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Biomedical subjects

M Atzori

Publications and source records attributed to M Atzori.

14 recordsLinked to original sources
PubMed2001

Mobilization of calcium from intracellular stores, potentiation of neurotransmitter-induced calcium transients, and capacitative calcium entry by 4-aminopyridine.

In this study we analyzed the effect of 4-aminopyridine (4-AP) on free cytosolic calcium concentration ([Ca(2+)](i)) in basal conditions, after stimulation with neurotransmitters, and during capacitative calcium entry. Using fura-2 ratiometric calcium imaging, we found that 4-AP increased [Ca(2+)](i) in type I astrocytes, neurons, and in skeletal muscle cells. The [Ca(2+)](i) elevation induced by 4-AP was concentration-dependent and consisted of two phases: the first was dependent on intracellular calcium mobilization, and the second was dependent on extracellular calcium influx. 4-AP also increased the second messenger inositol trisphosphate in both neurons and astrocytes. In astrocytes, 4-AP treatment potentiated the sustained phase of the [Ca(2+)](i) elevation induced by ATP and bradykinin. In addition, capacitative calcium entry was potentiated severalfold by 4-AP, in astrocytes and muscle cells but not in neurons. These effects of 4-AP were completely and promptly reversible. 4-AP blocked voltage-sensitive K(+) currents in astrocytes. However, voltage-sensitive K(+) channel blockers inhibiting these currents did not affect agonist-induced calcium transients or capacitative calcium entry, indicating that 4-AP effects on [Ca(2+)](i) were not caused by the blockade of voltage-gated K(+) channels. We conclude that 4-AP is able to affect calcium homeostasis at multiple levels, from increasing basal [Ca(2+)](i) to potentiating capacitative calcium entry. The potentiation of capacitative calcium entry in astrocytes or muscle cells may explain some of the therapeutic activities of 4-AP as a neurotransmission enhancer.

4-Aminopyridine↗
PubMed2001

Differential synaptic processing separates stationary from transient inputs to the auditory cortex.

Sound features are blended together en route to the central nervous system before being discriminated for further processing by the cortical synaptic network. The mechanisms underlying this synaptic processing, however, are largely unexplored. Intracortical processing of the auditory signal was investigated by simultaneously recording from pairs of connected principal neurons in layer II/III in slices from A1 auditory cortex. Physiological patterns of stimulation in the presynaptic cell revealed two populations of postsynaptic events that differed in mean amplitude, failure rate, kinetics and short-term plasticity. In contrast, transmission between layer II/III pyramidal neurons in barrel cortex were uniformly of large amplitude and high success (release) probability (Pr). These unique features of auditory cortical transmission may provide two distinct mechanisms for discerning and separating transient from stationary features of the auditory signal at an early stage of cortical processing.

Action Potentials↗
PubMed2000

H2 histamine receptor-phosphorylation of Kv3.2 modulates interneuron fast spiking.

Histamine-containing neurons of the tuberomammilary nucleus project to the hippocampal formation to innervate H1 and H2 receptors on both principal and inhibitory interneurons. Here we show that H2 receptor activation negatively modulates outward currents through Kv3.2-containing potassium channels by a mechanism involving PKA phosphorylation in inhibitory interneurons. PKA phosphorylation of Kv3.2 lowered the maximum firing frequency of inhibitory neurons, which in turn negatively modulated high-frequency population oscillations recorded in principal cell layers. All these effects were absent in a Kv3.2 knockout mouse. These data reveal a novel pathway for histamine-dependent regulation of high-frequency oscillations within the hippocampal formation.

1-Methyl-3-isobutylxanthine↗
PubMed1998

Nitric oxide sensitive depolarization-induced hyperpolarization: a possible role for gap junctions during development.

Electrical coupling is a widespread feature of developing neuronal circuits and it contributes to the generation of patterned activity. In the developing rat hippocampus, release of GABA by coactive hilar interneurones generates widespread synchronized activity. Here it is shown that hilar interneurones strongly rectify in the outward direction when depolarized. This depolarization-induced hyperpolarization, abolished by gap junction uncouplers, is modulated by nitric oxide. This phenomenon might represent a current-shunting mechanism of the excess current by providing functional inhibition at a developmental stage when GABA is excitatory. Spatial buffering of the current might represent an osmotic mechanism for growth and differentiation.

Anesthetics, Inhalation↗
PubMed1997

A pacemaker current in dye-coupled hilar interneurons contributes to the generation of giant GABAergic potentials in developing hippocampus.

The establishment of synaptic connections and their refinement during development require neural activity. Increasing evidence suggests that spontaneous bursts of neural activity within an immature network are mediated by gamma-aminobutyric acid via a paradoxical excitatory action. Our data show that in the developing hippocampus such synchronous burst activity is generated in the hilar region by transiently coupled cells. These cells have been identified as neuronal elements because they fire action potentials and they are not positive for the glial fibrillary acidic protein staining. Oscillations in hilar cells are "paced" by a hyperpolarization-activated current, with properties of Ih. Coactivated interneurons synchronously release GABA, which via its excitatory action may serve a neurotrophic function during the refinement of hippocampal circuitry.

Aging↗
PubMed1996

Postsynaptic induction of mossy fibre long term depression in developing rat hippocampus.

The whole cell configuration of the patch clamp technique was used to study the mechanisms of induction of long term depression (LTD) occurring at the mossy fibre-CA3 synapse between postnatal (P) day 6 and P13. In control conditions, when two pulses were delivered to the mossy fibres with an interval of 50 ms a potentiation of the EPSC evoked by the second pulse associated with a reduction in the number of failures was observed. Tetanization of the mossy fibres induced LTD of the responses to the first and second stimulus without affecting the paired pulse facilitation. Loading the postsynaptic cell with BAPTA prevented the induction of LTD but did not modify the paired pulse facilitation, suggesting that LTD induction occurs at the postsynaptic site.

Animals↗
PubMed1996

Pyramidal cells and stratum lacunosum-moleculare interneurons in the CA1 hippocampal region share a GABAergic spontaneous input.

Patch-clamp technique was used in the CA1 region of the hippocampal rat slice preparation in order to perform a comparison between synaptic GABAergic spontaneous postsynaptic currents (sPSCs) recorded from pyramidal cells (PCs) of stratum pyramidale (SP) and interneurons of stratum-lacunosum moleculare (SL-M INs). GABAergic sPSCs from PCs and from SL-M INs displayed similar frequency (0.75 +/- 0.26 Hz vs. 0.53 +/- 0.11 Hz, respectively), amplitude (34.6 +/- 5.0 pA vs. 39.6 +/- 4.1 pA), rise-time (2.9 +/- 0.4 ms vs. 3.2 +/- 0.3 ms), and decay-time (31.7 +/- 1.5 vs. 32.3 +/- 2.4). Agonists of receptors for endogenously released transmitters were bath-applied to induce variations in the frequency of sPSCs. Spontaneous PSC frequency increased after carbachol and trans-1-aminocyclopentane-1,3-dicarboxilic acid (t-ACPD), whereas it decreased after 5-hydroxy-tryptamine (5-HT) and baclofen in both classes of cells. Cross-correlation analysis of double-patch recordings (one PC and one SL-M IN) revealed 4.4 times as many coincident events as would be expected at random. The ratio between measured and random coincidences did not vary when the sPSCs frequency was increased. These results suggest that the same class of spontaneously active GABAergic cells impinge both on PCs and on SL-M INs, exerting control over them by varying the level of released GABA.

Animals↗
PubMed1996

Effects of thyrotropin-releasing hormone on GABAergic synaptic transmission of the rat hippocampus.

The effect of thyrotropin-releasing hormone (TRH), a neuropeptide physiologically present in the mammalian hippocampus, on spontaneous, miniature and evoked GABAergic postsynaptic currents was investigated using whole-cell patch-clamp recording from pyramidal cells and interneurons of the rat hippocampal thin slice preparation. Bath application of 10 microM TRH induced an increase in the frequency of spontaneous postsynaptic currents from 1.07 +/- 0.68 to 3.16 +/- 0.73 Hz in pyramidal neurons and interneurons of the stratum lacunosum-moleculare (SL-M). In tetrodotoxin solution TRH did not change miniature postsynaptic currents. Application of TRH to minislices containing only the CA1 region still produced an increase in the spontaneous postsynaptic current frequency, indicative of an action by TRH upon a GABAergic circuitry. Paired recordings from one pyramidal cell and one stratum lacunosum moleculare interneuron displayed synchronous events whose frequency rose after TRH application, suggestive of a common, TRH-sensitive input. In a small subset of cells TRH induced the appearance of highly rhythmic large postsynaptic currents at a frequency of approximately 2 Hz, as confirmed by autocorrelation analysis. Postsynaptic currents electrically evoked by focal stimulation of stratum lacunosum-moleculare were depressed from 90 +/- 27 to 44 +/- 15 pA after application of TRH. This phenomenon was solely due to an increase in the number of synaptic failures. It is proposed that the effect of TRH on the GABAergic system was primarily exerted on a subset of interneurons controlling the activity of pyramidal cells as well as stratum lacunosum-moleuclare interneurons.

Animals↗
PubMed1994

Cl- transporter block enhances GABAergic spontaneous activity in rat hippocampal CA3 cells.

Chloride-cation Transporter Blockers (CTBs) furosemide and ammonium were used to test the effects of changes in the internal [Cl-] on the spontaneous and miniature GABAergic post-synaptic currents (PSCs) of CA3 pyramidal cells of rat hippocampal slices with the whole-cell patch technique. Application of CTBs in the presence of kynurenic acid raised (65 +/- 21%) the frequency of GABAergic spontaneous PSCs leaving unchanged the miniature frequency, indicating that the increase in synaptic activity was caused by interneurone firing. Partial removal of external chloride yielded the same effect, suggesting that ECl contributes to the resting potential of interneurones. PSC rise times were prolonged and their mean amplitude was lowered by furosemide as well as the response to exogenous muscimol, confirming that furosemide exerts some GABAA receptor antagonism.

Animals↗
PubMed1994

Non-monotonic decay of excitatory synaptic transmission in the frog optic tectum following repetitive stimulation of the optic nerve in vitro.

The monosynaptic field excitatory postsynaptic potentials (EPSPs) evoked in the optic tectum of the frog (Rana remporaria) in vitro by different patterns of stimulation of the contralateral optic nerve were studied using extracellular recording. Pulse trains at frequencies of less than or equal to 0.033 Hz elicited field potentials of stable amplitude, whereas in the range 0.33-1.0 Hz EPSPs showed a depression in the first few responses subsequent to the first one, followed by a partial recovery and a final decline to a steady level. When the interpulse interval was less than 200 ms, paired-pulse monosynaptic facilitation was found. Decrease in the external Ca2+ concentration, or in the stimulation intensity or application of picrotoxin reversibly produced a monotonically decreasing EPSP amplitude, suggesting that a local neuronal circuit was controlling the development of synaptic fatigue. A simple model based on the combined effects of depletion of excitatory transmitter stores plus activation of a local inhibitory circuit was found to provide a simulation which closely resembled the experimentally observed pattern of synaptic fatigue. The present study suggests that an inhibitory synaptic process contributed to the non-monotonic decay of excitatory transmission in the frog optic tectum, following repetitive stimulation of the optic nerve.

Animals↗
PubMed1993

NMR studies of oligosaccharides derived from hyaluronate: complete assignment of 1H and 13C NMR spectra of aqueous di- and tetra-saccharides, and comparison of chemical shifts for oligosaccharides of increasing degree of polymerisation.

A series of oligosaccharides was prepared from hyaluronate by depolymerisation with bovine testicular hyaluronidase. Complete assignment of the 1H and 13C NMR spectra was obtained for the disaccharide, the tetrasaccharide, and the NaBH4-treated tetrasaccharide, by using various 1D and 2D NMR methods. The 1H assignments for the tetrasaccharide differ from the incomplete data reported recently (ref. 11). The 13C NMR spectra of the aqueous di-, tetra-, hexa-, and octa-saccharides of this series show that all resonances, apart from those subject to obvious end effects, have chemical shifts comparable to those of the corresponding resonances of hyaluronate in D2O. The observed 13C chemical shifts suggests that cooperative intramolecular hydrogen bonds probably play a minor role in determining the conformation of hyaluronate in water.

Animals↗
PubMed1992

1H- and 13C-NMR studies of solutions of hyaluronic acid esters and salts in methyl sulfoxide: comparison of hydrogen-bond patterns and conformational behaviour.

The 1H- and 13C-NMR spectra of the ethyl and benzyl esters and the tetrabutylammonium and tetraethylammonium salts of hyaluronic acid [[symbol: see text]2)-beta-D-GcpA+-1----3)-beta-D-GlcpNAc-(1[symbol: see text]n] in Me2SO-d6 have been assigned using 1D and 2D techniques. The chemical shifts of the resonance of GlcNAc C-3 suggest that the relative orientations of the monosaccharides at the (1----3) linkage in the esters and salts are different. Small differences in the chemical shifts of the resonance GlcA C-4 suggest only a slight conformational variation around the (1----4) linkage. The 13C-NMR data also suggest similarities in conformation between the esters in Me2SO-d6 and the salts in water. The chemical shifts of the 1H resonances for NH and OH groups and their temperature dependence for the esters and salts in Me2SO reveal markedly stronger inter-residue hydrogen bonds between the carboxyl and NH groups and between HO-4 of GlcA and O-5 of GlcNAc for the salts. The 3J2,NH values indicate a slightly different orientation for the acetamido group. For solutions in Me2SO, the higher segmental flexibility of the esters is supported by the line widths, whereas the reduced viscosity for the tetrabutylammonium salt showed a sigmoidal concentration dependence and suggests association of chains which could contribute to the segmental rigidity. The linear concentration dependence for the benzyl ester suggests a higher overall flexibility without chain association.

Carbohydrate Conformation↗