1,721,023 research outputs found
Time window in cholinomimetic ability to rescue long-term potentiation in neurodegenerating anti-nerve growth factor mice
No full textA deficit in cortical cholinergic synaptic transmission is a common feature of cognitive and behavioral impairment observed in neurodegenerative pathologies. AD11 transgenic mice producing blocking antibodies against Nerve Growth Factor (NGF) are characterized by a progressive neurodegenerative phenotype defined by the deposition of amyloid peptide, intracellular neurofibrillary tangles and by a marked cholinergic depletion. We exploited AD11 mice to develop a functional assay to investigate the impact of cholinergic deficit on cortical synaptic plasticity impairment at different neurodegenerative stages. In particular, we investigated the time course of long-term potentiation (LTP) impairment in neocortex of AD11 mice and potential rescue by acute pharmacological treatment with Acetylcholine (ACh) or the cholinergic agonist Galantamine (GAL). We showed that UP starts being absent in AD11 mice at 2 months, air age corresponding to early neurodegenerative stage characterized by the first observed decrease in number of basal forebrain cholinergic neurons (BFCNs) without overt cortical neurodegeneration. We demonstrated that acute ACh or GAL treatment fully reverts LTP impairment in 2 month old AD11 mice. In contrast, cholinergic treatment failed to recover synaptic plasticity deficit in aged (9-10 months) AD11 mice characterized by a severe cortical neurodegeneration
Visual Acuity Is Reduced in Alpha 7 Nicotinic Receptor Knockout Mice
No full textPURPOSE. Nicotinic receptors (nAChRs) are part of a heterogeneous family of pentameric ligand-gated ion channels that are widely expressed in the visual system. The impact of alpha 7 homomeric nAChRs on visual function was investigated using mutant mice lacking the alpha 7 nicotinic receptor subunit. METHODS. The spatial resolution limit was measured in alpha 7 knockout (alpha 7 KO) and age-matched control mice using three independent methods: an operant behavioral visual task (Prusky maze), cortical visual evoked potentials (VEPs), and the pattern electroretinogram (PERG) evoked by alternating gratings of different spatial frequencies and contrasts. RESULTS. Visual acuity measured by means of the visual water maze task was significantly decreased in the alpha 7 KO mice and, concordantly, there was a reduction of the cortical spatial resolution limit measured by VEPs. However, the PERG was normal in alpha 7 KO mice, compared with control mice. The use of fluorescently tagged cholera toxin showed that projections from the retina segregate normally in alpha 7 KO mice and, in line with this, the visual cortical responses elicited by stimulating either eye were normally balanced in both visual cortices and showed no retinotopic anomalies. CONCLUSIONS. These findings indicate that the absence of the alpha 7 nicotinic subunit reduces visual acuity. Because the cortical output has an abnormal spatial resolution but retinal output is preserved, it can be concluded that the low visual acuity was due to a deficit specifically present in the visual cortex. (Invest Ophthalmol Vis Sci. 2012;53:1211-1218) DOI:10.1167/iovs.11-800
THE ROLE OF CHOLINERGIC SYSTEM IN NEURONAL PLASTICITY: FOCUS ON VISUAL CORTEX AND MUSCARINIC RECEPTORS
No full textThis review is focused on the basal forebrain (BFB) cholinergic system, cholinergic receptors and cholinoceptive target areas such as the neocortex, all of which are intimately involved in high cognitive functions and synaptic plasticity. The neurons of the BFB synthesize acetylcholine (ACh) whose action is mediated by two subclasses of receptors, namely nicotinic and muscarinic receptors. Using the visual system as a model, the aim here is to integrate and discuss the current knowledge on anatomy, ontogeny and function of the BFB cholinergic system. This signaling system represents the anatomo-functional basis of ACh action on neuronal network, neuronal plasticity and cognitive functions. Cholinergic system role on higher brain functions has received increasing attention since the first observation of A. Alzheimer (1907) reporting dramatic changes of the BFB cholinergic neuro-anatomy in one of the most devastating neUrodegenerative diseases of adult brain, i.e. Alzheirner's disease (AD). In addition to this observation, later work demonstrated its participation in deep re-arrangements of brain connectivity such as the regulation of neuronal plasticity during maturation of cortical sensory maps, in adult and aged brain
Impaired synaptic plasticity in the visual cortex of mice lacking α7-nicotinic receptor subunit
No full textThe primary visual cortex (V1) is the first step in visual information processing and its function may be modulated by acetylcholine through nicotinic receptors (nAChRs). Since our previous work demonstrated that visual acuity and cortical spatial resolution limit were significantly reduced in α7 knock-out (KO) mice in the absence of retinal alterations, we decided to characterize the contribution of homomeric α7 nicotinic receptors (α7nAChRs) to visual information processing at the cortical level. We evaluated long-term forms of synaptic plasticity in occipital slices containing V1 from α7 KO mice and in wild-type (WT) slices perfused with nAChRs selective blocking agents. In α7 KO mice slices, electrophysiological recordings demonstrated the absence of long-term potentiation (LTP) and long-term depression (LTD) in layer II/III after the stimulation of different intracortical pathways (layer IV or II/III). Furthermore, the acute and selective blockade of α7nAChRs in slices from WT mice with either α-bungarotoxin or methyllycaconitine did not alter the expression of LTP and LTD. Conversely, the perfusion with the unspecific nAChRs antagonist mecamylamine impaired LTP and LTD. Our results suggest the presence of impaired synaptic plasticity in the V1 of α7 KO mice and indicate a different contribution of nAChRs to visual cortex function
Visual Cortex Plasticity: A Complex Interplay of Genetic and Environmental Influences
Full text linkThe central nervous system architecture is highly dynamic and continuously modified by sensory experience through processes of neuronal plasticity. Plasticity is achieved by a complex interplay of environmental influences and physiological mechanisms that ultimately activate intracellular signal transduction pathways regulating gene expression. In addition to the remarkable variety of transcription factors and their combinatorial interaction at specific gene promoters, epigenetic mechanisms that regulate transcription have emerged as conserved processes by which the nervous system accomplishes the induction of plasticity. Experience-dependent changes of DNA methylation patterns and histone posttranslational modifications are, in fact, recruited as targets of plasticity-associated signal transduction mechanisms. Here, we shall concentrate on structural and functional consequences of early sensory deprivation in the visual system and discuss how intracellular signal transduction pathways associated with experience regulate changes of chromatin structure and gene expression patterns that underlie these plastic phenomena. Recent experimental evidence for mechanisms of cross-modal plasticity following congenital or acquired sensory deprivation both in human and animal models will be considered as well. We shall also review different experimental strategies that can be used to achieve the recovery of sensory functions after long-term deprivation in humans
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
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
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