1,720,959 research outputs found
Synaptic and Extrasynaptic Origin of the Excitation/Inhibition Imbalance in the Hippocampus of Synapsin I/II/III Knockout Mice.
No full textSynapsins (Syn I, Syn II, and Syn III) are a family of synaptic vesicle phosphoproteins regulating synaptic transmission and plasticity. SYN1/2 genes have been identified as major epilepsy susceptibility genes in humans and synapsin I/II/III triple knockout (TKO) mice are epileptic. However, excitatory and inhibitory synaptic transmission and short-term plasticity have never been analyzed in intact neuronal circuits of TKO mice. To clarify the generation and expression of the epileptic phenotype, we performed patch-clamp recordings in the CA1 region of acute hippocampal slices from 1-month-old presymptomatic and 6-month-old epileptic TKO mice and age-matched controls. We found a strong imbalance between basal glutamatergic and gamma-aminobutyric acid (GABA) ergic transmission with increased evoked excitatory postsynaptic current and impaired evoked inhibitory postsynaptic current amplitude. This imbalance was accompanied by a parallel derangement of short-term plasticity paradigms, with enhanced facilitation of glutamatergic transmission in the presymptomatic phase and milder depression of inhibitory synapses in the symptomatic phase. Interestingly, a lower tonic GABA(A) current due to the impaired GABA release is responsible for the more depolarized resting potential found in TKO CA1 neurons, which makes them more susceptible to fire. All these changes preceded the appearance of epilepsy, indicating that the distinct changes in excitatory and inhibitory transmission due to the absence of Syns initiate the epileptogenic process
Cortico-hippocampal hyperexcitability in synapsin I/II/III knockout mice: age-dependency and response to the antiepileptic drug levetiracetam.
No full textSynapsins (SynI, SynII, SynIII) are a multigene family of synaptic vesicle phosphoproteins implicated in the regulation of synaptic transmission and plasticity. Synapsin I, II, I/II and I/II/III knockout mice are epileptic and SYN1/2 genes have been identified as major epilepsy susceptibility genes in humans. We analyzed cortico-hippocampal hyperexcitability and epileptiform activity induced by 4-aminopyridine (4AP) in acute slices from presymptomatic (3-weeks-old) and epileptic (1-year-old) SynI/II/III triple knockout (TKO) mice and aged-matched triple wild type (TWT) controls and assessed the effect of the synaptic vesicle-targeted antiepileptic drug levetiracetam (LEV) in reverting the epileptic phenotype.
Both fast and slow interictal (I-IC) activity and ictal (IC) seizures were observed in both genotypes. The incidence of fast I-IC was higher in presymptomatic TKO slices, while frequency and latency of I-IC events were similar in both genotypes. The major age and genotype effects were observed in IC activity, that was much more pronounced in 3-weeks-old TKO and persisted with age, while it disappeared from 1-year-old TWT slices. LEV virtually suppressed fast I-IC and IC discharges from 3-weeks-old TWT slices, while it only ameliorated fast I-IC and IC activity in TKO slices.
Analysis of I-IC events in patch-clamped CA1 pyramidal neurons revealed that LEV increased the inhibitory/excitatory ratio of I-IC activity in both genotypes. The lower LEV potency in TKO slices of both ages was associated with a decreased expression of SV2A, a synaptic vesicle protein acting as LEV receptor, in cortex and hippocampus. The results demonstrate that deletion of synapsin genes is associated with a higher propensity to 4AP-induced epileptic paroxysms that precedes the onset of epilepsy and consolidates with age. LEV ameliorates such hyperexcitability by enhancing the inhibition/excitation ratio, although the effect is hindered in TKO slices due to the concomitant decrease of its receptor SV2A
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Cortico-hippocampal hyperexcitability in synapsin I/II/III knockout mice: age-dependency and response to the antiepileptic drug levetiracetam
No full textSynapsins (Synl, SynII, SynIII) are a multigene family of synaptic vesicle (SV) phosphoproteins implicated in the regulation of synaptic transmission and plasticity. Synapsin I, II, I/II and I/II/III knockout mice are epileptic and SYN1/2 genes have been identified as major epilepsy susceptibility genes in humans. We analyzed cortico-hippocampal epileptiform activity induced by 4-aminopyridine (4AP) in acute slices from presymptomatic (3-weeks-old) and symptomatic (1-year-old) Syn I/II/III triple knockout (TKO) mice and aged-matched triple wild type (TWT) controls and assessed the effect of the SV-targeted antiepileptic drug (AED) levetiracetam (LEV) in reverting the epileptic phenotype. Both fast and slow interictal (I-IC) and ictal (IC) events were observed in both genotypes. The incidence of fast I-IC events was higher in presymptomatic TKO slices, while frequency and latency of I-IC events were similar in both genotypes. The major age and genotype effects were observed in IC activity, that was much more pronounced in 3-weeks-old TKO and persisted with age, while it disappeared from 1-year-old TWT slices. LEV virtually suppressed fast I-IC and IC discharges from 3-weeks-old TINT slices, while it only increased the latency of fast I-IC and IC activity in TKO slices. Analysis of I-IC events in patch-clamped CA1 pyramidal neurons revealed that LEV increased the inhibitory/excitatory ratio of I-IC activity in both genotypes. The lower LEV potency in TKO slices of both ages was associated with a decreased expression of SV2A, a SV protein acting as LEV receptor, in cortex and hippocampus. The results demonstrate that deletion of Syn genes is associated with a higher propensity to 4AP-induced epileptic paroxysms that precedes the onset of epilepsy and consolidates with age. LEV ameliorates such hyper excitability by enhancing the inhibition/excitation ratio, although the effect is hindered in TKO slices which exhibit a concomitant decrease in the levels of the LEV receptor SV2A. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Stress at the synapse: the synaptic action of acute behavioural stress and the protective effect of psychiatric drugs
No full textPurpose of the study: Recent neuroimaging and
histopathological studies on psychiatric patients have
shown morphometrical and functional modifications in
brain areas with glutamate predominance. There are many
evidences that repeated exposure to different stressful
events represents a risk factor for neuropsychiatric
diseases. Preclinical studies showed that the exposure of
rodents to stress produces many concomitans observed
in human pathology. Indeed, in rats stress induces
morphometrical alterations in brain areas probably due
to neuronal atrophy and associated with hyperactivation
of excitatory amino acid transmission [1].
Aim of this work was to study the effect of acute stress
on glutamate release, to analyze the mechanisms whereby
stress modifies glutamate release and to understand if these
changes are dampened by chronic antidepressants.
Methods: Rats were chronically (2 weeks) treated with
vehicle or drugs employed for therapy of mood/anxiety
disorders and then subjected to a standard Footshock
(FS)-stress protocol [2]. Immediately after FS-stress,
prefrontal/frontal cortex (P/FC) was dissected and synaptosomes
were purified on Percoll gradients; glutamate release
was measured [3]. SNARE complexes were measured in
un-boiled samples of synaptic membranes by SDS-PAGE
and Western blot. Electrophysiological experiments were
performed on acute P/FC slices [3]. Changes in vesicles
mobilization were measured by Total Internal Reflection
Fluorescence Microscopy (TIRFM).
Results: Acute FS-stress induced a marked increase
of circulating corticosterone (CORT) in all stressed rats
(vehicle- and antidepressant (AD)-treated) and a rapid (non
genomic) increase of glutamate release from synaptosomes
of P/FC via selective activation of glucocorticoid receptor.
The increase of glutamate release was prevented by chronic
AD treatments [3]. On the molecular level, FS-stress
induced a rapid accumulation of SNARE complexes in
presynaptic membranes of rats pre-treated or not with
ADs. Patch-clamp recordings on P/FC pyramidal neurons
revealed that FS-stress induced changes in paired-pulse
facilitation (PPF) and its Ca2+-dependence, consistent with
an increase in glutamate release. Chronic desipramine
(DMI) completely prevented this effect [3].
Because the number of SNARE complexes per vesicle
is fixed, the accumulation induced by stress suggests
that FS-stress may increase the size of the readily
releasable pool (RRP) of vesicles (docked vesicles).
Therefore we measured the release of glutamate from
P/FC synaptosomes of control and FS-stressed rats evoked
by sucrose (250–500 mM), which mobilizes the RRP. In
line with SNARE complex accumulation, RRP size was
markedly increased in P/FC synaptosomes from stressed
rats (vehicle and ADs-treated).
Furthermore, we investigated the effects of stress on
synaptic vesicle kinetics with TIRFM. Since the effects
of CORT on glutamate release and SNARE complex
accumulation seem to be non genomic, we incubated
synaptosomes in vitro with CORT and we visualized
with TIRFM the changes induced by CORT and in vitro
depolarization on vesicle mobilization.
Conclusions: Overall, the combined results of this study
give more insight into the basic mechanisms whereby
behavioural stress affects excitatory transmission in the
forebrain and show a novel effect of ADs that could be
related to their therapeutic action
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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