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O Paulsen

Publications and source records attributed to O Paulsen.

At least 19 recordsLinked to original sources
PubMed2004

Distinct properties of carbachol- and DHPG-induced network oscillations in hippocampal slices.

The aim of this study was to compare and contrast the properties of gamma oscillations induced by activation of muscarinic acetylcholine or metabotropic glutamate receptors in the CA3 region of rat hippocampal slices. Both carbachol and the group I metabotropic glutamate receptor agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG), induced network oscillations in the gamma-frequency range (30-100 Hz). The M1 muscarinic receptor antagonist, pirenzepine, blocked carbachol-, but enhanced DHPG-induced oscillations, whereas LY 341495, an antagonist at metabotropic glutamate receptors, abolished DHPG-, but left carbachol-induced oscillations unchanged. There were significant differences in the peak frequency, maximal power, and spectral width of the two oscillations. Pharmacological experiments showed that both types of oscillation depend on fast excitatory and inhibitory synaptic transmission. Interestingly, activation of neurokinin-1 receptors by substance P fragment or enhancement of inhibitory synaptic currents by the benzodiazepine ligand, zolpidem, boosted DHPG-, but reduced the power of carbachol-induced oscillations. These results suggest that, although carbachol and DHPG might activate similar conductances in individual pyramidal cells, the oscillations they induce in slices involve different network mechanisms, most likely by recruiting distinct types of GABAergic interneuron.

Action Potentials↗
PubMed2002

Expression and distribution of metabotropic GABA receptor subtypes GABABR1 and GABABR2 during rat neocortical development.

To understand the possible contribution of metabotropic gamma-aminobutyric acid receptors (GABABR) in cortical development, we investigated the expression pattern and the cellular and subcellular localization of the GABABR1 and GABABR2 subtypes in the rat neocortex from embryonic day 14 (E14) to adulthood. At the light microscopic level, both GABABR1 and GABABR2 were detected as early as E14. During prenatal development, both subtypes were expressed highly in the cortical plate. Using double immunofluorescence, GABABR1 colocalized with GABABR2 in neurons of the marginal zone and subplate, indicating that these proteins are coexpressed and could be forming functional GABABRs during prenatal development in vivo. In contrast, only GABABR1 but not GABABR2 was detected in the tangentially migratory cells in the lower intermediate zone. During postnatal development, immunoreactivity for GABABR1 and GABABR2 was distributed mainly in pyramidal cells. Discrete GABABR1-immunopositive cell bodies of interneurons were present throughout the neocortex. In addition, GABABR1 but not GABABR2 was found in identified Cajal-Retzius cells in layer I. At the electron microscopic level, immunoreactivity for GABABR1 and GABABR2 was found in dendritic spines and dendritic shafts at extrasynaptic and perisynaptic sites throughout postnatal development. We further demonstrated the presynaptic localization of GABABR1 and GABABR2, as well as the association of the receptors with asymmetrical synaptic junctions. These results indicate potentially important roles for the GABABRs in the regulation of migratory processes during corticogenesis and in the modulation of synaptic transmission during early development of cortical circuitry.

Animals↗
PubMed2001

New excitement in cognitive space: between place cells and spatial memory.

Hippocampal principal neurons-'place cells'-exhibit location-specific firing. Recent work addresses the link between place cell activity and hippocampal memory function. New tasks that challenge spatial memory allow recording from single neurons, as well as ensembles of neurons, during memory computations, and insights into the cellular mechanisms of spatial memory are beginning to emerge.

Animals↗
PubMed2001

Short-term effects of four antibiotics on DNA synthesis in endothelial cells.

The irritating effect of parenterally administered antibiotics on vessels is a common clinical problem. In a previous study we found that solutions of three commonly used antibiotics, cefuroxime, erythromycin and dicloxacillin, exerted cytotoxic effects on endothelial cells after 24 hr exposure. In contrast benzylpenicillin did not have such effects. In the present study, endothelial cells of different origin were exposed to these four antibiotics at higher concentrations than in the previous investigation but only for 5, 30 and 60 min. Incorporation of 3H-thymidine in the cells as a measurement of DNA synthesis was used as cytotoxic assay. A concentration-dependent and time-related inhibition was found after exposure to erythromycin and dicloxacillin but not after exposure to cefuroxime and benzylpenicillin. The effects were similar on the three different cell types used in the experiments. This study demonstrates that the cytotoxic effects differ even after short-term exposure to the antibiotics. In contrast to the previous study, cefuroxime lacks cytotoxicity when endothelial cells are exposed for less than one hour. The short-term exposition model used in this study should be more predictive as it mimics in vivo conditions better.

Animals↗
PubMed2001

Fewer bacterial relapses after oral treatment with norfloxacin than with ceftibuten in acute pyelonephritis initially treated with intravenous cefuroxime.

This double-blind, multicentre study was performed at nine centres on a total of 171 patients who presented with fever (> 38.5 degrees C) and signs of acute pyelonephritis. All were initially treated with intravenous cefuroxime. After 2-3 d, when the fever had subsided and urinary culture had revealed growth of Gram-negative bacteria ( > 10(7) colony-forming units per litre), treatment was changed to oral administration of ceftibuten 200 mg b.i.d. or norfloxacin 400 mg b.i.d. for 10 d. The patients were followed for signs of bacterial or clinical relapse 7-14 d after the end of treatment. The initial clinical and bacteriological cure was excellent in both groups, but there were significantly fewer bacterial relapses after oral treatment with norfloxacin than with ceftibuten in acute febrile pyelonephritis initially treated with intravenous cefuroxime. The causal strain was eradicated in 75% of patients (73% of males, 76% of females) in the ceftibuten group and in 89% of patients (94% of males, 85% of females) in the norfloxacin group. The relative frequency of eradication was 0.84 (p < 0.05; 95%, confidence interval 0.74-0.97). Adverse events were reported by 47% of the patients in the ceftibuten group and by 38% in the norfloxacin group. This difference was not significant, but diarrhoea or loose stools occurred more frequently in the ceftibuten group.

Acute Disease↗
PubMed2000

Distinct frequency preferences of different types of rat hippocampal neurones in response to oscillatory input currents.

1. Coherent network oscillations in several distinct frequency bands are seen in the hippocampus of behaving animals. To investigate how different neuronal types within this network respond to oscillatory inputs we made whole-cell current clamp recordings from three different types of neurones in the CA1 region of rat hippocampal slices: pyramidal cells, fast-spiking interneurones and horizontal interneurones, and recorded their response to sinusoidal inputs at physiologically relevant frequencies (1-100 Hz). 2. Pyramidal neurones showed firing preference to inputs at theta frequencies (range 2-7 Hz; n = 30). They showed subthreshold resonance in the same frequency range (2-7 Hz; mean 4.1 +/- 0.4 Hz; n = 19). 3. Interneurones differed in their firing properties. Horizontal interneurones in the stratum oriens showed firing preference to inputs at theta frequencies (range 1.5-10 Hz; n = 10). These interneurones also showed resonance at low frequencies (range 1-5 Hz; mean 2.4 +/- 0.5 Hz; n = 7). In contrast, fast-spiking interneurones with cell bodies in the pyramidal cell layer fired preferentially at input frequencies in the gamma band (range 30-50 Hz; n = 10/12). These interneurones showed resonance at beta-gamma frequencies (10-50 Hz; mean 26 +/- 5 Hz; n = 7/8). 4. Thus, in the hippocampus, different types of neurones have distinct frequency preferences. Therefore, in the CA1 layer of the hippocampal network, a compound oscillatory input may be segregated into distinct frequency components which are processed locally by distinct types of neurones.

Action Potentials↗
PubMed2000

Natural patterns of activity and long-term synaptic plasticity.

Long-term potentiation (LTP) of synaptic transmission is traditionally elicited by massively synchronous, high-frequency inputs, which rarely occur naturally. Recent in vitro experiments have revealed that both LTP and long-term depression (LTD) can arise by appropriately pairing weak synaptic inputs with action potentials in the postsynaptic cell. This discovery has generated new insights into the conditions under which synaptic modification may occur in pyramidal neurons in vivo. First, it has been shown that the temporal order of the synaptic input and the postsynaptic spike within a narrow temporal window determines whether LTP or LTD is elicited, according to a temporally asymmetric Hebbian learning rule. Second, backpropagating action potentials are able to serve as a global signal for synaptic plasticity in a neuron compared with local associative interactions between synaptic inputs on dendrites. Third, a specific temporal pattern of activity--postsynaptic bursting--accompanies synaptic potentiation in adults.

Action Potentials↗
PubMed1999

Rapid report: postsynaptic bursting is essential for 'Hebbian' induction of associative long-term potentiation at excitatory synapses in rat hippocampus.

1. The biologically relevant rules of synaptic potentiation were investigated in hippocampal slices from adult rat by mimicking neuronal activity seen during learning behaviours. Synaptic efficacy was monitored in two separate afferent pathways among the Schaffer collaterals during intracellular recording of CA1 pyramidal neurones. The effects of pairing presynaptic single spikes or bursts with postsynaptic single spikes or bursts, repeated at 5 Hz ('theta' frequency), were compared. 2. The pairing of ten single evoked excitatory synaptic events with ten postsynaptic single action potentials at 5 Hz, repeated twelve times, failed to induce synaptic enhancement (EPSP amplitude 95% of baseline amplitude 20 min after pairing; n = 5). In contrast, pairing the same number of action potentials, but clustered in bursts, induced robust synaptic potentiation (EPSP amplitude 163%; P < 0.01, Student's t test; n = 5). This potentiation was input specific, long lasting ( > 1 h; n = 3) and its induction was blocked by an antagonist at NMDA receptors (20-50 microM D(-)-2-amino-5-phosphonopentanoic acid; EPSP amplitude 109%; n = 6). 3. Presynaptic bursting paired with postsynaptic single action potentials did not induce input specific synaptic change (113 % in the test input vs. 111 % in the control; n = 8). In contrast, postsynaptic bursting when paired with presynaptic single action potentials was sufficient to induce synaptic potentiation when the presynaptic activity preceded the postsynaptic activity by 10 ms (150 vs. 84 % in the control input; P < 0.01; n = 10). 4. These results indicate that, under our conditions, postsynaptic bursting activity is necessary for associative synaptic potentiation at CA1 excitatory synapses in adult hippocampus. The existence of a distinct postsynaptic signal for induction of synaptic change calls for refinement of the common interpretation of Hebb's rule, and is likely to have important implications for our understanding of cortical network operation.

2-Amino-5-phosphonovalerate↗
PubMed1998

Cholinergic induction of network oscillations at 40 Hz in the hippocampus in vitro.

Acetylcholine is vital for cognitive functions of the brain. Although its actions in the individual cell are known in some detail, its effects at the network level are poorly understood. The hippocampus, which receives a major cholinergic input from the medial septum/diagonal band, is important in memory and exhibits network activity at 40 Hz during relevant behaviours. Here we show that cholinergic activation is sufficient to induce 40-Hz network oscillations in the hippocampus in vitro. Oscillatory activity is generated spontaneously in the CA3 subfield and can persist for hours. During the oscillatory state, principal neurons fire action potentials that are phase-related to the extracellular oscillation, but each neuron fires in only a small proportion of the cycles. Both excitatory and inhibitory synaptic events participate during the network oscillation in a precise temporal pattern. These results indicate that subcortical cholinergic input can control hippocampal memory processing by inducing fast network oscillations.

Acetylcholine↗
PubMed1998

Importance of the intracellular domain of NR2 subunits for NMDA receptor function in vivo.

NMDA receptors, a class of glutamate-gated cation channels with high Ca2+ conductance, mediate fast transmission and plasticity of central excitatory synapses. We show here that gene-targeted mice expressing NMDA receptors without the large intracellular C-terminal domain of any one of three NR2 subunits phenotypically resemble mice made deficient in that particular subunit. Mice expressing the NR2B subunit in a C-terminally truncated form (NR2B(deltaC/deltaC) mice) die perinatally. NR2A(deltaC/deltaC) mice are viable but exhibit impaired synaptic plasticity and contextual memory. These and NR2C(deltaC/deltaC) mice display deficits in motor coordination. C-terminal truncation of NR2 subunits does not interfere with the formation of gateable receptor channels that can be synaptically activated. Thus, the phenotypes of our mutants appear to reflect defective intracellular signaling.

Amino Acid Sequence↗
PubMed1998

A model of hippocampal memory encoding and retrieval: GABAergic control of synaptic plasticity.

The current view of the role of GABAergic interneurones in cortical-network function has shifted from one of merely dampening neuronal activity to that of an active role in information processing. In this review, we explore a potential role of hippocampal GABAergic interneurones in providing spatial and temporal conditions for modifications of synaptic weights during hippocampus-dependent memory processes. We argue that knowledge of spatiotemporal activity patterns in distinct classes of interneurone is essential to understanding the cellular mechanisms underlying learning and memory.

Electroencephalography↗
PubMed1998

Association between the low threshold calcium spike and activation of NMDA receptors in guinea-pig substantia nigra pars compacta neurons.

The aim of this study was to examine the interaction between N-methyl-D-aspartate (NMDA) receptor activation and the low threshold calcium spike (LTS) of phasically firing neurons in the rostral part of the substantia nigra pars compacta (SNpc) in mid-brain slices. Bath perfusion of 10 microM NMDA gradually increased the LTS area and the effect reached a maximum after 6 min of perfusion. This enhancement of the LTS by NMDA was blocked both by a competitive and non-competitive NMDA receptor antagonist, 50 microM D-AP5 and 10 microM MK801, respectively, demonstrating that this effect of NMDA was mediated through NMDA receptors. Prolonged exposure to increasing concentrations of NMDA (0.1-100 microM) progressively decreased the LTS area. The higher doses led to an irreversible marked depolarization and decrease of the membrane resistance. These results suggest that the LTS of SNpc neurons can trigger a NMDA receptor-dependent response which may have physiological and pathological roles.

2-Amino-5-phosphonovalerate↗
PubMed1997

[Integration of preventive medicine in an emergency department. A pedagogic model for improvement of communication].

At the Medical Department, Telemark Central Hospital, a project has been going on for five years now to evaluate consultations in lifestyle groups in preference to individual consultations for persons with dyslipidemia. 363 persons were recruited to participate in a series of 5 group consultations at intervals of 3 months, each session to last for 2 hours. Altogether 1469 consultations were of this type. After the first session 79% said they preferred lifestyle group consultations, rather than spending their share of the allotted time on personal consultations, and after the fifth session 81%. The concept has been extended to include patients with chronic disease (asthma and chronic inflammatory bowel disease), with the principal aim of improving the patients' understanding of their disease, and showing them how to control it themselves. The project has attracted much attention, and a consultant in preventive medicine has recently been appointed to the staff. We think it important in terms of impact that the initiative to establish local expertise in preventive medicine emerged from a department that deals with emergency admissions due to lifestyle-related diseases.

Adolescent↗
PubMed1997

Effect, number and location of synapses made by single pyramidal cells onto aspiny interneurones of cat visual cortex.

1. Dual intracellular recordings were made from synaptically coupled pyramidal cell-to-interneurone pairs (n = 5) of the cat visual cortex in vitro. Pre- and postsynaptic neurones were labelled with biocytin, followed by correlated light and electron microscopic analysis to determine all sites of synaptic interaction. 2. Pyramidal neurones in layers II-III elicited monosynaptic EPSPs in three distinct classes of smooth dendritic local-circuit neurones, namely basket cells (n = 3), a dendrite-targeting cell (n = 1) and a double bouquet cell (n = 1). Unitary EPSPs in basket cells were mediated by one, two, and two synaptic junctions, whereas the pyramid-to-dendrite-targeting cell and pyramid-to-double bouquet cell interaction were mediated by five and seven synaptic junctions, respectively. Recurrent synaptic junctions were found on all somato-dendritic compartments, with a tendency to be clustered close to the soma on the double bouquet and dendrite-targeting cells. The latter interneurones were reciprocally connected with pyramidal cells. 3. Unitary EPSPs had an average peak amplitude of 1005 +/- 518 microV, fast rise times (10-90%; 0.67 +/- 0.25 ms) and were of short duration (at half-amplitude, 4.7 +/- 1.0 ms). Their decay was monoexponential (tau = 7.8 +/- 4.3 ms) at hyperpolarized membrane potentials and appeared to be shaped by passive membrane properties (tau = 9.2 +/- 8.5 ms). All parameters of concomitantly recorded spontaneous EPSPs were remarkably similar (mean amplitude, 981 +/- 433 microV; mean rise time, 0.68 +/- 0.18 ms; mean duration, 4.7 +/- 1.7 ms). 4. In all three pyramidal-to-basket cell pairs, closely timed (10-50 ms) pairs of presynaptic action potentials resulted in statistically significant paired-pulse depression, the mean of the averaged second EPSPs being 80 +/- 11% of the averaged conditioning event. The overall degree of paired-pulse modulation was relatively little affected by either the amplitude of the preceding event or the inter-event interval. 5. The probability density function of the peak amplitudes of the unitary EPSPs could be adequately fitted with a quantal model. Without quantal variance, however, the minimum number of components in the model, excluding the failures, exceeded the number of electron microscopically determined synaptic junctions for all five connections. In contrast, incorporating quantal variance gave a minimum number of components which was compatible with the number of synaptic junctions, and which fitted the data equally well as models incorporating additional components but no quantal variance. For this model with quantal variance with the minimum number of components the estimate of the quantal coefficient of variation ranged between 0.33 and 0.46, and the corresponding quantal sizes ranged between 260 and 657 microV. The peak EPSP amplitudes in two of the four connections with more than one synaptic junction could be adequately described by a uniform binomial model for transmitter release. 6. In conclusion, at least three distinct interneurone classes receive local excitatory pyramidal cell input which they relay to different compartments on their postsynaptic target neurones. The reliability of transmission is high, but the fast time course of the EPSPs constrains their temporal summation. Due to the relatively small amplitude of unitary EPSPs several convergent inputs will therefore be required to elicit suprathreshold responses.

Action Potentials↗
PubMed1997

Economic analysis of treatment with roxithromycin in comparison with erythromycin in patients with lower respiratory tract infections.

A number of new antibiotics have lately become available for treatment of lower respiratory tract infections in out-patients. The new drugs are generally more expensive than the older ones, which might be justified by better effects, improved safety, or by other advantages. In this study, a retrospective economic analysis has been made using data from a previous trial comparing a new macrolide, roxithromycin, with an older 1, erythromycin stearate in the treatment of lower respiratory tract infections. The trial was multicentre, double blind, randomized and comparative. There were no significant differences in efficacy between treatments, although the cure rate was higher for roxithromycin, 85% vs 79% for erythromycin. 20/39 of the erythromycin-treated patients reported adverse events, vs 7/40 roxithromycin-treated subjects, a highly significant difference. More detailed information was obtained by reviewing the medical records of the participants, and from questionnaires distributed to the 3 centres that had included patients in the trial. Additional visits were found necessary for 4 patients treated with erythromycin and for 1 using roxithromycin. Using the healing rates in the present investigation, and including costs for initial drug treatments, second consultations, and failed therapy, average cost-effectiveness (SEK/patient cured) was 409 for roxithromycin-treated patients, and 488 for erythromycin-treated. Roxithromycin should then be cheaper than erythromycin stearate. With the same healing rate, roxithromycin would be less cost-effective, but indirect costs and effects on quality of life are not then taken into account.

Anti-Bacterial Agents↗
PubMed1996

Quantal properties of spontaneous EPSCs in neurones of the guinea-pig dorsal lateral geniculate nucleus.

1. Spontaneous non-NMDA glutamate receptor-mediated EPSCs were recorded with the whole-cell patch-clamp technique from twenty-six neurones in the dorsal lateral geniculate nucleus in thalamic slices from guinea-pig. 2. Amplitude distributions of the EPSCs were skewed towards larger values. The skewness could be accounted for by multiquantal properties. The multiquantal properties were most clearly demonstrated in four cells that had prominent peaks in the amplitude distribution, and peak separation approximately corresponding to the modal value. The amplitude distribution for all cells could be adequately fitted by a quantal model consisting of a sum of Gaussians with means equal to integer multiples of a quantal unit. The variance of each Gaussian was equal to the sum of the noise variance of the recordings and an additional non-negative variance which increased linearly with the number of the Gaussian in the series. The estimated mean quantal size was 152 +/- 37 pS. The estimated mean quantal coefficient of variation was 15%. Addition of tetrodotoxin did not significantly change any of the quantal parameters (n = 5). 3. The waveform of the EPSCs was similar for small and large events, and similar to that of events evoked by stimulation of retinal input fibres. There was a positive correlation between peak amplitude and rise time. This is the opposite of that expected if differences in electrotonic distances were to explain differences in amplitude. 4. The spontaneous EPSCs occurred randomly at an average frequency of 3.1 Hz. The events with amplitudes approximately equal to multiples of the quantal size were, in most cells, more numerous than could be accounted for by coincidence of randomly occurring events of quantal size. 5. The results indicate that spontaneous EPSCs can reflect more than a single quantum, and suggest that quantal events may be coupled due to action potential-independent near-synchronous multiquantal release of transmitter.

2-Amino-5-phosphonovalerate↗
PubMed1995

Synchronization of neuronal activity in hippocampus by individual GABAergic interneurons.

SYNCHRONIZATION of neuronal activity is fundamental in the operation of cortical networks. With respect to an ongoing synchronized oscillation, the precise timing of action potentials is an attractive candidate mechanism for information coding. Networks of inhibitory interneurons have been proposed to have a role in entraining cortical, synchronized 40-Hz activity. Here we demonstrate that individual GABAergic interneurons can effectively phase spontaneous firing and subthreshold oscillations in hippocampal pyramidal cells at 0 frequencies (4-7 Hz). The efficiency of this entrainment is due to interaction of GABAA-receptor-mediated hyperpolarizing synaptic events with intrinsic oscillatory mechanisms tuned to this frequency range in pyramidal cells. Moreover, this GABAergic mechanism is sufficient to synchronize the firing of pyramidal cells. Thus, owing to the divergence of each GABAergic interneuron, more than a thousand pyramidal cells may share a common temporal reference established by an individual interneuron.

Action Potentials↗