Biomedical subjects

H L Haas

Publications and source records attributed to H L Haas.

At least 91 records · Page 5Linked to original sources

PubMed1990

An electrophysiological study of the ontogenesis of adenosine receptors in the CA1 area of rat hippocampus.

The depressant effect of adenosine (Ad) was studied electrophysiologically in hippocampal slices from 5-, 10-, 15-, 20-, 30- and 120-day-old rats. Ad (10 microM) depressed the field EPSP in CA1 to the same extent in all age groups. Caffeine (Caf), an Ad receptor antagonist, enhanced and nitrobenzylthioinosine (NBI), an Ad uptake blocker, depressed the field EPSP. Both these effects were, however, less prominent in slices from younger animals, a finding consistent with lower extracellular levels of endogenous Ad in neonatal rats.

Action Potentials↗

PubMed1990

Effects of histamine on dentate granule cells in vitro.

Hippocampal slices from rat brain were exposed to histamine and related substances in a perfusion chamber. Granule cells of the dentate gyrus were studied with conventional extra- and intracellular recording and a single electrode voltage clamp. Histamine caused, through activation of H(2)-receptors, a small depolarization, an increase in the number of synaptic and action potentials, a block of the long lasting (but not the early) component of spike afterhyperpolarizations and a reduction of the accommodation of action potential firing. These effects were mimicked by forskolin (suggests activation of adenylate cyclase). In voltage clamp, histamine blocked a long lasting calcium-dependent outward tail current without any reduction of inward current. Thus histamine selectively blocks the late calcium-dependent potassium current in dentate granule cells which receive histaminergic input from the posterior hypothalamus. Histamine also reduces the field excitatory postsynaptic potential evoked by perforant path stimulation. These actions allow for a powerful modulation of excitatory signals and an effective regulation of hippocampal excitability.

Action Potentials↗

PubMed1990

Two transient outward currents in histamine neurones of the rat hypothalamus in vitro.

1. The transient outward current exhibited by the histamine neurones of the tuberomammillary nucleus was studied using the single-electrode voltage clamp technique in an in vitro rat hypothalamic slice preparation. 2. The transient outward current exhibited steady-state inactivation at the resting potential. Inactivation was removed by priming hyperpolarization with a V1/2 of -85 +/- 1.2 mV, while the V1/2 for activation was -60.3 +/- 2.1 mV. 3. The decay of the transient outward current was best fitted by two exponentials with time constants of 104 +/- 36 and 568 +/- 128 ms. These two components were provisionally termed IA,f and IA,s for the fast and slowly decaying currents, respectively. 4. Removal of inactivation was time dependent; inactivation was fully removed by hyperpolarizing pulses to -110 mV of 200 ms or greater duration. Removal of inactivation of IA,f was rapid, becoming complete with hyperpolarizing pre-pulses of 50 ms or greater, while removal of inactivation of IA,s was not complete until hyperpolarizing pre-pulses were 200 ms in duration. 5. The fast decaying current IA,f was selectively blocked by 1 mM-4-aminopyridine. Tetraethylammonium chloride (10 mM) had no effect on either IA,f or IA,s. 6. The inactivation curves for IA,s, determined both by using the values obtained from the amplitude of the computed slower exponential function as well as that of the current remaining in 1 mM 4-aminopyridine, were negative to those of IA,f. Similarly derived activation curves for IA,s were positive to those of IA,f. 7. Superfusion with a nominal 0 Ca2+ medium containing 10 mM-Mg2+ did not reduce the maximal transient outward current. 8. The reversal potential of IA,s with 2.5 mM-K+ in the medium was -95 +/- 3 mV; the reversal potential of IA,f was at least 15 mV negative to that of IA,s. 9. It is concluded that histaminergic tuberomammillary neurones possess at least two transient outward currents which can be distinguished on the basis of their rates of decay, 4-aminopyridine sensitivity, voltage dependence and reversal potentials.

4-Aminopyridine↗

PubMed1989

Hippocampal mossy fiber distribution and long-term potentiation in two inbred mouse strains.

We studied long-term potentiation in the inbred mouse strains DBA/2 and C3H/He known to be different in both hippocampal mossy fiber distribution and several aspects of learning. Tetanic stimulation of mossy fibers resulted in a significantly stronger increase of the population spike amplitude in the CA3 pyramidal cell layer of C3H mice. This result suggests that the extent of the CA3 hippocampal mossy fiber projection correlates with synaptic efficacy in mice.

Action Potentials↗

PubMed1989

Cholinergic activation of medial pontine reticular formation neurons in vitro.

In vivo microinjections of cholinergic compounds into the medial pontine reticular formation have produced some or depending on the injection site, all of the phenomena of REM, thus providing the only adequate pharmacological model of this behavioral state. The necessary anatomical substrate, a cholinergic projection to the mPRF was recently demonstrated, however the direct effect of cholinergic agonists on mPRF neurons is unknown. We have examined the effects of carbachol on mPRF neurons recorded in vitro from brainstem slices of Sprague-Dawley rats (8-10 days old). Three kinds of response to the application of carbachol (0.5-1 microM) were observed (n = 15) as follows: a depolarizing response (67%), a hyperpolarizing response (20%) and a biphasic response consisting of a hyperpolarizing response followed by a depolarizing response (13%). Under voltage clamp control, the depolarizing response was observed as an inward current resulting from a decrease in conductance which was constant over the membrane potential range of -100 to -50 mV. Reversal potential was negative to -80 mV. An increase in the excitability of neurons (as measured by responses to identical intracellularly applied depolarizing current pulses) during the depolarizing responses was due to the increase in steady state inward current. When intracellular DC current of equal amplitude but opposite polarity was applied, no increase in excitability was observed. This response was always blocked by the addition of atropine (0.5-1 microM) to the perfusate. The hyperpolarizing response was observed as an increase in outward current due to an increase in conductance with marked voltage sensitivity (over the range of -100 to -50 mV) characteristic of the anomalous rectifier. Preliminary data indicated that the hyperpolarizing response was more sensitive to pirenzepine (complete blockade at 1.0 microM) than the depolarizing response (complete blockade at 2 microM) but neither response was affected by pirenzepine concentrations of 200 nM or less. Cholinergic effects on evoked depolarizing PSPs were examined on neurons with depolarizing (n = 3) and biphasic (n = 1) responses and in all cases, the PSPs were enhanced. This enhancement was blocked by atropine. In conclusion, it is suggested that activation of two different muscarinic receptors (neither of which is the M1 receptor) on mPRF neurons results in two different responses, a decrease in a voltage-insensitive potassium conductance and an increase in the anomalous rectifier.

Acetylcholine↗

PubMed1989

Action of anticonvulsants on hippocampal slices in Mg-free medium.

The effects of six prototype anticonvulsant drugs were investigated on epileptiform field potential discharges evoked in hippocampal slices of rats by removing magnesium ions from the perfusion fluid in order to reveal a possible interaction with N-methyl-D-aspartate (NMDA) receptor activation. All drugs reduced the multiple discharges with the following order of potency: midazolam greater than carbamazepine = phenytoin = phenobarbital greater than ethosuximide = valproate. They had a stronger depressant effect on the later population spikes but none of them abolished the epileptiform discharge. These effects can be explained by known mechanisms of action of the anticonvulsants tested and lend no support for a specific interaction with NMDA receptors.

Animals↗

PubMed1989

The brain histamine system in vitro.

The electrophysiological properties of identified tuberomammillary histamine neurones were investigated in explant and slice preparations. The effects of histamine were studied on target neurones, mainly in the hippocampal slice. The results describe an important modulatory role of this diffusely projecting system.

Action Potentials↗

PubMed1989

Characterization of inhibition mediated by adenosine in the hippocampus of the rat in vitro.

1. Intracellular recordings with single-electrode voltage clamp were employed to study the mechanism of adenosine-elicited inhibition of CA1 neurones of the rat in vitro. 2. Adenosine elicits a steady-state outward current in association with an increase in conductance. The driving force varied with external potassium concentration as predicted by the Nernst equation for a change primarily in potassium permeability. 3. Adenosine current was blocked by high concentrations of 4-aminopyridine or barium. In the majority of neurones this current was voltage insensitive. In the remainder, the current was inwardly rectifying. The rectification was blocked by tetraethylammonium. 4. When the adenosine-elicited potassium current was blocked, slow inward currents, normally carried by calcium, were unaffected by adenosine. We conclude that this adenosine inhibition is mediated by an increase in a voltage- and calcium-insensitive potassium conductance in CA1 neurones.

4-Aminopyridine↗

PubMed1988

Effects of purinoceptor agonists on electrophysiological properties of rat mesencephalic trigeminal neurones in vitro.

Intracellular recordings were performed in a midpontine slice preparation of the rat brain containing the mesencephalic trigeminal nucleus (MTN). In spite of the previous demonstration of an adenosine deaminase-containing plexus terminating on this nucleus, adenosine, adenosine 5'-triphosphate (ATP), alpha,beta-methylene ATP (alpha,beta-meATP) and 2-methylthio ATP all failed to influence the membrane potential or input resistance of the MTN cells. Moreover, there was no apparent change in the shape of action potentials in the presence of these drugs, and the accomodation of the firing rate to depolarizing pulses was not affected either.

Action Potentials↗

PubMed1988

Organotypic culture of central histamine neurons.

Organotypic cultures of histaminergic tuberomammillary (TM) neurons were grown using explants obtained from newborn rats. The cultures were examined after immunohistochemical localization of the histamine synthetic enzyme, L-histidine decarboxylase (HDC). The morphological properties of the somata, dendrites and axons of HDC-immunoreactive TM neurons in organotypic culture were virtually indistinguishable from those seen in situ. Extensive plexuses of HDC-immunopositive axons, including growth cones, were seen within the hypothalamus, the plasma surrounding the explant and co-cultured hippocampus. Organotypic cultures of TM histamine neurons, and co-cultures with their targets, provide a useful model system for studying several aspects of central histaminergic neurobiology.

Animals↗

PubMed1988

Endogenous adenosine inhibits hippocampal CA1 neurones: further evidence from extra- and intracellular recording.

Extracellular and intracellular recordings from CA1 pyramidal neurones of rats in vitro were used to study the effects of endogenous and exogenously applied adenosine. The adenosine receptor antagonist, caffeine, enhanced the intracellular recorded e.p.s.p.-i.p.s.p. sequence evoked by stimulation of the stratum radiatum which is antagonized by exogenous adenosine. The late, potassium dependent i.p.s.p. was not antagonized. The adenosine uptake inhibitor, nitrobenzylthioinosine (NBTI), mimicked the effects of exogenously applied adenosine. The effects of NBTI and of exogenously applied adenosine were antagonized by caffeine in the same manner. Exposure to adenosine deaminase enhanced the evoked field e.p.s.p. During this enhancement caffeines effects were significantly reduced. In low calcium high magnesium medium which abolishes synaptic activity, adenosine deaminase increased, NBTI decreased cell firing. We conclude that endogenous adenosine, release by a calcium independent mechanism, can exert an inhibitory tone on CA1 neurones in vitro. This is consistent with a role for adenosine as a mediator of negative feedback between the metabolic state and electrophysiological activity of nervous tissue.

Adenosine↗

PubMed1988

Membrane properties, response to amines and to tetanic stimulation of hippocampal neurons in the genetically epileptic mutant mouse tottering.

The petit-mal seizures of the "tottering" mutant mouse (tg) have been attributed to an exaggerated noradrenergic projection from locus coeruleus to the telencephalon (Noebels 1984). In order to investigate the possible epileptogenic mechanisms involved, we have compared hippocampal slices from epileptic (tg/tg) and phenotypically healthy (tg/+) mice. Resting potentials, action potentials and afterpotentials, membrane impedances and time constants were not significantly different in 11 neurons from each group. Bath application of noradrenaline, isoproterenol and histamine or a transient exposure to Mg++-free medium caused a long lasting increase in extracellularly recorded population spikes induced in CA1 by electrical stimulation of stratum radiatum. Isoproterenol blocked the calcium dependent afterhyperpolarization and accommodation of firing. Tetanization of afferent fibres evoked post-tetanic potentiation and long-term potentiation. All these results are qualitatively similar to those previously described in rats and guinea pigs and have revealed no significant difference between tg/tg and tg/+ mice.

Action Potentials↗

PubMed1988

Membrane properties of histaminergic tuberomammillary neurones of the rat hypothalamus in vitro.

1. Intracellular recordings were obtained from neurones of the tuberomammillary nucleus in an in vitro explant of the rat hypothalamus. 2. Tuberomammillary neurones were spontaneously active (2.1 +/- 0.6 Hz) at the resting potential which was around -50 mV. Action potential amplitude was 75 +/- 8 mV (n = 9); mean mid-amplitude duration was 1.8 +/- 0.4 ms (n = 9). 3. The mean input resistance of tuberomammillary neurones was 176 +/- 42 M omega (n = 30), and the mean membrane time constant was 19.8 +/- 5.3 ms (n = 30). These neurones exhibited inward rectification with hyperpolarization from the resting potential, and transient outward rectification at the offset of hyperpolarizing electrotonic pulses. 4. Action potentials were followed by an after-hyperpolarization of 300-600 ms duration and 12-18 mV amplitude. This after-hyperpolarization had a reversal potential around -80 mV, was abolished by intracellular loading with caesium, and was reduced but not abolished by bath application of either cadmium, cobalt or nickel. 5. Tetrodotoxin abolished spontaneous action potentials. Further addition of tetraethylammonium ions revealed a regenerative spike which was reversibly blocked by the addition of cobalt. 6. That tuberomammillary neurones exhibiting these properties were indeed histaminergic was confirmed in five cases by intracellular ionophoresis of Lucifer Yellow and subsequent double labelling by immunofluorescent localization of the histamine synthetic enzyme L-histidine decarboxylase.

Action Potentials↗

PubMed1987

Long-term potentiation induced by physiologically relevant stimulus patterns.

Single pulse stimuli were delivered to the Schaffer collaterals in the in vitro hippocampal slice preparation. Local application of bicuculline to the CA3 region resulted in a series of population cell bursts in CA3, resembling the neuronal patterns which occur in the normal, freely moving rat during hippocampal sharp waves. These bicuculline-induced cell bursts in CA3 resulted in long-term potentiation (LTP) of the CA1 response. These findings suggest that the naturally occurring hippocampal sharp waves may reflect events analogous to artificially induced LTP.

Animals↗

PubMed1987

Noradrenaline blocks potassium conductance in rat dentate granule cells in vitro.

The actions of noradrenaline and the beta-adrenergic agonist, isoproterenol, were studied on the dentate gyrus in hippocampal slices from rats using extra- and intracellular recording. These agents facilitated field EPSPs (excitatory postsynaptic potentials) and population spikes evoked by perforant path stimulation. Intracellular recording revealed an attenuation of the long lasting afterhyperpolarization (AHP) and the accommodation of cell discharge in response to depolarizing current injection. It is suggested that beta-receptor activation blocks a calcium-dependent potassium current.

Animals↗

PubMed1987

Action and location of neuropeptide tyrosine (Y) on hippocampal neurons of the rat in slice preparations.

The action of bath applied NPY (1-1,000 nM) was investigated on hippocampal slices of the rat with extra- and intracellular recording. Neuropeptide Y (NPY) at 10-1,000 nM caused a concentration-dependent, long-lasting reduction of excitatory postsynaptic potentials (EPSPs) in the hippocampal subfield CA1 and the area dentata, and an even stronger reduction of population spikes. Paired pulse experiments with low intensity, stimulation-evoked PSPs showed a marked increase in facilitation in the presence of NPY, indicating a presynaptic action. Spontaneous burst firing of CA1 pyramidal cells in low calcium, high magnesium medium was reduced, indicating a partially postsynaptic inhibitory action of NPY on their dendrites. Intracellular recording from CA1 somata during NPY administration revealed a reduction of the amplitudes of excitatory-inhibitory postsynaptic potential (EPSP-IPSP) sequences in the absence of changes in membrane potential and conductance. Accommodation of firing during long depolarizing pulses and afterhyperpolarizations were unchanged. The innervation pattern of NPY immunoreactive fibers in the same regions was studied in slices adjacent to the ones used for electrophysiology by using antisera against NPY and light and electron microscopy. There is a dense innervation of CA1 by NPY-immunoreactive axons and terminals, particularly in the stratum moleculare. NPY-immunoreactive neurons are present in the stratum oriens and pyramidale. The NPY labeled axons of the stratum moleculare participate in numerous synaptic contacts with the smaller dendritic elements in this layer, many of which belong to pyramidal neurons. These observations provide evidence for a dendritic NPY-immunoreactive innervation of CA1 neurons, which is in keeping with the electrophysiological effects of NPY on pyramidal neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Comparative investigations on the actions of ACTH1-24, somatostatin, neurotensin, substance P and vasopressin on locus coeruleus neuronal activity in vitro.

A considerable number of neuropeptides have been localized immunohistochemically in the area of the locus coeruleus of the rat. The objective of this study was to assess the actions of some of these transmitter candidates on spontaneously active locus coeruleus neurons in vitro. The effects of bath-applied peptides on the discharge rate of individual locus coeruleus neurons were investigated. A midpontine slice preparation of the gerbil brain was used. Excitatory dose-dependent effects were found with four peptides with the following rank order of potency: Substance P, (Arg8)-vasopressin, neurotensin, ACTH1-24. Somatostatin hyperpolarized all neurons tested. Given the pronounced effects seen with substance P, somatostatin and vasopressin in the nanomolar range, it is conceivable that these peptides may have a role in regulating neuronal activity in locus coeruleus.

Animals↗

PubMed1986

A low threshold calcium spike mediates firing pattern alterations in pontine reticular neurons.

Intracellular electrical recordings in an in vitro slice preparation of the brainstem medial pontine reticular formation, a region thought to be important in mediation of desynchronized sleep phenomena, demonstrate a population of neurons that have a calcium-dependent, low threshold spike. This low threshold spike was inactivated at relatively depolarized membrane potential levels and, when this spike was deinactivated, it induced a burst of action potentials. The membrane potential dependence of the spike may underlie changes in action potential firing patterns associated with behavioral state change because the baseline membrane potential in neurons of the medial pontine reticular population depolarizes during passage from waking and slow wave sleep to desynchronized sleep, which is characterized by the absence of burst firing.

Action Potentials↗