123 research outputs found
Structural plasticity of climbing fibers and the growth-associated protein GAP-43
No full textStructural plasticity occurs physiologically or after brain damage to adapt or re-establish proper synaptic connections. This capacity depends on several intrinsic and extrinsic determinants that differ between neuron types. We reviewed the significant endogenous regenerative potential of the neurons of the inferior olive in the adult rodent brain and the structural remodeling of the terminal arbor of their axons the climbing fiber under various experimental conditions, focusing on the growth-associated protein GAP-43. Climbing fibers undergo remarkable collateral sprouting in the presence of denervated Purkinje cells that are available for new innervation. In addition, severed olivo-cerebellar axons regenerate across the white matter through a graft of embryonic Schwann cells. In contrast, climbing fibers undergo a regressive modification when their target is deleted. In vivo knockdown of GAP-43 in olivary neurons, leads to the atrophy of their climbing fibers and a reduction in the ability to sprout toward surrounding denervated Purkinje cells. These findings demonstrate that GAP-43 is essential for promoting denervation-induced sprouting and maintaining normal climbing fiber architecture
Manières d’être humain. Une autre philosophie morale
No full textPhilosophical ethics has been dominated for a long time by views (such as Utilitarianism and Kantianism) which aim at establishing normative criteria in isolation from concrete situations to which they are supposed to be applied. This book reverses the perspective and shifts the attention to the circumstances which make individual and social problems humanly and morally salient.
The task of ethics consists in deepening and reorganizing the ways of seeing, feeling, responding to the world which define the conceptual dimensions of our lives. The author elaborates on a tradition which begins with Wittgenstein and converses with Stanley Cavell, Elisabeth Anscombe, Iris Murdoch and Cora Diamond. It wishes to forge new philosophical instruments which allow to treat in a new way the issues of birth, death, sexuality and the conceptions of the human.Les conceptions philosophiques qui ont longtemps dominé l’éthique contemporaine (comme par exemple l’utilitarisme et le kantisme) visent à établir les critères normatifs en les isolant des situations concrètes auxquelles ils devaient être appliqués. Ce livre renverse une telle perspective et met au centre de sa réflexion les circonstances qui rendent humainement et moralement significatifs les problèmes dont se soucient les individus et les sociétés.
La tâche de l’éthique consiste alors en l’approfondissement et la réorganisation des manières de voir, de sentir, de réagir au monde qui définissent les dimensions conceptuelles de nos vies. Piergiorgio Donatelli réélabore une tradition qui part de Wittgenstein et dialogue avec des auteurs tels que Stanley Cavell, Elizabeth Anscombe, Iris Murdoch et Cora Diamond, en faisant émerger des nouveaux outils philosophiques qui permettent de traiter de façon nouvelle les questions concernant, par exemple, la naissance, la mort, la sexualité et les conceptions de l’humain
Embryonic Purkinje cells grafted on the surface of the cerebellar cortex integrate in the adult unlesioned cerebellum
No full textThe presence of an injury or the selective degeneration of specific neuronal populations is commonly assumed to be a necessary prerequisite for the survival and the integration of grafted neurons in the recipient brain. In the present study we have placed solid grafts of cerebellar anlage in the fourth ventricle of adult rats, in close contact with the host cerebellar cortex, to assess the capacity of embryonic Purkinje cells to interact with adult neurons and integrate in the unlesioned cerebellar cortex. Numerous grafted Purkinje cells are indeed able to leave the implant and migrate into the host molecular layer, where they develop adult structural features. In addition, such cells are able to elicit the growth of host climbing fibre sprouts which end in newly formed arborizations impinging upon their dendritic trees. Climbing fibre collateral branches also penetrate the implant to innervate Purkinje cells which have not migrated in the host cerebellum. These results show that embryonic Purkinje cells are able to survive and integrate in an adult unlesioned cerebellar cortex. In addition, adult olivary axons respond to the increased size of the target population by expanding their terminal domain to innervate grafted Purkinje cells
Exposure to kainic acid mimics the effects of axotomy in cerebellar Purkinje cells of the adult rat
No full textWe have investigated the long-term structural changes which affect Purkinje cells exposed to a single dose of kainic acid. Following intraparenchymal injection of the excitotoxin in the cerebellar cortex (1 microliter of a 1 mg/ml solution), Purkinje cells which survived within the lesioned area or close to its edges showed remarkable axonal abnormalities, involving the formation of torpedoes, hypertrophy of recurrent collaterals and atrophy of the corticofugal portion of the axon. In addition, their dendritic trees were often affected by conspicuous regressive alterations. The climbing fibres contacting these Purkinje cells were characterized by thick perisomatic plexuses, whereas their peridendritic branches were atrophic. The dendrites innervated by such atrophic olivary arbours were studded with huge numbers of newly formed spines. These alterations were already present a few days after kainic acid administration and persisted for the total period of observation of 6 months after the lesion. The remarkable similarity between the abnormalities of Purkinje cells exposed to kainic acid and those observed after axotomy indicates that in these two conditions common mechanisms determine analogous long-lasting modifications in the affected neurons. It is proposed that kainic acid-induced intracellular calcium overload disrupts cytoskeletal components and impairs axonal transport, thus depriving the affected Purkinje cells of retrograde trophic influences from their target neurons. As a consequence the affected neurons undergo long-lasting regressive modifications and compensatory remodelling phenomena
Impaired sprouting and axonal atrophy in cerebellar climbing fibres following in vivo silencing of the growth-associated protein GAP-43.
No full textThe adult mammalian central nervous system has a limited ability to establish new connections and to recover from traumatic or degenerative events. The olivo-cerebellar network represents an excellent model to investigate neuroprotection and repair in the brain during adulthood, due to its high plasticity and ordered synaptic organization. To shed light on the molecular mechanisms involved in these events, we focused on the growth-associated protein GAP-43 (also known as B-50 or neuromodulin). During development, this protein plays a crucial role in growth and in branch formation of neurites, while in the adult it is only expressed in a few brain regions, including the inferior olive (IO) where climbing fibres (CFs) originate. Following axotomy GAP-43 is usually up-regulated in association with regeneration. Here we describe an in vivo lentiviral-mediated gene silencing approach, used for the first time in the olivo-cerebellar system, to efficiently and specifically downregulate GAP-43 in rodents CFs. We show that lack of GAP-43 causes an atrophy of the CF in non-traumatic conditions, consisting in a decrease of its length, branching and number of synaptic boutons. We also investigated CF regenerative ability by inducing a subtotal lesion of the IO. Noteworthy, surviving CFs lacking GAP-43 were largely unable to sprout on surrounding Purkinje cells. Collectively, our results demonstrate that GAP-43 is essential both to maintain CFs structure in non-traumatic condition and to promote sprouting after partial lesion of the IO
Postsynaptic Current Mediated by Metabotropic Glutamate Receptors in Cerebellar Purkinje Cells
No full text Tempia, Filippo, Maria Concetta Miniaci, Davide Anchisi, and Piergiorgio Strata. Postsynaptic current mediated by metabotropic glutamate receptors in cerebellar Purkinje cells. J. Neurophysiol. 80: 520–528, 1998. In rat cerebellar slices, repetitive parallel fiber stimulation evokes an inward, postsynaptic current in Purkinje cells with a fast component mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors and a slower component mediated by metabotropic glutamate receptors (mGluR). The mGluR-mediated excitatory postsynaptic current (mGluR-EPSC) is evoked selectively by parallel fiber stimulation; climbing fiber stimulation is ineffective. The mGluR-EPSC is elicited most effectively with increasing frequencies of parallel fiber stimulation, from a threshold of 10 Hz to a maximum response at ∼100 Hz. The amplitude of the mGluR-EPSC is a linear function of the number of stimulus pulses without any apparent saturation, even with >10 pulses. Thus mGluRs at the parallel fiber-Purkinje cell synapse can function as linear detectors of the number of spikes in a burst of activity in parallel fibers. The mGluR-EPSC is present from postnatal day 15 and persists into adulthood. It is inhibited by the generic mGluR antagonist (RS)-a-methyl-4-carboxyphenylglycine and by the group I mGluR antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid at a concentration selective for mGluR1. Although the intracellular transduction pathway involves a G protein, the putative mediators of mGluR1 (phospholipase C and protein kinase C) are not directly involved, indicating that the mGluR-EPSC studied here is mediated by a different and still unidentified second-messenger pathway. Heparin, a nonselective antagonist of inositol-trisphosphate (IP3) receptors, has no significant effect on the mGluR-EPSC, suggesting that also IP3 might be not required for the response. Buffering intracellular Ca2+ with a high concentration of bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid partially inhibits the mGluR-EPSC, indicating that Ca2+ is not directly responsible for the response but that resting Ca2+ levels exert a tonic potentiating effect on the mGluR-EPSC. </jats:p
Alienation, appropriation, estrangement
No full textThe article discusses Rahel Jaeggi’s volume "Alienation". The author goes over crucial moments in the book and suggests a different way to tackle the issues treated from a Wittgensteinian perspective
La filosofia morale
No full textUna presentazione dei temi teorici principali dell'etica descritti nella prospettiva della filosofia analitica con una proposta sostantiva dell'autore.An introduction to the main theoretical issues in ethics described in the perspective of analytic philosophy with a substative proposal by the author
Le questioni etiche di fine vita in Italia nel 2020
No full textThe article surveys various issues around the debates on the end of life in Italy in the last decades. The author suggests that we are now in a new phase, and that we should say farewell to the Twentieth century and to its political culture
Murdoch e la permanenza della realtà
No full textL'articolo si concentra sull'uso della nozione di sfondo (background) nella filosofia di Iris Murdoch. Esso segnala il carattere duro e inesauribile della realtà, necessario per conferire significato alle attività umane. In secondo luogo, il carattere duro della realtà è oggetto di un lavoro morale di comprensione e di approfondimento al punto che tale durezza si trasforma in un fascio di relazioni che stabiliamo tra noi e gli aspetti di cui abbiamo guadagnato una comprensione morale. L'autore insiste sulla necessità di entrambe le prospettive, in particolare in relazione all'etica della vita umana, animale e ambientale.Iris Murdoch employs the notion of ‘background’, and notions related to it, in order to pursue various philosophic projects. The author explores Murdoch’s use of the notion in order to focus on two interconnected questions. On the one hand, the notion signals the hardness and inexhaustible character of reality, as the needed background in order to make sense of our lives in various ways. On the other, the hardness of reality is the object of a moral work of apprehension and deepening to the point at which its distinctive character dissolves into the family of connections we have gained for ourselves. The author elaborates on the necessity of both sides of the concept, especially in connection to the notion of life: human, animal, and environmental
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