1,720,985 research outputs found
Reduced inhibitory gate in the barrel cortex of Neuroligin3R451C knock-in mice, an animal model of autism spectrum disorders
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Functional role of ambient GABA in refining neuronal circuits early in postnatal development
No full textNanomedicine and graphene-based materials: advanced technologies for potential treatments of diseases in the developing nervous system
Full text linkAbstract: The interest in graphene-based nanomaterials (GBNs) application in nanomedicine, in particular in neurology, steadily increased in the last decades. GBNs peculiar physical–chemical properties allow the design of innovative therapeutic tools able to manipulate biological structures with subcellular resolution. In this review, we report GBNs applications to the central nervous system (CNS) when these nanomaterials are engineered as potential therapeutics to treat brain pathologies, with a focus on those of the pediatric age. We revise the state-of-the art studies addressing the impact of GBNs in the CNS, showing that the design of GBNs with different dimensions and chemical compositions or the use of specific administration routes and doses can limit unwanted side effects, exploiting GBNs efficacy in therapeutic approaches. These features favor the development of GBNs-based multifunctional devices that may find applications in the field of precision medicine for the treatment of disorders in the developing CNS. In this framework, we address the suitability of GBNs to become successful therapeutic tools, such as drug nano-delivery vectors when being chemically decorated with pharmaceutical agents and/or other molecules to obtain a high specific targeting of the diseased area and to achieve a controlled release of active molecules. Impact: The translational potential of graphene-based nanomaterials (GBNs) can be used for the design of novel therapeutic approaches to treat pathologies affecting the brain with a focus on the pediatric age.GBNs can be chemically decorated with pharmaceutical agents and molecules to obtain a highly specific targeting of the diseased site and a controlled drug release.The type of GBNs, the selected functionalization, the dose, and the way of administration are factors that should be considered to potentiate the therapeutic efficacy of GBNs, limiting possible side effects.GBNs-based multifunctional devices might find applications in the precision medicine and theranostics fields
In hippocampal oriens interneurons anti-Hebbian long-term potentiation requires cholinergic signaling via α7 nicotinic acetylcholine receptors
No full textIn hippocampal oriens interneurons anti-Hebbian Long-Term Potentiation requires cholinergic signalling via alpha 7 nicotinic acetylcholine receptors
No full textIn the hippocampus, at excitatory synapses between principal cell and oriens/alveus (O/A) interneurons, a particular form of NMDAindependent long-term synaptic plasticity (LTP) has been described (Lamsa et al., 2007). This type of LTP occurs when presynaptic activation coincides with postsynaptic hyperpolarization. For this reason it has been named "anti-Hebbian" to distinguish from the classical Hebbian type of associative learning where presynaptic glutamate release coincides with postsynaptic depolarization. The different voltage dependency of LTP induction is thought to be mediated by calcium-permeable (CP) AMPA receptors that, due to polyamine-mediated rectification, favor calcium entry at hyperpolarized potentials. Here, we report that the induction of this form of LTP needs CP-α7 nicotinic acetylcholine receptors (nAChRs) that, like CP-AMPARs, exhibit a strong inward rectification because of polyamine block at depolarizing potentials. We found that high-frequency stimulation of afferent fibers elicits synaptic currents mediated by α7 nAChRs. Hence, LTP was prevented by α7 nAChR antagonists dihydro-β-erythroidine and methyllycaconitine (MLA) and was absent in α7 -/- mice. In addition, in agreement with previous observations (Le Duigou and Kullmann, 2011), in a minority of O/A interneuronsin MLA-treated hippocampal slices from WT animals and α7 -/- mice, a form of LTP probably dependent on the activation of group I metabotropic glutamate receptors was observed. These data indicate that, in O/A interneurons, anti-Hebbian LTP critically depends on cholinergic signaling via α7 nAChR. This may influence network oscillations and information processing. © 2013 the authors
Functional role of ambient GABA in refining neuronal circuits early in postnatal development
Full text linkEarly in development, gamma-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-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 extrasynaptic5, 2, 3 and 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 GDPs which act as coincident detector signals to enhance synaptic efficacy at emerging GABAergic and glutamatergic synapses
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
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
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