Postsynaptic depolarisation enhances transmitter release and causes the appearance of responses at "silent" synapses in rat hippocampus

Recent data indicate that most "silent" synapses in the hippocampus are "presynaptically silent" due to low transmitter release rather than "postsynaptically silent" due to "latent" receptors of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid type (AMPARs). That synapses bearing only N-methyl-d-aspartate (NMDAR) receptors do exist is suggested by the decreased number of transmission failures during postsynaptic depolarisation and by the presence of NMDA-mediated excitatory postsynaptic currents (EPSCs) in synapses silent at rest. We tested whether these effects could be due to potentiated transmitter release at depolarised postsynaptic potentials rather than removal of Mg(2+) block from NMDARs. Using whole-cell recordings of minimal EPSCs from CA1 and CA3 neurones of hippocampal slices we confirmed decreased incidence of failures at +40 mV as compared with -60 mV. This effect was associated with a gradual increase of EPSC amplitude after switching to +40 mV and with a decrease of paired-pulse facilitation. In initially silent synapses, potentiation of pharmacologically isolated AMPAR-mediated EPSCs was still observed at +40 mV and this persisted after stepping back to -60 mV. All above effects were blocked when the cell was dialysed with the Ca(2+) chelator BAPTA (20 mM). These observations are difficult to reconcile with the "latent AMPAR" hypothesis and suggest an alternative explanation, namely that the reduction in failure rates at positive potentials is due to potentiation of transmitter release following Ca(2+) influx through NMDARs. Our results suggest that silent synapses can be mainly "presynaptically" rather than "postsynaptically silent" and thus increased transmitter release rather than insertion of AMPARs is a major mechanism of early long-term potentiation maintenance.     

Helicobacter pylori infection in childhood: results of management with ranitidine bismuth citrate plus amoxicillin and tinidazole

BACKGROUND AND AIMS: To verify whether a triple therapy bismuth citrate plus amoxicillin and tinidazole eradicates H. pylori infection in pediatric patients. METHODS: Fifty children (30 females; mean age 12.4 +/- 1.1 years, range 10-15 years) suffering from upper abdominal complaints and Helicobacter pylori (H. pylori)-associated gastroduodenal disease were treated with a 4 week course of ranitidine bismuth citrate (400 mg, twice daily) plus oral tinidazole (20 mg/kg) and amoxicillin (50 mg/kg) for the first 2 weeks. RESULTS: The endoscopic diagnoses were: esophagitis (seven cases), gastritis (six cases), gastroduodenitis (43 cases), duodenitis (one case), gastric ulcer (two cases) and duodenal ulcer (13 cases). Helicobacter pylori was eradicated in 40 (80%) patients and clinical improvement was noticed in 39 (78%) of symptomatic subjects. Duodenal ulcers were healed in all the children, but lymphoid nodular hyperplasia was persistent in all patients, independent of the H. pylori status. The potentially drug-related adverse events (blackening of the tongue, six patients; diarrhea, one patient; disturbance of taste, two patients) were registered in seven (14%) patients and dark stools were observed in 48 (96%) patients. No children withdrew from the study because of either side-effects or clinical laboratory changes. No patient had toxic levels of blood bismuth (values ranged between 2.1 and 5.4 microg/L, mean value 3.4 +/- 1.04 microg/L). CONCLUSIONS: Findings suggest that the present treatment regimen is effective enough in the resolution of H. pylori-associated peptic ulcer disease of childhood.     

Combining principal component and spectral analyses with the method of moments in studies of quantal transmission

This chapter considers methods for measurements of postsynaptic responses and simple approaches to the estimation of parameters of quantal release in synapses of the central nervous system of vertebrates. The use of these methods is illustrated by the analysis of single-fibre and “minimal” monosynaptic postsynaptic potentials (PSPs) or currents (PSCs) recorded from neurons of the frog spinal cord and rat hippocampus. First, we briefly discuss traditional methods of the response measurements using peak amplitudes or areas, further focusing on a novel method based on multivariate statistical techniques of the principal component analysis (PCA). This approach provides typically better signal-to-noise ratios and is able to separate two or more response components, which can arise due to activation of more than one presynaptic fibre, axon collaterals, receptor subtypes or spatially separated transmission sites. Second, spectral analysis is introduced as the method of choice to verify whether the amplitude fluctuations of the postsynaptic responses have a quantal nature and to obtain estimations of the “basic” quantal parameters, i.e. the quantal size (Q) and mean quantal content (m), without introducing assumptions on release statistics. Third, we show how the method of moments could be applied in the framework of the Poisson and binomial models to estimate the basic quantal parameters and parameters p and n, which reflect the release probability and maximum number of quanta released (or the number of effective release sites), respectively. Fourth, we show that the analysis of the moments can also be instrumental to reveal non-uniformity of release probabilities and compare how several competing models of neurotransmitter release fit to multiple experimental data sets.     

Low-frequency depression of synaptic responses recorded from rat visual cortex

To characterize the low-frequency depression (LFD) of synaptic transmission in the visual cortex, we recorded field potentials and minimal excitatory postsynaptic potentials (EPSPs) from layer II/III following intracortical stimulation at various frequencies in cortical slices of rats. Field potentials were stable at 0.017 Hz, but showed an amplitude depression at 0.033-0.1 Hz at stimulus intensity of 1.5 times the threshold for induction of the postsynaptic component and at 0.1-0.2 Hz at intensity of 1.2 times the threshold. The LFD was input-specific and its magnitude correlated with the stimulus frequency. An interruption of stimulation for 15 min yielded a nearly complete recovery from LFD. Minimal EPSPs tested at 0.1-1.7 Hz often showed LFD with similar features. However, some inputs were stable or even facilitated during repeated stimulation. At 0.1 and 0.2 Hz, >50% of inputs were stable, whereas 10% and 25% were depressed, respectively. At 0.5 and 1.7 Hz, LFD was observed in >60% and 80% of inputs, respectively. The magnitude of LFD strongly varied across inputs. In 3 of the 41 inputs analyzed, LFD was so strong that these inputs became virtually silent. Occurrence of responses to the second pulse in the paired-pulse paradigm when the first response was absent and recovery of depressed EPSPs following stimulus interruption or shift to a lower frequency suggest that these synapses were presynaptically silent due to a lowered probability of transmitter release. Altogether, the results indicate that testing intervals of <10 or even < or =30 s cannot be regarded as completely neutral. At the single-cell level, frequency-dependent changes were strongly heterogeneous across different inputs. LFD and its spontaneous recovery may underlie the previously described "post-rest" potentiation, and should be taken into account when considering information processing in cortical networks.