Italian Institute of Neuroscience

Sant'Ambrogio di Torino, Italy

Italian Institute of Neuroscience

Sant'Ambrogio di Torino, Italy
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Marini F.,University of Milan Bicocca | Chelazzi L.,University of Verona | Chelazzi L.,Italian Institute of Neuroscience | Maravita A.,University of Milan Bicocca
Journal of Experimental Psychology: General | Year: 2013

When dealing with significant sensory stimuli, performance can be hampered by distracting events. Attention mechanisms lessen such negative effects, enabling selection of relevant information while blocking potential distraction. Recent work shows that preparatory brain activity, occurring before a critical stimulus, may reflect mechanisms of attentional control aimed to filter upcoming distracters. However, it is unknown whether the engagement of these filtering mechanisms to counteract distraction in itself taxes cognitive-brain systems, leading to performance costs. Here we address this question and, specifically, seek the behavioral signature of a mechanism for the filtering of potential distraction within and between sensory modalities. We show that, in potentially distracting contexts, a filtering mechanism is engaged to cope with forthcoming distraction, causing a dramatic behavioral cost in no-distracter trials during a speeded tactile discrimination task. We thus demonstrate an impaired processing caused by a potential, yet absent, distracter. This effect generalizes across different sensory modalities, such as vision and audition, and across different manipulations of the context, such as the distracter's sensory modality and pertinence to the task. Moreover, activation of the filtering mechanism relies on both strategic and reactive processes, as shown by its dynamic dependence on probabilistic and cross-trial contingencies. Crucially, across participants, the observed strategic cost is inversely related to the interference exerted by a distracter on distracter-present trials. These results attest to a mechanism for the monitoring and filtering of potential distraction in the human brain. Although its activation is indisputably beneficial when distraction occurs, it leads to robust costs when distraction is actually expected but currently absent. © 2012 American Psychological Association.

Bigini P.,Mario Negri Institute for Pharmacological Research | Milanese M.,University of Milan | Gardoni F.,University of Milan | Longhi A.,University of Milan | And 7 more authors.
Journal of Neuroscience Research | Year: 2012

Neuronal ceroid lipofuscinoses (NCLs) are a group of hereditary childhood diseases characterized mainly by lipopigment accumulation and a multisystemic pattern of symptoms including mental retardation, seizures, motor impairment, and blindness. The mnd mouse, carrying a mutation in the Cln8 gene, has been proposed as a model of epilepsy with mental retardation (EPMR, ornorthern epilepsy). We recently showed neuronal hyperexcitability and seizure hypersusceptibility in mnd mice. To elucidate the cellular mechanisms related to hippocampal hyperexcitability, the glutamatergic transmission and the expression of postsynaptic glutamate receptors were investigated in hippocampus. A significant increase in either spontaneous or KCl-stimulated overflow of [ 3H]D-aspartate was found in mnd mice compared with controls. This increase was maintained after DL-threo-β-benzyloxyaspartic acid (TBOA) treatment, suggesting a nonrelevant role for transporter-mediated release and supporting the involvement of exocytotic [ 3H]D-aspartate release. Accordingly, Ca 2+-dependent overflow induced by ionomycin was also increased in mnd mice. Levels of glutamate 1-3 AMPA receptor subunits were increased, and levels of the NR2A NMDA receptor subunit were decreased in the hippocampus of mnd mice, suggesting an adaptive response to glutamate overstimulation. © 2012 Wiley Periodicals, Inc.

Marini F.,Duke University | Marini F.,University of Milan Bicocca | Marini F.,University of California at San Diego | Demeter E.,Duke University | And 4 more authors.
Journal of Neuroscience | Year: 2016

Giventhe information overload oftenimpartedtohumancognitive-processing systems, suppression of irrelevantanddistracting information is essential for successful behavior. Using a hybrid block/event-relatedfMRIdesign,wecharacterized proactiveandreactive brainmechanismsfor filtering distracting stimuli. Participants performed a flanker task, discriminating the direction of a target arrow in the presence versus absence of congruent or incongruent flanking distracting arrows during either Pure blocks (distracters always absent) or Mixed blocks (distracters on 80% of trials). Each Mixed block had either 20% or 60% incongruent trials. Activations in the dorsal frontoparietal attention network during Mixed versus Pure blocks evidenced proactive (blockwise) recruitment of a distraction-filtering mechanism. Sustained activations in right middle frontal gyrus during 60% Incongruent blocks correlated positively with behavioral indices of distraction-filtering (slowing when distractersmightoccur) and negatively with distraction-related behavioral costs(incongruent vs congruenttrials),suggesting a role in coordinating proactive filtering of potential distracters. Event-related analyses showed that incongruent trials elicited greater reactive activations in 20%(vs 60%) Incongruent blocks for counteracting distraction and conflict, including in the insula and anterior cingulate. Context-related effects in occipitoparietal cortex consisted of greater target-evoked activations for distracter-absent trials (central-target-only) in Mixed versus Pure blocks, suggesting enhanced attentional engagement. Functional-localizer analyses in V1/V2/V3 revealed less distracter-processing activity in 60% (vs 20%) Incongruent blocks, presumably reflecting tonic suppression by proactive filtering mechanisms. These results delineate brain mechanisms underlying proactive and reactive filtering of distraction and conflict, and how they are orchestrated depending on distraction probability, thereby aiding task performance. © 2016 the authors.

Chelazzi L.,University of Verona | Chelazzi L.,Italian Institute of Neuroscience | Estocinova J.,University of Verona | Estocinova J.,Pavol Jozef Safarik University | And 6 more authors.
Journal of Neuroscience | Year: 2014

Spatial priority maps are real-time representations of the behavioral salience of locations in the visual field, resulting from the combined influence of stimulus driven activity and top-down signals related to the current goals of the individual. They arbitrate which of a number of (potential) targets in the visual scene will win the competition for attentional resources. As a result, deployment of visual attention to a specific spatial location is determined by the current peak of activation (corresponding to the highest behavioral salience) across the map. Here we report a behavioral study performed on healthy human volunteers, where we demonstrate that spatial priority maps can be shaped via reward-based learning, reflecting long-lasting alterations (biases) in the behavioral salience of specific spatial locations. These biases exert an especially strong influence on performance under conditions where multiple potential targets compete for selection, conferring competitive advantage to targets presented in spatial locations associated with greater reward during learning relative to targets presented in locations associated with lesser reward. Such acquired biases of spatial attention are persistent, are nonstrategic in nature, and generalize across stimuli and task contexts. These results suggest that reward-based attentional learning can induce plastic changes in spatial priority maps, endowing these representations with the "intelligent" capacity to learn from experience. © 2014 the authors.

Chelazzi L.,University of Verona | Chelazzi L.,Italian Institute of Neuroscience | Della Libera C.,University of Verona | Della Libera C.,Italian Institute of Neuroscience | And 4 more authors.
Wiley Interdisciplinary Reviews: Cognitive Science | Year: 2011

Attentional modulation along the object-recognition pathway of the cortical visual system of primates has been shown to consist of enhanced representation of the retinal input at a specific location in space, or of objects located anywhere in the visual field which possess a critical object feature. Moreover, selective attention mechanisms allow the visual system to resolve competition among multiple objects in a crowded scene in favor of the object that is relevant for the current behavior. Finally, selective attention affects the spontaneous activity of neurons as well as their visually driven responses, and it does so not only by modulating the spiking activity of individual neurons, but also by modulating the degree of coherent firing within the critical neuronal populations. © 2010 John Wiley & Sons, Ltd.

Uccelli A.,University of Genoa | Uccelli A.,Advanced Biotechnology Center | Milanese M.,University of Genoa | Principato M.C.,University of Genoa | And 11 more authors.
Molecular Medicine | Year: 2012

Despite some advances in the understanding of amyotrophic lateral sclerosis (ALS) pathogenesis, significant achievements in treating this disease are still lacking. Mesenchymal stromal (stem) cells (MSCs) have been shown to be effective in several models of neurological disease. To determine the effects of the intravenous injection of MSCs in an ALS mouse model during the symptomatic stage of disease, MSCs (1 × 106) were intravenously injected in mice expressing human superoxide dismutase 1 (SOD1) carrying the G93A mutation (SOD1/G93A) presenting with experimental ALS. Survival, motor abilities, histology, oxidative stress markers and [3H]D-aspartate release in the spinal cord were investigated. MSC injection in SOD1/G93A mice improved survival and motor functions compared with saline-injected controls. Injected MSCs scantly home to the central nervous system and poorly engraft. We observed a reduced accumulation of ubiquitin agglomerates and of activated astrocytes and microglia in the spinal cord of MSC-treated SOD1/G93A mice, with no changes in the number of choline acetyltransferase- and glutamate transporter type 1-positive cells. MSC administration turned around the upregulation of metallothionein mRNA expression and of the activity of the antioxidant enzyme glutathione S-transferase, both associated with disease progression. Last, we observed that MSCs reverted both spontaneous and stimulus-evoked neuronal release of [3H]D-aspartate, a marker of endogenous glutamate, which is upregulated in SOD1/G93A mice. These findings suggest that intravenous administration of MSCs significantly improves the clinical outcome and pathological scores of mutant SOD1/G93A mice, thus providing the rationale for their exploitation for the treatment of ALS.

Condliffe S.B.,National Research Council Italy | Corradini I.,National Research Council Italy | Pozzi D.,National Research Council Italy | Pozzi D.,Italian Institute of Neuroscience | And 2 more authors.
Journal of Biological Chemistry | Year: 2010

In addition to its primary role as a fundamental component of the SNARE complex, SNAP-25 also modulates voltage-gated calcium channels (VGCCs) in various overexpression systems. Although these studies suggest a potential negative regulatory role of SNAP-25 on VGCC activity, the effects of endogenous SNAP-25 on native VGCC function in neurons are unclear. In the present study, we investigated the VGCC properties of cultured glutamatergic and GABAergic rat hippocampal neurons. Glutamatergic currents were dominated by P/Q-type channels, whereas GABAergic cells had a dominant L-type component. Also, glutamatergic VGCC current densities were significantly lower with enhanced inactivation rates and shifts in the voltage dependence of activation and inactivation curves compared with GABAergic cells. Silencing endogenous SNAP-25 in glutamatergic neurons did not alter P/Q-type channel expression or localization but led to increased VGCC current density without changes in the VGCC subtype proportions. Isolation of the P/Q-type component indicated that increased current in the absence of SNAP-25 was correlated with a large depolarizing shift in the voltage dependence of inactivation. Overexpressing SNAP-25 in GABAergic neurons reduced current density without affecting the VGCC subtype proportion. Accordingly, VGCC current densities in glutamatergic neurons from Snap-25+/- mice were significantly elevated compared with wild type glutamatergic neurons. Overall, this study demonstrates that endogenous SNAP-25 negatively regulates native VGCCs in glutamatergic neurons which could have important implications for neurological diseases associated with altered SNAP-25 expression. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

Hickey C.,VU University Amsterdam | Hickey C.,University of Trento | Chelazzi L.,University of Verona | Chelazzi L.,Italian Institute of Neuroscience | Theeuwes J.,VU University Amsterdam
PLoS ONE | Year: 2014

Existing visual search research has demonstrated that the receipt of reward will be beneficial for subsequent perceptual and attentional processing of features that have characterized targets, but detrimental for processing of features that have characterized irrelevant distractors. Here we report a similar effect of reward on location. Observers completed a visual search task in which they selected a target, ignored a salient distractor, and received random-magnitude reward for correct performance. Results show that when target selection garnered rewarding outcome attention is subsequently a.) primed to return to the target location, and b.) biased away from the location that was occupied by the salient, task-irrelevant distractor. These results suggest that in addition to priming features, reward acts to guide visual search by priming contextual locations of visual stimuli. © 2014 Hickey et al.

Caselli L.,University of Verona | Caselli L.,University of Parma | Chelazzi L.,University of Verona | Chelazzi L.,Italian Institute of Neuroscience
PLoS ONE | Year: 2011

The ability to swiftly and smoothly switch from one task set to another is central to intelligent behavior, because it allows an organism to flexibly adapt to ever changing environmental conditions and internal needs. For this reason, researchers interested in executive control processes have often relied on task-switching paradigms as powerful tools to uncover the underlying cognitive and brain architecture. In order to gather fundamental information at the single-cell level, it would be greatly helpful to demonstrate that non-human primates, especially the macaque monkey, share with us similar behavioral manifestations of task-switching and therefore, in all likelihood, similar underlying brain mechanisms. Unfortunately, prior attempts have provided negative results (e.g., Stoet & Snyder, 2003b), in that it was reported that macaques do not show the typical signature of task-switching operations at the behavioral level, represented by switch costs. If confirmed, this would indicate that the macaque cannot be used as a model approach to explore human executive control mechanisms by means of task-switching paradigms. We have therefore decided to re-explore this issue, by conducting a comparative experiment on a group of human participants and two macaque monkeys, whereby we measured and compared performance costs linked to task switching and resistance to interference across the two species. Contrary to what previously reported, we found that both species display robust task switching costs, thus supporting the claim that macaque monkeys provide an exquisitely suitable model to study the brain mechanisms responsible for maintaining and switching task sets. © 2011 Caselli, Chelazzi.

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