Extracellular α-synuclein (α-syn) assemblies can be up-taken by neurons; however, their interacti... more Extracellular α-synuclein (α-syn) assemblies can be up-taken by neurons; however, their interaction with the plasma membrane and proteins has not been studied specifically. Here we demonstrate that α-syn assemblies form clusters within the plasma membrane of neurons. Using a proteomic-based approach, we identify the α3-subunit of Na(+)/K(+)-ATPase (NKA) as a cell surface partner of α-syn assemblies. The interaction strength depended on the state of α-syn, fibrils being the strongest, oligomers weak, and monomers none. Mutations within the neuron-specific α3-subunit are linked to rapid-onset dystonia Parkinsonism (RDP) and alternating hemiplegia of childhood (AHC). We show that freely diffusing α3-NKA are trapped within α-syn clusters resulting in α3-NKA redistribution and formation of larger nanoclusters. This creates regions within the plasma membrane with reduced local densities of α3-NKA, thereby decreasing the efficiency of Na(+) extrusion following stimulus. Thus, interactions ...
Sensorimotor integration is crucial to perception and motor control. How and where this process t... more Sensorimotor integration is crucial to perception and motor control. How and where this process takes place in the brain is still largely unknown. Here we analyze the cerebellar contribution to sensorimotor integration in the whisker system of mice. We identify an area in the cerebellum where cortical sensory and motor inputs converge at the cellular level. Optogenetic stimulation of this area affects thalamic and motor cortex activity, alters parameters of ongoing movements and thereby modifies qualitatively and quantitatively touch events against surrounding objects. These results shed light on the cerebellum as an active component of sensorimotor circuits and show the importance of sensorimotor cortico-cerebellar loops in the fine control of voluntary movements.
Per plasticità si intendono tutte quelle modifiche anatomiche e fisiologiche a cui un circuito ne... more Per plasticità si intendono tutte quelle modifiche anatomiche e fisiologiche a cui un circuito neuronale va incontro a seguito di esperienza. All'interno dello sviluppo di un organismo esiste una finestra temporale, chiamata periodo critico, in cui l'attività sensoriale può ...
Down syndrome (DS) is the most common genetic disorder associated with mental retardation. It has... more Down syndrome (DS) is the most common genetic disorder associated with mental retardation. It has been repeatedly shown that Ts65Dn mice, the prime animal model for DS, have severe cognitive and neural plasticity defects due to excessive inhibition. We report that increasing sensory-motor stimulation in adulthood through environmental enrichment (EE) reduces brain inhibition levels and promotes recovery of spatial memory abilities, hippocampal synaptic plasticity, and visual functions in adult Ts65Dn mice.
... density, and postsynaptic thickening, that are particularly evident in the occipital cortex a... more ... density, and postsynaptic thickening, that are particularly evident in the occipital cortex and in the hip-pocampus (Mohammed et al ... of the Brain 17 Figure 2.6 Example of a chondroitin-sulfate proteoglycan perineuronal net immunostained for Wisteria floribunda (WFA) in the rat ...
While cortical circuits display maximal sensitivity to sensory experience during critical periods... more While cortical circuits display maximal sensitivity to sensory experience during critical periods of early postnatal development, far less plasticity is present in the mature brain. Ocular dominance shift of visual cortical neurons in response to eye occlusion and recovery of visual functions from a period of sensory deprivation are two classical models in the study of critical period determinants in the visual cortex. Recent papers employing various pharmacological and environmental strategies have shown that it is possible to reinstate much greater levels of plasticity in the adult visual cortex than previously suspected. These studies point toward intracortical inhibition as a crucial determinant for critical period regulation in the visual system and have a great potential for therapeutic rehabilitation and recovery from injury in the adult brain.
Extracellular α-synuclein (α-syn) assemblies can be up-taken by neurons; however, their interacti... more Extracellular α-synuclein (α-syn) assemblies can be up-taken by neurons; however, their interaction with the plasma membrane and proteins has not been studied specifically. Here we demonstrate that α-syn assemblies form clusters within the plasma membrane of neurons. Using a proteomic-based approach, we identify the α3-subunit of Na(+)/K(+)-ATPase (NKA) as a cell surface partner of α-syn assemblies. The interaction strength depended on the state of α-syn, fibrils being the strongest, oligomers weak, and monomers none. Mutations within the neuron-specific α3-subunit are linked to rapid-onset dystonia Parkinsonism (RDP) and alternating hemiplegia of childhood (AHC). We show that freely diffusing α3-NKA are trapped within α-syn clusters resulting in α3-NKA redistribution and formation of larger nanoclusters. This creates regions within the plasma membrane with reduced local densities of α3-NKA, thereby decreasing the efficiency of Na(+) extrusion following stimulus. Thus, interactions ...
Sensorimotor integration is crucial to perception and motor control. How and where this process t... more Sensorimotor integration is crucial to perception and motor control. How and where this process takes place in the brain is still largely unknown. Here we analyze the cerebellar contribution to sensorimotor integration in the whisker system of mice. We identify an area in the cerebellum where cortical sensory and motor inputs converge at the cellular level. Optogenetic stimulation of this area affects thalamic and motor cortex activity, alters parameters of ongoing movements and thereby modifies qualitatively and quantitatively touch events against surrounding objects. These results shed light on the cerebellum as an active component of sensorimotor circuits and show the importance of sensorimotor cortico-cerebellar loops in the fine control of voluntary movements.
Per plasticità si intendono tutte quelle modifiche anatomiche e fisiologiche a cui un circuito ne... more Per plasticità si intendono tutte quelle modifiche anatomiche e fisiologiche a cui un circuito neuronale va incontro a seguito di esperienza. All'interno dello sviluppo di un organismo esiste una finestra temporale, chiamata periodo critico, in cui l'attività sensoriale può ...
Down syndrome (DS) is the most common genetic disorder associated with mental retardation. It has... more Down syndrome (DS) is the most common genetic disorder associated with mental retardation. It has been repeatedly shown that Ts65Dn mice, the prime animal model for DS, have severe cognitive and neural plasticity defects due to excessive inhibition. We report that increasing sensory-motor stimulation in adulthood through environmental enrichment (EE) reduces brain inhibition levels and promotes recovery of spatial memory abilities, hippocampal synaptic plasticity, and visual functions in adult Ts65Dn mice.
... density, and postsynaptic thickening, that are particularly evident in the occipital cortex a... more ... density, and postsynaptic thickening, that are particularly evident in the occipital cortex and in the hip-pocampus (Mohammed et al ... of the Brain 17 Figure 2.6 Example of a chondroitin-sulfate proteoglycan perineuronal net immunostained for Wisteria floribunda (WFA) in the rat ...
While cortical circuits display maximal sensitivity to sensory experience during critical periods... more While cortical circuits display maximal sensitivity to sensory experience during critical periods of early postnatal development, far less plasticity is present in the mature brain. Ocular dominance shift of visual cortical neurons in response to eye occlusion and recovery of visual functions from a period of sensory deprivation are two classical models in the study of critical period determinants in the visual cortex. Recent papers employing various pharmacological and environmental strategies have shown that it is possible to reinstate much greater levels of plasticity in the adult visual cortex than previously suspected. These studies point toward intracortical inhibition as a crucial determinant for critical period regulation in the visual system and have a great potential for therapeutic rehabilitation and recovery from injury in the adult brain.
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Papers by Maria Spolidoro