action potentials were depressed by tetrodotoxin, a voltage-dependent, non-inactivating plateau potential, intrinsic to the motoneurone, was revealed. Activation of this voltage plateau provides the motoneurones with two stable states of firing. The apparent input resistance was 2-4-fold lower during the plateau than at rest. 5. The serotonin-induced plateau potential was Ca2+-dependent and was blocked when Ca2+ was replaced by either Co2+ (3 mM) or Mn2+ (3 mM). 6. The Ca2+ plateau was blocked by nifedipine (1-15 microM). 7. Serotonin reduced the slow after-hyperpolarization following action potentials. The change in balance between inward and outward currents seems to be sufficient to reveal the plateau response. 8. Although a small plateau response was induced by Bay K 8644 (1-15 microM), this L-channel agonist could not reproduce the pronounced effect of serotonin. 9. It is concluded that serotonin induces a Ca2+-dependent and nifedipine-sensitive plateau potential in turtle motoneurones primarily by reducing a K+-current responsible for the slow after-hyperpolarization.

Animals↗
PubMed1988

Response properties of motoneurones in a slice preparation of the turtle spinal cord.

1. Motoneurones in transverse sections of the turtle spinal cord were investigated in vitro with intracellular recording techniques. 2. Turtle motoneurones had a resting membrane potential of -60 to -80 mV, spike height of 90-110 mV and were able to maintain rhythmic firing during depolarization. In agreement with the size variation of the cells the input resistance and time constant ranged from 18 M omega and 12 ms to 55 M omega and 61 ms. 3. The active response properties of motoneurones included time-dependent inward rectification in response to hyperpolarizing current pulses. The action potential had an initial segment (IS) and a soma-dendritic (SD) component and was followed by a fast and a slow after-hyperpolarization (AHP) with different sensitivity to membrane potential. 4. The relation between firing rate and injected current was sigmoid when determined for the first few interspike intervals during depolarizing current pulses. Adaptation was biphasic with an early phase lasting 0.5-1 s and a late phase lasting 10-20 s. 5. The ionic conductances responsible for the active membrane properties included a tetrodotoxin (TTX)-sensitive Na+ conductance generating the action potential and a Ca2+ conductance transiently activated during the action potential. A tetraethylamonium (TEA)-sensitive K+ conductance was responsible for spike repolarization and the fast AHP. A Ca2+-dependent K+ conductance, blocked by Mn2+ and apamin, accounted for only part of the slow AHP. The time-dependent inward rectification was selectively blocked by extracellular Cs+ at concentrations below 1 mM. 6. The results show that the response properties of spinal motoneurones of the turtle are closely similar to those known from mammals in vivo. The experiments confirm and extend the identification of the ionic conductances underlying the active response properties of spinal motoneurones.

Action Potentials↗
PubMed1988

Calcium conductance and firing properties of spinal motoneurones in the turtle.

1. The contribution of Ca2+ conductance to the firing properties of motoneurones was investigated in transverse slices of the turtle spinal cord. 2. In the presence of tetrodotoxin (TTX), tetraethylamonium (TEA) in low extracellular concentration (less than 5 mM) promoted Ca2+ spikes. In higher concentrations of TEA, a suprathreshold depolarizing current pulse was followed by an after-discharge of Ca2+ spikes riding on a Ca2+ plateau potential. 3. The Ca2+-dependent plateau was also promoted by Cs+, 4-aminopyridine (4-AP) and apamin. However, Ca2+ spikes during plateaux were an order of magnitude faster when promoted by Cs+ or 4-AP rather than TEA, and apamin did not promote Ca2+ spikes at all. 4. Ca2+ plateaux but not Ca2+ spikes were blocked by nifedipine. 5. In normal medium all effects of the transient Ca2+ influx during action potentials were attributable to its influence on the slow after-hyperpolarization. The nifedipine-sensitive, sustained Ca2+ influx was expressed exclusively as plateau potentials and only under conditions of reduced K+ current. 6. It is concluded that the transient and the sustained Ca2+ fluxes in spinal motoneurones are curtailed by different K+ conductances. The two Ca2+ responses are suggested as being mediated by two different types of Ca2+ channels.

4-Aminopyridine↗
PubMed1988

Intrinsic determinants of firing pattern in Purkinje cells of the turtle cerebellum in vitro.

1. The intrinsic response properties of turtle Purkinje cells and the underlying conductances have been investigated with intradendritic and intrasomatic recordings in a slice preparation. 2. The active generation site for fast Na+ spikes was confined to the soma and for slow Ca2+ spikes to the dendrites. The configuration and generation of Ca2+ spikes was more affected by the level of extracellular K+ than were Na+ spikes. 3. Sodium spikes had a lower threshold than Ca2+ spikes at all recording sites. Sodium spike firing was abruptly initiated during depolarizing current pulses and the spike frequency increased from an early minimum to a higher steady-state level over a period of seconds or until the occurrence of Ca2+ spikes. Calcium spikes were always delayed by at least 100 ms from the onset of a depolarizing current pulse from rest. 4. The abrupt onset of Na+ spike firing was due to a tetrodotoxin-sensitive plateau potential. The phase of accelerating firing frequency and the delayed occurrence of Ca2+ spikes was due to a transient hyperpolarization activated by depolarization from rest or from more negative membrane potentials. The transient hyperpolarization was inactivated by depolarized holding potentials and was most probably generate by a rapidly inactivating K+ channel. 5. It is concluded that turtle Purkinje cells display the basic firing properties and underlying conductances known from Purkinje cells of other vertebrates. In turtle Purkinje cells Ca2+ spikes are actively generated in spiny dendrites and it is suggested that spiny dendrites rather than branch points are 'hot spots'. 6. The transient hyperpolarization, not previously described in Purkinje cells, seems particularly important for regulating Ca2+-dependent excitability.

Action Potentials↗
PubMed1988

Effects of electric fields on transmembrane potential and excitability of turtle cerebellar Purkinje cells in vitro.

1. Transmembrane potential (TMP) responses of Purkinje cells (PCs) in isolated turtle cerebellum to externally applied quasi-steady-state electric fields aligned with the dendritic axis were continuously measured using simultaneous intracellular and extracellular recording. TMP was obtained by subtraction of extracellular voltage fields from intracellular potential recorded at the same depth in the cerebellum. 2. The applied field changed the TMP with the polarity and amplitude dependent on the location on the PC membrane. This response at a given location increased linearly with external field up to a threshold level, beyond which active responses appeared. 3. The basic effect on TMP consisted of depolarization in the half of the dendrite towards which the fields were directed, and hyperpolarization in the other half. A pooled TMP depth-profile shows a steady increase in polarization from the middle of the molecular layer towards each end. This profile correlates with that predicted from previously proposed cable models, giving them empirical support for the first time. 4. Active responses were triggered by the field-induced depolarization. Tetrodotoxin (TTX)-sensitive action potentials arose with the primary depolarization in the somatic region. Notched, Ca2+-dependent action potentials arose with primary depolarization in the distal and mid-dendritic regions. 5. A TTX-sensitive voltage plateau was triggered by TMP-depolarization in the proximal region. It in turn activated Na+-spike trains. The frequency of spiking was proportional to the external field. At around 160 spikes/s, the Na+ spikes inactivated, and the TMP level rose to a more depolarized plateau. This latter plateau was also TTX-sensitive. 6. During depolarization of the distal dendritic region, sometimes a Ca2+-dependent plateau was observed. It appears to be associated with a small conductance increase. 7. Field-induced hyperpolarization suppressed local spiking and voltage plateaux, but remote Ca2+ spikes with reduced amplitude appeared in recordings from the proximal region. Similarly, in the distal region, low-amplitude, remote Na+ spikes and a Na+ plateau were observed superimposed on the hyperpolarizing baseline. The Na+ plateau apparently did not contribute to shunting of membrane currents in the distal dendrite. 8. The phase characteristics of the action potentials correlate with the modulation pattern noted in our extracellular study (Chan & Nicholson, 1986). Thus, the extracellular units ("giant spikes") were probably Na+ spikes activated in the soma and spread distally. Occasionally Ca2+ spikes, with a higher threshold, might also be activated to give dual-phase response.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1988

Bistability of alpha-motoneurones in the decerebrate cat and in the acute spinal cat after intravenous 5-hydroxytryptophan.

1. In the preceding paper (Crone, Hultborn, Kiehn, Mazieres & Wigström, 1988) it was shown that a short-lasting synaptic excitation ('on' stimulus) of extensor motoneurones (primarily triceps surae) in the decerebrate cat often resulted in a maintained excitability increase, which could be reset by a short-lasting inhibitory stimulus train ('off' stimulus). In the present experiments intracellular recording from triceps surae motoneurones and the electroneurogram (ENG activity) from triceps surae nerve branches were performed in parallel. 2. Sustained firing of individual triceps surae motoneurones was most often recorded in parallel with the maintained ENG activity following a synaptic 'on' stimulus. When the motoneurone was silenced, by a hyperpolarizing current through the microelectrode, there was no sign of on-going synaptic excitation during the maintained ENG activity following an 'on' stimulus. It was therefore suggested that voltage-dependent intrinsic properties of the motoneurones themselves could be responsible for the maintained firing. 3. In confirmation of this hypothesis it was found that short-lasting depolarizing current pulses through the recording microelectrode could trigger a self-sustained firing in the motoneurone provided that the bias current (i.e. the holding potential) was kept within certain limits. Hyperpolarizing current pulses terminated the firing. When the spike-generating mechanism was inactivated (by long-lasting excessive depolarization) similar depolarizing and hyperpolarizing current pulses could initiate and terminate plateau potentials in the motoneurones. By grading the depolarizing current pulses it was found that the plateau potentials were of all-or-none character, typically around 10 mV in amplitude. The two levels of excitability which can be triggered by short-lasting excitation and inhibition of the motoneurones is referred to as 'bistable' behaviour of the motoneurones. 4. After an acute spinal transection, in the unanaesthetized cat, the bistable behaviour of the motoneurones disappeared. However, it reappears following intravenous injection of the serotonin precursor 5-hydroxytryptophan (50-120 mg/kg). 5. Individual triceps surae motor units were recorded by selective EMG electrodes during tonic stretch reflexes in the decerebrate preparations. Based on an analysis of their firing pattern during lengthening and shortening (or vibration) of the muscle it is suggested that plateau potentials in motoneurones are recruited during the tonic stretch reflex. Furthermore, it is argued that a quantitatively important part of the depolarization of motoneurones during the tonic stretch reflex indeed originates from these plateau potentials.(ABSTRACT TRUNCATED AT 400 WORDS)

5-Hydroxytryptophan↗
PubMed1985

Intrinsic control of electroresponsive properties of transplanted mammalian brain neurons.

The present study presents the first analysis of neurons in mammalian brain transplants based on intracellular recording. The results, obtained in brain slices including both donor and host tissue, showed that neuronal precursor cells in embryonic transplants retained their ability to complete their normal differentiation of cell-type-specific electroresponsive properties. Distortions in cell aggregation and synaptic connectivity did not affect this aspect of neuronal differentiation.

Animals↗
PubMed1985

Ca++ dependent bistability induced by serotonin in spinal motoneurons.

The plateau potential, responsible for the bistable state of spinal motoneurons, recently described in the decerebrate cat, was suggested to depend on serotonin (Hounsgaard et al. 1984). In an in vitro preparation of the spinal cord of the turtle we now show that serotonin, applied directly to the bath, transforms the intrinsic response properties of motoneurons, uncovering a plateau potential and voltage sensitive bistability. The changes induced by serotonin were blocked by Mn++, while the plateau potential and the bistability remained after application of tetrodotoxin. We conclude that serotonin controls the expression of a Ca++ dependent plateau potential in motoneurons.

Animals↗
PubMed1984

Intrinsic membrane properties causing a bistable behaviour of alpha-motoneurones.

In decerebrate cats a train of impulses in Ia afferents may lead to a sustained increase in excitability of alpha-motoneurones of homonymous and heteronymous muscles. It was previously suggested that this long-lasting excitability increase reflects a maintained synaptic input to the motoneurones from excitatory interneurones. With intracellular recording from motoneurones we here demonstrate that the sustained increase of alpha-motoneurone activity is due to an all-or-none plateau depolarization. This plateau can be induced by a short train of excitatory synaptic potentials or a brief, intracellularly injected depolarizing current pulse and is terminated by a short train of inhibitory synaptic potentials or a hyperpolarizing current pulse. It is concluded that maintained motor unit firing triggered by a brief train of impulses in Ia afferent reflects an intrinsic bistable behaviour of alpha-motoneurones.

Animals↗
PubMed1983

Potassium accumulation around individual purkinje cells in cerebellar slices from the guinea-pig.

K+-selective micropipettes were used to measure external K+ concentration [( K+]o) in the immediate vicinity of Purkinje cells in slices from guinea-pig cerebellum. The cells were either spontaneously active or were polarized via a separate intracellular micro-electrode. The level of [K+]o rose by 1-3 mM around the soma and dendrites of Purkinje cells during spike activity. The increases in [K+]o were usually greater during Ca2+-mediated spikes than during Na+-mediated spikes. This was even true at the soma where the Ca2+ spike only invaded electrotonically from the dendrites, in contrast to the Na+ spikes which were generated at the soma. No [K+]o changes were seen in the vicinity of Purkinje cells when the cells were hyperpolarized with current passage nor was any [K+]o change seen during subthreshold depolarizations. In glial cells, however, a hyperpolarizing current reduced [K+]o while a depolarizing current increased [K+]o in a symmetrical manner. When Ba2+ was substituted for Ca2+ in the bathing Ringer solution, prolonged plateau-potential spikes could be evoked from Purkinje cells. These spikes were accompanied by large [K+]o elevations but the plateau potentials outlasted the [K+]o elevations. These experiments suggest that large [K+]o increases can occur in the absence of Ca2+-mediated K+ conductances. Substitution of Mn2+ for Ca2+ in the Ringer solution removed some of the [K+]o increases at the Purkinje cell soma. Addition of tetrodotoxin to normal Ringer solution also reduced, but did not abolish the [K+]o increases at the soma. These experiments confirmed that both Na+ and Ca2+ spikes were involved in the [K+]o change. The diffusion characteristics of the slices were determined by an ionophoretic method using tetramethylammonium and ion-selective micropipettes. The extracellular volume fraction of the slice averaged 0.28 while the tortuosity averaged 1.84. These values were close to those found previously in the intact rat cerebellum. These data were used to make quantitative estimates of the expected [K+]o accumulation in the vicinity of a single cell (see Appendix). Such estimates showed reasonable agreement with the measured values. Our data show that quite large increases in [K+]o may occur around single Purkinje cells. Such increases have previously only been evident during the activation of cell populations in mammalian preparations. The present results are probably due to the superior recording conditions of the slice. Implications for intercellular communication are discussed.

Action Potentials↗
PubMed1983

Diffusion in the slice microenvironment and implications for physiological studies.

The brain cell microenvironment includes the extracellular space surrounding the cell together with the cellular elements that define the space. The dense packing of cells in the mammalian nervous system ensures that the extracellular space is narrow but highly complex in geometry. Recent studies with ion-selective micropipettes have revealed that the cerebellar slice can support changes in [K+]o that resemble those seen in the intact preparation. In the slice, [K+]o responses of individual cells can even be resolved. Studies with iontophoretic techniques and quantitative analysis in the slice have shown that the extracellular space has diffusion properties, characterized by a volume fraction and a tortuosity, that are very similar to those seen in the intact animal. These data confirm that the microenvironment in the slice is comparable to that in the intact animal. The diffusion parameters can be used to make predictions about the time necessary for substances to diffuse into slices under various conditions. Such estimates, together with other studies, indicate that it is probably inadvisable to use slices with thicknesses in excess of 300--400 micrometers, and that the bathing conditions can be critical in maintaining slice viability.

Animals↗
PubMed1982

Anoxia increases potassium conductance in hippocampal nerve cells.

The effect of anoxia on nerve cell function was studied by intra- and extracellular microelectrode recordings from the CA1 and CA3 region in guinea pig hippocampal slices. Hyperpolarization and concomitant reduction of the nerve cell input resistance was observed early during anoxia. During this period the spontaneous activity first disappeared, then the evoked activity gradually disappeared. The hyperpolarization was followed by depolarization and an absence of a measurable input resistance. All the induced changes were reversed when the slice was reoxygenated. Reversal of the electro-chemical gradient for Cl- across the nerve cell membrane did not affect the course of events during anoxia. Aminopyridines blocked the anoxic hyperpolarization and attenuated the decrease of membrane resistance, but had no effect on the later depolarization. Blockers of synaptic transmission. Mn++, Mg++ and of Na+-channels (TTX) were without effect on the nerve cell changes during anoxia. It is suggested that the reduction of nerve cell excitability in anoxia is primarily due to increased K+-conductance. Thus, the nerve cells are hyperpolarized and the input resistance reduced, causing higher threshold and reduction of synaptic potentials. The mechanism of the K+-conductance activation is unknown at present.

Animals↗
PubMed1979

Dendritic spikes in Purkinje cells of the guinea pig cerebellum studied in vitro.

Extracellular spikes were recorded simultaneously from dendrites and somata of Purkinje cells in thin cerebellar sections. Spontaneously occurring dendritic spikes were biphasic with the initial phase positive. Triphasic dendritic spikes with a large negative phase appeared during electrophoretic application of glutamate. In media containing procaine, tetrodotoxin, or high concentrations of KCl, negative dendritic spikes occurred whereas soma spikes were abolished. The negative dendritic spikes were suppressed by CoCl2 or MnCl2. Electrical stimulation elicited climbing fibre responses in somata and large negative waves in dendrites. Spikes of dendritic origin were different from those reflecting electrotonic spread of soma spikes. The relation between soma spikes and active dendritic spikes is discussed.

Animals↗