Search PubMed⌕ Search

Biomedical subjects

D Schmitz

Publications and source records attributed to D Schmitz.

At least 55 records · Page 3Linked to original sources
PubMed1998

Serotonin reduces polysynaptic inhibition via 5-HT1A receptors in the superficial entorhinal cortex.

The superficial cells of the entorhinal cortex (EC), main input to the hippocampus, receive a serotonergic input from the raphe nuclei and express 5-hydroxytryptamine creatine sulfate complex (5-HT) receptors at high density. With the use of intracellular recordings, we investigated the effects of serotonin on synaptic inhibition of layer II and III neurons of the EC. Serotonin reduced both polysynaptic fast and slow inhibitory postsynaptic potentials (IPSPs) in projection neurons of the superficial EC. Polysynaptic fast and slow IPSPs were depressed by serotonin in a dose-dependent manner (0.1-100 microM). Serotonin in a concentration of 1 microM reduced the amplitudes of polysynaptic fast and slow IPSPs by approximately 40 and 50%, respectively. To identify the subtype of the 5-HT-receptor mediating the effects on polysynaptic IPSPs, we applied various 5-HT-receptor agonists and antagonists. Although the serotonin agonists for the 5-HT1B,2C,3 receptors were ineffective, the effects were mimicked by the 5-HT1A-receptor agonists (8-OH-DPAT, 5-CT) and prevented by the 5-HT1A-receptor antagonist NAN-190. To look at the direct effects of 5-HT on inhibitory interneurons, we elicited monosynaptic IPSPs in the absence of excitatory synaptic transmission. In contrast to the polysynaptic IPSPs, monosynaptic IPSPs were not significantly affected by serotonin. Recordings from putative inhibitory interneurons revealed that their excitatory postsynaptic potentials (EPSPs) were reversibly reduced by serotonin. We conclude that serotonin suppresses polysynaptic inhibition in projection neurons of layers II and III of the EC by depression of EPSPs on inhibitory interneurons via 5-HT1A receptors.

2-Amino-5-phosphonovalerate↗
PubMed1997

Effects of serotonin on synaptic and intrinsic properties of rat subicular neurons in vitro.

Intracellular recordings were performed to study the effects of 5-HT on membrane properties and EPSP/IPSP responses of subicular neurons in rat combined hippocampal-entorhinal cortex slices. Application of 5-HT induced in 76% of the investigated subicular cells a hyperpolarization and a reduction of membrane resistance. In bursting neurons, 5-HT caused a reduction of the depolarizing envelope underlying burst discharges and attenuated the subsequent afterhyperpolarization. While 5-HT decreased isolated AMPA/kainate and NMDA receptor-mediated responses as well as slow IPSPs, we could not find a consistent effect on isolated fast IPSPs. Since in approximately 25% of subicular neurons EPSPs and slow IPSPs were reduced without any increase of membrane conductance, we conclude that 5-HT has in addition to membrane effects also effects on synaptic currents.

Animals↗
PubMed1997

The activation domain of the maize transcription factor Opaque-2 resides in a single acidic region.

The maize (Zea mays L.) endosperm specific transcription factor, encoded by the Opaque-2(O2) locus, functions in vivo to activate transcription from its target promoters.O2 regulates the expression of a major storage protein class, the 22 kDa zeins, and of a type I ribosome inactivating protein, b-32, during maturation phase endosperm development. The coding sequence of O2, which indicates it to be a member of the basic region-leucine zipper (bZIP) class of DNA-binding proteins, contains a number of regions rich in either proline or acidic residues which are candidates for activation domains. In functional assays using tobacco mesophyll protoplasts, the level of transactivation conferred by a series of O2-deletion constructs was tested using as a reporter a fusion of the b-32 target promoter to beta-glucuronidase (GUS). The results indicate that O2 has a single acidic activation domain, located near the N-terminus of the protein (amino acids 41-91). The ability of a shorter part of this domain (amino acids 39-82) to confer transactivation was also demonstrated in domain swapping experiments, using fusions of the O2 polypeptide sequence to the DNA-binding domain of the parsley (Petroselinum crispum) transcription factor CPRF1.

DNA-Binding Proteins↗
PubMed1997

Systemic administration of the phencyclidine compound MK-801 affects stimulus-induced field potentials selectively in layer III of rat medial entorhinal cortex.

Phencyclidine and related compounds such as MK-801 produce psychotic symptoms, which closely resemble schizophrenia. MK-801 causes lesions in different corticolimbic regions including the medial entorhinal cortex (mEC). Using electrophysiological recordings in brain slices we tested whether several hours of systemic administration of MK-801 affect stimulus-induced field potentials (FPs) in the mEC. Stimulus-induced FPs were selectively reduced in layer III, but not in layers II and V of the mEC. In contrast, MK-801 applied acutely over the bath in low concentration had no significant effect on evoked FPs. Since the principal cells of layer III project directly to area CA1 and the subiculum, the selective effects of MK-801 may have implications for the transfer of information to the hippocampus.

Animals↗
PubMed1997

Serotonin blocks different patterns of low Mg2+-induced epileptiform activity in rat entorhinal cortex, but not hippocampus.

Low Mg2+-induced epileptiform activity in the entorhinal cortex is characterized by an initial expression of seizure-like events followed by late recurrent discharges. Both these forms of activity as well as the transition between them were blocked by serotonin. In contrast, serotonin had little effect upon the epileptiform activity in areas CA3 and CA1 of the hippocampus. Both forms of epileptiform activity in the entorhinal cortex are sensitive to N-methyl-D-aspartate receptor antagonists and it is shown here that serotonin blocked both types of epileptiform activity through an effective concentration-dependent reduction of N-methyl-D-aspartate receptor-mediated excitatory postsynaptic potentials in deep layer entorhinal cortex cells. Serotonin also prolonged or even prevented the transition between the two types of epileptiform activity and we suggest that this may be through activation of the Na+/K+-ATPase. The resistance of epileptiform activity in CA1 and CA3 to serotonin was most likely related to the inability of serotonin to reduce Schaffer collateral-evoked excitatory postsynaptic potentials. Given the strong serotonergic inputs to both the hippocampus and entorhinal cortex, the differential sensitivity of the two regions to serotonin suggests functional differences. In addition since the late recurrent discharges in the entorhinal cortex are resistant to all clinically used anticonvulsants, serotonin may open new avenues for the development of novel anticonvulsant compounds.

Animals↗
PubMed1997

Effects of glutamate receptor agonists and antagonists on Ca2+ uptake in rat hippocampal slices lesioned by glucose deprivation or by kainate.

The functional relevance of presynaptic glutamate receptors in controlling presynaptic Ca2+ influx and thereby transmitter release is unknown. To test if presynaptic Ca2+ entry in the hippocampus is controlled by glutamate autoreceptors, we created a hippocampal slice preparation for investigation of presynaptic Ca2+ signals with Ca(2+)-sensitive microelectrodes after lesioning of neurons by glucose deprivation or kainate. Stratum radiatum and alveus stimulation-induced postsynaptic field potential components were irreversibly abolished in areas CA1 and CA3 of lesioned slices, whereas stratum radiatum stimulation still evoked afferent volleys. Repetitive stimulation of the stratum radiatum still induced decreases in extracellular Ca2+ concentration. Repetitive stimulation of the alveus no longer induced decreases in extracellular Ca2+ concentration, suggesting complete damage of pyramidal cells. The stratum radiatum stimulation-induced decreases in extracellular Ca2+ concentration in lesioned slices were comparable to those elicited during application of the glutamate antagonists 6-cyano-7-nitroquinoxaline-2,3-dione and L-2-amino-5-phosphonovalerate. In lesioned slices the stimulus-induced presynaptic Ca2+ influx was reversibly reduced by kainate. RS-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), N-methyl-D-aspartate and glutamate without effects on afferent volleys. The kainate and N-methyl-D-aspartate effects on presynaptic Ca2+ signals were partly sensitive to 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(f)quinoxaline and L-2-amino-5-phosphonovalerate, respectively, while the AMPA effects were not significantly affected by 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(f)quinoxaline, suggesting involvement of a novel glutamate receptor subtype. The involvement of a novel glutamate receptor subtype was supported by our findings that ionotropic glutamate receptor agonists also reduce presynaptic Ca2+ influx under conditions of blocked synaptic transmission by 6-cyano-7-nitroquinoxaline-2,3-dione and L-2-amino-5-phosphonovalerate. 1-Aminocyclopentane-trans-1,3-dicarboxylic acid had no significant effect on presynaptic Ca2+ entry. Also, the presynaptic Ca2+ influx was not influenced by the glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione, 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(f)quinoxaline and L-2-amino-5-phosphonovalerate when applied alone. Low kainate concentrations (5 microM) reduced presynaptic Ca2+ signals in area CA3 but not in area CA1, demonstrating the higher affinity of presynaptic kainate receptors on mossy fibre terminals.

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

Morphological and electrophysiological characterization of layer III cells of the medial entorhinal cortex of the rat.

Entorhinal cortex layer III cells send their axons into hippocampal area CA1, forming the less well studied branch of the perforant path. Using electrophysiological and morphological techniques within a slice preparation, we can classify medial entorhinal cortex layer III cells into four different types. Type 1 and 2 cells were projection cells. Type 1 cells fired regularly and possessed high input resistances and long membrane time constants. Electrical stimulation of the lateral entorhinal cortex revealed a strong excitation by both N-methyl-D-aspartate and non-N-methyl-D-aspartate receptor-mediated excitatory postsynaptic potentials. Type 2 cells accommodated strongly, had lower input resistances, faster time constants and featured prominent synaptic inhibition. Type 1 and 2 cells responded to repetitive synaptic stimulation with a prolonged hyperpolarization. We identified the two other, presumed local circuit, cell types whose axons remained within the entorhinal cortex. Type 3 cells were regular firing, had high input resistances and slow membrane time constants, while type 4 cells fired at higher frequencies and possessed a faster time constant and lower input resistance than type 3 neurons. Type 3 cells presented long-lasting excitatory synaptic potentials. Type 4 neurons were the only ones with different responses to stimulation from different sites. Upon lateral entorhinal cortex stimulation they responded with an excitatory postsynaptic potential, while a monosynaptic inhibitory postsynaptic potential was evoked from deep layer stimulation. In contrast to type 1 and 2 neurons, none of the local circuit cells could be antidromically activated from deep layers, and prolonged hyperpolarizations following synaptic repetitive stimulation were also absent in these cells. Together, the complementing morphology and the electrophysiological characteristics of all the cells can provide the controlled flexibility required during the transfer of cortical information to the hippocampus.

2-Amino-5-phosphonovalerate↗
PubMed1997

Prolonged inhibitory potentials in layer III projection cells of the rat medial entorhinal cortex induced by synaptic stimulation in vitro.

The entorhinal cortex projects via layer III neurons directly to the hippocampal area CA1 and the subiculum. We studied the functional properties of the medial entorhinal cortex projection cells in horizontal hippocampal-entorhinal cortex combined slices. These cells displayed, upon single-shock synaptic stimulation, an excitatory postsynaptic potential followed by a fast and/or slow inhibitory postsynaptic potential. Short train repetitive stimulation subthreshold for generation of action potentials induced a slow hyperpolarization of up to 20 s. Pharmacological analysis shows that the slow hyperpolarization could be divided into three components: i) the first component, which lasted 1 s, was sensitive to GABA(B) receptor antagonists; ii) the second component lasting for about 6 s was sensitive to atropine, suggesting muscarinic acetylcholinergic nature of these responses; iii) a late component lasting for up to 20 s was sensitive to naloxone, suggesting a role for opioids in its generation. The finding that layer III projection neurons to the hippocampus proper develop long-lasting hyperpolarizations suggests possible control mechanisms for the output functions of the entorhinal cortex.

Animals↗
PubMed1997

Frequency-dependent information flow from the entorhinal cortex to the hippocampus.

Storage and retrieval of information in the hippocampus is dependent on information transfer from the entorhinal cortex (EC). We studied how the separate pathways from layer II and III of the EC to the hippocampus are selected for information transfer during repetitive synaptic stimulation. Intracellular recordings were made from EC layer II and III projection cells in horizontal combined EC-hippocampal slices. Synaptic responses to stimulation of deep layers or the lateral EC with stimulus intensities approximately 70% of that required to elicit an action potential were analyzed during short trains of repetitive stimulation. The threshold intensities for induction of action potentials were in layer II cells 8.2 +/- 3.8 (SE) V, significantly larger than 4.4 +/- 1.5 V in type 1, and 5.2 +/- 3.3 V in type 2 layer III cells, respectively. During repetitive subthreshold stimulation with frequencies below 5 Hz the pathway from the EC layer II remained quiet and was preferentially activated with stimulation frequencies above 5 Hz. In contrast the EC layer III cells responded preferentially to low stimulus frequencies (<10 Hz) and became strongly inhibited when synaptically stimulated with frequencies above 10 Hz. Interestingly during stimulus frequencies between 5 and 10 Hz the likelihood that both layer II and III cells fire was large. Thus a frequency switch operates in the entrohinal cortex regulating output of layer II and III cells to the hippocampus. We suggest that such frequency dependent regulation of information flow presents a new principle of neuronal information processing.

Action Potentials↗
PubMed1996

Electrophysiological properties of rat subicular neurons in vitro.

The electrophysiological properties of 46 bursting cells and 39 regular firing cells were studied in the subiculum of rat combined hippocampal-entorhinal cortex slices. In bursting cells we found a significantly higher resting membrane potential than in regular firing cells. Upon hyperpolarization both cell types expressed a delayed inward rectification with a subsequent afterdepolarization. While in regular firing cells longer lasting depolarizing current injection caused a train of action potentials with a rather marked decline of discharge frequency, bursting cells displayed only little frequency accommodation. Regular firing cells usually displayed a fast and a slow afterhyperpolarization following a train of action potentials, while bursting neurons present only a slow afterhyperpolarization.

Animals↗
PubMed1996

[A combination of normal physiologic management of delivery and epidural analgesia].

From the anaesthesiological aspect the authors recommend the method of loss of resistance during verification of the epidural space as a safer method (lower percentage of perforations of the spinal dura mater). At the mentioned concentrations and dosage the authors did not observe any motor disorders of the lower extremities. The assembled experience with a combination of physiological delivery with emphasis on the second stage of labour and epidural analgesia justify not only the statement that this combination is possible but that it is favourable for mother and foetus. The combination reduces considerably the disadvantages of both types of management of labour, it used isolated. It puts, however, much greater demands on the staff and the costs are higher. These disadvantages should, however, not influence humanitarian trends in obstetrics.

Adult↗
PubMed1995

Serotonin and 8-OH-DPAT reduce excitatory transmission in rat hippocampal area CA1 via reduction in presumed presynaptic Ca2+ entry.

The effect of 5-HT and its 1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on excitatory transmission in CA1 pyramidal cells was studied. Using concentrations of 5-HT within a range of 10-50 microM we observed no change in excitatory postsynaptic potentials (EPSPs) in CA1 cells evoked by Schaffer collateral stimulation. However, at higher concentrations, > or = 100 microM, 5-HT caused a significant decrease (30-40%) in EPSP/Cs, an effect that was also mimicked by 50 microM 8-OH-DPAT. A presumed presynaptic Ca2+ entry was measured in stratum radiatum following repetitive stimulation of the Schaffer collaterals with all excitatory synaptic transmission blocked. Both 5-HT and 8-OH-DPAT reduced this Ca2+ entry. These results suggest that 5-HT acts at presynaptic 5-HT1A receptors to reduce Ca2+ entry and thereby glutamatergic synaptic transmission.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

Effects of losigamone on synaptic potentials and spike frequency habituation in rat entorhinal cortex and hippocampal CA1 neurones.

Losigamone is an anticonvulsant both in vivo and in vitro. We here studied possible mechanisms for such effects with conventional intracellular recordings from pyramidal cells of area CA1 and entorhinal cortex in combined hippocampal-entorhinal cortex slices. Losigamone reversibly reduced the number of action potentials elicited by 1 s long depolarising current injections. In addition, the drug moderately reduced EPSP amplitudes while monosynaptic fast and slow IPSPs were unaffected.

Action Potentials↗
PubMed1995

Electrophysiology and morphology of a new type of cell within layer II of the rat lateral entorhinal cortex in vitro.

Using a combination of intracellular recording and morphological techniques, we describe the properties of a new cell type within layer II of the lateral entorhinal cortex. A thick and bifurcating apical dendrite and thinner basal dendrites extended from the pyramidal shaped cell body. The axon ramified within all superficial layers of the lateral entorhinal cortex. These pyramidal-like cells exhibited 2 pronounced electrophysiological features; a high threshold for spike generation, and their prominent excitatory synaptic potentials with little inhibition following lateral entorhinal cortex stimulation. The electrophysiological properties and the axonal morphology suggest that this cell type has a local information processing role within the lateral entorhinal cortex.

2-Amino-5-phosphonovalerate↗
PubMed1995

Serotonin reduces synaptic excitation of principal cells in the superficial layers of rat hippocampal-entorhinal cortex combined slices.

The cells of the entorhinal cortex receive a dense innervation of serotonergic fibres from the Raphe nuclei and express a high density of 5-hydroxytryptamine 1A (5-HT1A) receptors. We investigated the effects of serotonin on excitatory synaptic transmission in principal cells from entorhinal cortex layers II and III within hippocampal-entorhinal cortex combined slices. Although serotonin had an effect upon the membrane conductance of some, but not all cells, its most pronounced action was to reduce stimulus evoked excitatory synaptic potentials and currents (EPSP/Cs). Both alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and N-methyl-D-aspartate receptor-mediated EPSPs were reduced to similar extents over a range of concentrations. Since the principal cells in layer II and layer III are the main projection cells of the entorhinal cortex, these inhibitory effects of serotonin may have implications for the transfer of information to the hippocampus.

Action Potentials↗