Building up the inhibitory synapses

2nonenoneCherubini E; Zacchi PCherubini, E; Zacchi,

Fluoxetine impairs GABAergic signaling in hippocampal slices from neonatal rats

Fluoxetine (Prozac), an antidepressant known to selectively inhibit serotonin reuptake, is widely used to treat mood disorders in women suffering from depression during pregnancy and postpartum period. Several lines of evidence suggest that this drug, which crosses the human placenta and is secreted into milk during lactation, exerts its action not only by interfering with serotoninergic but also with GABAergic transmission. GABA is known to play a crucial role in the construction of neuronal circuits early in postnatal development. The immature hippocampus is characterized by an early type of network activity, the so-called Giant Depolarizing Potentials (GDPs), generated by the synergistic action of glutamate and GABA, both depolarizing and excitatory. Here we tested the hypothesis that fluoxetine may interfere with GABAergic signaling during the first postnatal week, thus producing harmful effects on brain development. At micromolar concentrations fluoxetine severely depressed GDPs frequency (IC50 22 \u3bcM) in a reversible manner and independently of its action on serotonin reuptake. This effect was dependent on a reduced GABAergic (but not glutamatergic) drive to principal cells most probably from parvalbumin-positive fast spiking neurons. Cholecystokinin-positive GABAergic interneurons were not involved since the effects of the drug persisted when cannabinoid receptors were occluded with WIN55,212-2, a CB1/CB2 receptor agonist. Fluoxetine effects on GABAergic transmission were associated with a reduced firing rate of both principal cells and interneurons further suggesting that changes in network excitability account for GDPs disruption. This may have critical consequences on the functional organization and stabilization of neuronal circuits early in postnatal development. \ua9 2013 Cherubini and Caiati

Functional role of ambient GABA in refining neuronal circuits early in postnatal development

Early in development, \u3b3-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the mature brain, depolarizes and excites targeted neurons by an outwardly directed flux of chloride, resulting from the peculiar balance between the cation-chloride importer NKCC1 and the extruder KCC2. The low expression of KCC2 at birth leads to accumulation of chloride inside the cell and to the equilibrium potential for chloride positive respect to the resting membrane potential. GABA exerts its action via synaptic and extrasynaptic GABAA receptors mediating phasic and tonic inhibition, respectively. Here, recent data on the contribution of "ambient" GABA to the refinement of neuronal circuits in the immature brain have been reviewed. In particular, we focus on the hippocampus, where, prior to the formation of conventional synapses, GABA released from growth cones and astrocytes in a calcium- and SNARE (soluble N -ethylmaleimide-sensitive-factor attachment protein receptor)-independent way, diffuses away to activate in a paracrine fashion extrasynaptic receptors localized on distal neurons. The transient increase in intracellular calcium following the depolarizing action of GABA leads to inhibition of DNA synthesis and cell proliferation. Tonic GABA exerts also a chemotropic action on cell migration. Later on, when synapses are formed, GABA spilled out from neighboring synapses, acting mainly on extrasynaptic \u3b15, \u3b22, \u3b23, and \u3b3 containing GABAA receptor subunits, provides the membrane depolarization necessary for principal cells to reach the window where intrinsic bursts are generated. These are instrumental in triggering calcium transients associated with network-driven giant depolarizing potentials which act as coincident detector signals to enhance synaptic efficacy at emerging GABAergic and glutamatergic synapses. \ua9 2013 Cellot and Cherubini

Superradiance from BEC vortices: a numerical study

The scattering of sound wave perturbations from vortex excitations of Bose-Einstein condensates(BEC) is investigated by numerical integration of the associated Klein-Gordon equation. It is found that, at sufficiently high angular speeds, sound wave-packets can extract a sizeable fraction of the vortex energy through a mechanism of superradiant scattering. It is conjectured that this superradiant regime may be detectable in BEC experiments.Comment: 4 pages, 4 figure

Retrospective Preliminary Assessment of Routine Follow-Up Low-Field Magnetic Resonance Imaging in Dogs Presumptively Diagnosed With Discospondylitis

Background: The usefulness of routine follow-up Magnetic Resonance Imaging (MRI-2) in asymptomatic dogs treated for discospondylitis is unknown. Methods: This cross-sectional retrospective study investigated the features of MRI-2 in a heterogeneous group of dogs treated for discospondylitis, and if these were associated with the presence or absence of clinical signs. After comparing initial MRI (MRI-1) and MRI-2, an observer, blinded to the dog's clinical signs, described the MRI-2 findings. The study population was then divided into symptomatic or asymptomatic at the time of MRI-2. Two separate observers subjectively classified the discospondylitis as active or inactive. Repeatability and interobserver agreement were evaluated. Results: A total of 25 dogs were included. At the time of MRI-2 16 (64%) dogs were asymptomatic and 9 (36%) were symptomatic. Based on MRI-2, 20 (80%) and 18 (72%) out of 25 dogs were considered to have active discospondylitis by the first and second observers, respectively. Interobserver agreement was moderate. No MRI-2 features were associated with the clinical status. The subjective classification of inactive discospondylitis was significantly associated with asymptomatic clinical status, but the classification of active discospondylitis was evenly distributed between groups. Conclusion: This study did not identify a meaningful association between the clinical status of dogs treated for presumptive discospondylitis and MRI-2 results. There were no specific MRI-2 features which were associated with the clinical status

Nonlinear diffusion & thermo-electric coupling in a two-variable model of cardiac action potential

This work reports the results of the theoretical investigation of nonlinear dynamics and spiral wave breakup in a generalized two-variable model of cardiac action potential accounting for thermo-electric coupling and diffusion nonlinearities. As customary in excitable media, the common Q10 and Moore factors are used to describe thermo-electric feedback in a 10-degrees range. Motivated by the porous nature of the cardiac tissue, in this study we also propose a nonlinear Fickian flux formulated by Taylor expanding the voltage dependent diffusion coefficient up to quadratic terms. A fine tuning of the diffusive parameters is performed a priori to match the conduction velocity of the equivalent cable model. The resulting combined effects are then studied by numerically simulating different stimulation protocols on a one-dimensional cable. Model features are compared in terms of action potential morphology, restitution curves, frequency spectra and spatio-temporal phase differences. Two-dimensional long-run simulations are finally performed to characterize spiral breakup during sustained fibrillation at different thermal states. Temperature and nonlinear diffusion effects are found to impact the repolarization phase of the action potential wave with non-monotone patterns and to increase the propensity of arrhythmogenesis

Quasinormal modes of Kerr-Newman black holes: coupling of electromagnetic and gravitational perturbations

We compute numerically the quasinormal modes of Kerr-Newman black holes in the scalar case, for which the perturbation equations are separable. Then we study different approximations to decouple electromagnetic and gravitational perturbations of the Kerr-Newman metric, computing the corresponding quasinormal modes. Our results suggest that the Teukolsky-like equation derived by Dudley and Finley gives a good approximation to the dynamics of a rotating charged black hole for Q<M/2. Though insufficient to deal with Kerr-Newman based models of elementary particles, the Dudley-Finley equation should be adequate for astrophysical applications.Comment: 13 pages, 3 figures. Minor changes to match version accepted in Phys. Rev.

Applicazioni di livello “0” della metodologia utilizzata per la valutazione del rischio sismico di Sistemi Urbani, utilizzando l’analogia delle reti neuronali

Questa ricerca, condotta nell’ambito del Progetto RELUIS – Linea 10, ha riguardato la messa a punto di un modello di rischio sismico per Sistemi Urbani con approccio multilivello, utilizzando l’analogia con le reti neuronali. Il primo passo è stata l’elaborazione del livello 0, basato su banche-dati, disponibili a livello nazionale, relative alla pericolosità sismica di base e locale (INGV) e a dati di censimento dei comuni italiani (ANCITEL 2001; ISTAT 2001) per la descrizione fisica e funzionale dei centri abitati/sistemi urbani analizzati. Per semplicità e per omogeneità tra i molti dati elaborati sono stati trascurati due aspetti rilevanti per il modello di rete neuronale, che intervengono invece ai livelli successivi, ovvero l’aspetto della “soglia” di perdita di capacità di una componente di sottosistema (sia per evoluzione che per connessione) e l’aspetto della “capacità iniziale” di una componente di sottosistema prima dell’evento sismico. La valutazione della perdita di capacità complessiva di un Sistema Urbano a livello 0 è stata quindi calcolata come l’insieme delle perdite di tutti i sistemi combinati tra loro (con opportuni pesi) e quindi con un valore complessivo

Trojan Horse as an indirect technique in nuclear astrophysics. Resonance reactions

The Trojan Horse method is a powerful indirect technique that provides information to determine astrophysical factors for binary rearrangement processes $x + A \to b + B$ at astrophysically relevant energies by measuring the cross section for the Trojan Horse reaction $a + A \to y+ b + B$ in quasi-free kinematics. We present the theory of the Trojan Horse method for resonant binary subreactions based on the half-off-energy-shell R matrix approach which takes into account the off-energy-shell effects and initial and final state interactions.Comment: 6 pages and 1 figur