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Biomedical subjects

U Frey

Publications and source records attributed to U Frey.

At least 73 records · Page 4Linked to original sources
PubMed1996

Influence of actinomycin D, a RNA synthesis inhibitor, on long-term potentiation in rat hippocampal neurons in vivo and in vitro.

1. Hippocampal long-term potentiation (LTP) may serve as an elementary process underlying certain forms of learning and memory in vertebrates. As is the case with behavioural memory, hippocampal LTP in the rat CA1 region and in the dentate gyrus occurs in stages, which can be separated by an inhibitor of RNA synthesis. 2. Experiments have been performed in two brain regions, in the hippocampal CA1 region in vitro and in the dentate gyrus in vivo. 3. Maintenance of hippocampal LTP in the CA1 region in vitro was influenced by the RNA synthesis inhibitor actinomycin D from 4 h onwards. 4. The effect of actinomycin D on the time course of the population spike potentiation was more pronounced than the effect on the time course of the EPSP component, suggesting different mechanisms for the two forms of potentiation. 5. Intrahippocampal and intracerebroventricular injection of actinomycin D into rats prevented a late stage of LTP in the dentate gyrus in vivo measured as the population spike amplitude. 6. Since actinomycin D was only effective in influencing the maintenance of LTP when applied before tetanization, the requirement for transcription during LTP may have a critical time window. 7. Actinomycin D influenced the maintenance of LTP specifically, since the drug did not alter any potentials in control experiments after its removal or when it was administered shortly after tetanization. A second, structurally different RNA synthesis inhibitor, 5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole, mimicked the effect of actinomycin D in vitro.

Animals↗
PubMed1995

Somatodendritic expression of an immediate early gene is regulated by synaptic activity.

Trans-synaptic activation of gene expression is linked to long-term plastic adaptations in the nervous system. To examine the molecular program induced by synaptic activity, we have employed molecular cloning techniques to identify an immediate early gene that is rapidly induced in the brain. We here report the entire nucleotide sequence of the cDNA, which encodes an open reading frame of 396 amino acids. Within the hippocampus, constitutive expression was low. Basal levels of expression in the cortex were high but can be markedly reduced by blockade of N-methyl-D-aspartate receptors. By contrast, synaptic activity induced by convulsive seizures increased mRNA levels in neurons of the cortex and hippocampus. High-frequency stimulation of the perforant path resulted in long-term potentiation and a spatially confined dramatic increase in the level of mRNA in the granule cells of the ipsilateral dentate gyrus. Transcripts were localized to the soma and to the dendrites of the granule cells. The dendritic localization of the transcripts offers the potential for local synthesis of the protein at activated postsynaptic sites and may underlie synapse-specific modifications during long-term plastic events.

Amino Acid Sequence↗
PubMed1995

Interrelationship between postocclusional oscillatory pressure transients and standard lung function in healthy and asthmatic children.

We studied the correlation between characteristics of the postocclusional oscillatory airway opening pressure transients after flow interruption and body height, the degree of pulmonary hyperinflation [measured by thoracic gas volume (TGV)], and the degree of airway obstruction [measured by airway resistance (Raw)] and maximal expiratory flow at 50% vital capacity (MEF50) in 10 healthy and 50 asthmatic children age 7-16 years. Focusing on the damped oscillatory change in pressure, the first derivative of the shutter curve was analyzed, featuring a natural frequency fO and damping factor d in the time domain, and frequency FFS and power AFS in the frequency domain. A maximal frequency was found at approximately 80 Hz without a two peak distribution as described in dogs. Multiple linear forward step analysis revealed that omega O (the undamped, natural frequency) and AFS were related to body height (P < 0.001). The damping factor d (independent of body height) was related to TGV and MEF50 (P < 0.001), and FFS to Raw (P < 0.001). The analysis of the postocclusional pressure transients after airflow interruption provides information on the resistive, elastic and inertive properties of the thoraco-pulmonary system. The measurements obtained are influenced by the end-expiratory resting level (or the degree of pulmonary hyperinflation) and the degree of airway obstruction.

Adolescent↗
PubMed1995

Pressure oscillations after flow interruption in relation to lung mechanics.

The value of interrupter resistance measurements has been questioned because these depend on equilibration between alveolar (PA) and mouth pressure (PAO), which may not occur during airway obstruction or in measurements in children. In order to determine whether airway geometry and its interaction with the lung volume can be obtained without complete pressure equilibration, the postocclusional oscillatory airway opening pressure transients PAO(t) after flow interruption were studied in comparison to airway resistance (RAW), lung volumes (TGV, VC) and MEF50 in 9 healthy children (7-14 y) and 5 adults (28-37 y) in both time and frequency domains. The frequency of pressure oscillations was correlated to TGV (p < 0.01). Its damping properties (d) were correlated to MEF50 (p < 0.005). Performing airflow interruptions in the same subject showed that d increased at low lung volumes. During bronchial challenge test, d significantly increased with carbachol and decreased with salbutamol, whereas the frequency decreased with carbachol and increased with salbutamol. Therefore, the analysis of postocclusional pressure oscillations can be used to assess relative changes in airway mechanics and its interaction with lung volume during bronchial challenge tests in patients such as children with poor cooperation.

Adolescent↗
PubMed1995

Asymptotic hippocampal long-term potentiation in rats does not preclude additional potentiation at later phases.

Hippocampal long-term potentiation may serve as an elementary process underlying certain forms of learning and memory in vertebrates. As is the case with behavioural memory, hippocampal long-term potentiation in the CA1 region and in the dentate gyrus exhibits distinct phases. These comprise a short-term early potentiation which lasts one to three hours and is independent of protein synthesis and is characterized in general by the activation of N-methyl-D-aspartate receptors and protein kinases; and a later, longer lasting phase, which can be separated by inhibitors of protein synthesis. Here, we report that the prior induction of long-term potentiation, both in the dentate gyrus in vivo and in the CA1-region in vitro, precludes further long-term but not short-term potentiation by means of a newly delivered conditioning stimulus to a subset of the same activated synapse population during the early stage (approximately 1-3 hours post tetanus). In contrast, a subsequent, long-lasting potentiation can be induced after the establishment of the late phase of potentiation (> 4 h). Thus, the system preserves the capacity for short-term potentiation immediately after potentiation, but the capacity for the induction of longer lasting plastic changes is recovered only after about four hours. Our results demonstrate that, once long-term potentiation has been established, hippocampal neurons do not lose their capacity for functional plasticity during certain phases of the maintenance of long-term potentiation.

Animals↗
PubMed1993

Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons.

Hippocampal long-term potentiation (LTP) is thought to serve as an elementary mechanism for the establishment of certain forms of explicit memory in the mammalian brain. As is the case with behavioral memory, LTP in the CA1 region has stages: a short-term early potentiation lasting 1 to 3 hours, which is independent of protein synthesis, precedes a later, longer lasting stage (L-LTP), which requires protein synthesis. Inhibitors of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) blocked L-LTP, and analogs of cAMP induced a potentiation that blocked naturally induced L-LTP. The action of the cAMP analog was blocked by inhibitors of protein synthesis. Thus, activation of PKA may be a component of the mechanism that generates L-LTP.

Action Potentials↗
PubMed1993

The interrupter technique--a renaissance of a non-invasive approach for lung function testing in infants and children.

The analysis of the postocclusional rapid oscillatory mouth pressure transients pao(t) after expiratory flow interruption during 100 ms features additional information to the conventional interrupter technique. The analysis focuses on the sudden oscillatory rise in pressure after flow interruption and the following damped oscillation. By calculating the first derivative of pao(t) ( = change in pressure), the frequency omega 0 and damping characteristic d of the pressure swings reflecting the inertive and elastic properties of the thoracopulmonary system can be computed. The interrelationship between omega 0 respectively d and different sizes of lung volume respectively characteristics of airway mechanics (airway resistance (Raw) and/or maximal expiratory flow at 50% vital capacity (MEF50)) was evaluated in 5 healthy adult subjects (28-37 y) and 10 healthy children (7-14 y). The measured frequency was statistically significantly related to lung volume (p < 0.05) and varied between 66 Hz in healthy adults and 91 Hz in children. The damping factor d increased with increasing airway resistance (n.s.) and decreasing MEF50 (p < 0.005). These findings add further arguments to the conjecture previously intimated that development of the viscoelastic properties of the lung are defined by characteristics of airway mechanics in close relationship to lung growth. In consequence, alterations in mechanical properties observed in diseased lungs have functionally closely be evaluated in relation to actual lung volumes (pulmonary hyperinflation, restrictive lung disease).

Adolescent↗
PubMed1993

Specific approach on dose-response curves to inhaled carbachol assessed by the interruption technique in children.

To determine significant thresholds obtained by bronchial challenge tests in children for assessment of bronchial reactivity, changes of respiratory resistance (Rint) induced by inhaled carbachol were evaluated in 20 asthmatic children (10 boys and 10 girls, mean age 9.1 +/- 2.8 y, range 5 to 15 y) and 20 healthy control children (10 boys and 10 girls, mean age 12.1 +/- 2.6 y, range 8 to 16 y). Baseline lung function was assessed by whole body plethysmography. The carbachol challenge test was performed by the interruption technique. The objectives were to search for the most predictable provocation dose (PD) according to statistical and practical considerations. The statistical argument is given by the condition that the target PD must definitively be out of the measurement error of baseline values. From the practical point of view, the object is to provoke the subjects the least amount possible. As thresholds of bronchial reactivity, the provocation doses inducing a 50%, 65%, 75%, or 100% increase in baseline Rint (PD50, PD65, PD75, PD100) were computed by a 4th power polynomial function analysis including data points of the entire dose-response curve. In comparison, a new threshold, the "variance based" provocation dose (PDvb), was defined as threshold to be definitively above the range of the baseline Rint variation before initiating challenge [PDvb > mean + 2 SD range of Rint(0)]. Although the PD50, PD65, PD75, and PD100 can be adequately computed by the 4th power function from the whole dose-response curve, comparison between the different provocation thresholds revealed that PDvb gives the best values to differentiate between healthy and asthmatic children (p < 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1991

The effect of dopaminergic D1 receptor blockade during tetanization on the expression of long-term potentiation in the rat CA1 region in vitro.

The effect of dopaminergic D1 receptor blockade on the expression of long-term potentiation (LTP) was investigated in the rat hippocampal CA1 region in vitro by extracellular recordings (by measuring the population spike amplitude and the field EPSP). The presence of the very selective D1 receptor blocker SCH 23390 at a concentration of 0.1 microM during tetanization with 3 trains of 100 impulses (100 Hz) resulted in a prevention of late LTP stages (greater than 1-2 h). When SCH 23390 was added to the bath medium immediately after tetanization, an influence on established LTP could not be observed during the first 3 h investigated.

Animals↗
PubMed1991

Enhanced sensitivity of "metabotropic" glutamate receptors after induction of long-term potentiation in rat hippocampus.

Stimulation of [3H]inositol monophosphate ([3H]InsP) formation by ibotenate or trans-1-aminocyclopentyl-1,3-dicarboxylic acid (t-ACPD) in rat hippocampal slices was enhanced after tetanic stimulation of the Schaffer collaterals projecting to the CA1 region (in vitro) or the perforant pathway projecting to the dentate gyrus (in freely moving animals). This effect was observed 5 h (but not 2 h) after long-term potentiation (LTP) induction and was abolished if tetanic stimulation was performed in the presence of specific antagonists of N-methyl-D-aspartate receptors. The delayed increase in excitatory amino acid-induced polyphosphoinositide (PPI) hydrolysis was accompanied by an enhanced responsiveness to norepinephrine, whereas the basal and carbamylcholine-stimulated [3H]InsP formation were unchanged. These results suggest that an increased activity of "metabotropic" glutamate receptors may contribute to the synaptic mechanisms enabling the late expression and or maintenance of LTP. Accordingly, LTP decayed more rapidly (within 5 h) in rats repeatedly injected with LiCl (60-120 mg/kg, i.p., for 10 days), a treatment that led to a reduced efficacy of ibotenate and norepinephrine in stimulating PPI hydrolysis in hippocampal slices.

Animals↗
PubMed1991

Short-term effect of albuterol, delivered via a new auxiliary device, in wheezy infants.

In a double-blind, placebo-controlled study, the response of lung function to albuterol, topically administered by a metered-dose inhaler (MD) through a baby-adapted auxiliary device, was evaluated in 36 wheezy infants (1.6 to 25.2 months of age; median 8.1 months). The auxiliary device contains an air chamber of 350 ml and two low-resistant valves separating the inspiratory from the expiratory line. After baseline lung function measurements by infant whole-body plethysmography, the patients were randomly assigned to inhale either three times two puffs albuterol (100 micrograms/puff) or three times two puffs placebo at 5-min intervals. Changes in the degree of pulmonary hyperinflation, estimated by thoracic gas volume (TGV) and/or in the degree of bronchial obstruction, estimated by thoracic gas volume (TGV) and/or in the degree of bronchial obstruction, estimated by airway conductance (Gaw), were measured at 5-min intervals for up to 30 min. TGV and Gaw were expressed as standard deviation scores (SDS) of values predicted, and patients improving TGV and/or Gaw more than 2 SD were considered responders. In comparison with placebo, a significant percentage improvement in TGV (by the mean 26 to 53%) and a significant percentage improvement in Gaw (by the mean 34 to 51%) could be found in the active treatment groups. The study documents the usefulness of a new auxiliary device for the administration of aerosolized bronchodilators to wheezy infants.

Aerosols↗
PubMed1990

Dopaminergic antagonists prevent long-term maintenance of posttetanic LTP in the CA1 region of rat hippocampal slices.

The involvement of dopaminergic mechanisms in the induction and maintenance of posttetanic long-term potentiation (LTP) was investigated on CA1 cells of rat hippocampal slices. The presence of the dopamine receptor blocker domperidone in a concentration of 1 microM during tetanization with 3 trains of 100 impulses (100 Hz) and a train interval of 10 min influences neither the synaptic transmission nor the induction of LTP. However, the potentiation of both the population spike and the population EPSP gradually decreases, thus significantly differing from control LTP about 4 h after initiation and reaching the level of non-tetanized controls about 7-8 h after tetanization. The simultaneous presence of 1 microM apomorphine during tetanization abolishes this effect of domperidone indicating the specific dopaminolytic nature of its action. Also the presence of the dopamine antagonists sulpiride and flupenthixol, respectively, in a concentration of 1 microM during tetanization likewise prevents the occurrence of the late LTP maintenance. The determination of [14C]dopamine in 2 min fractions from the superfused slices after preloading during a preincubation period revealed that a low frequency stimulation of the Schaffer collaterals with 0.33 Hz does not influence the spontaneous efflux of dopamine, whereas the tetanization with an impulse train of 100 Hz produces a significantly enhanced release. The observations suggest that dopaminergic influences during and immediately after tetanization at least additionally contribute to the induction of postsynaptic mechanisms subserving a late, long-lasting maintenance of potentiation. The results also support the assumed existence of different subsequent stages of LTP.

Animals↗
PubMed1989

Long-term potentiation induced in dendrites separated from rat's CA1 pyramidal somata does not establish a late phase.

In 14 transversal hippocampal slices from rats the extracellular field-EPSP (excitatory postsynaptic potential) in the dendritic region of the CA1 subfield was recorded after isolating the apical dendrites from their somata by microsurgical cuts through the proximal stratum radiatum. Contrary to intact slices which, after tetanic stimulation of the Schaffer collaterals, showed long-term potentiation (LTP) until the end of registration after 8-10 h, LTP declined in the isolated dendrites to baseline values after 3 h. It is concluded that de-novo protein synthesis in postsynaptic cell bodies might be necessary for the maintenance of late phases of LTP.

Action Potentials↗