The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 20, 2018
Metaplasticity is the regulation of synaptic plasticity based on the history of previous synaptic... more Metaplasticity is the regulation of synaptic plasticity based on the history of previous synaptic activation. This concept was formulated after observing that synaptic changes in the visual cortex are not fixed, but dynamic and dependent on the history of visual information flux. In visual cortical neurons, sustained synaptic stimulation activate the enzymatic complex NOX2, resulting in the generation of reactive oxygen species (ROS). NOX2 is the main molecular structure responsible for translating neural activity into redox modulation of intracellular signaling pathways involved in plastic changes. Here, we studied the interaction between NOX2 and visual experience as metaplastic factors regulating synaptic plasticity at the supergranular layers of the mouse visual cortex. We found that genetic inhibition of NOX2 reverses the polarizing effects of dark rearing from LTP to LTD. In addition, we demonstrate that this process relies on changes in the NMDA receptor functioning. Altogeth...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 17, 2014
Reactive oxygen species (ROS) are signaling factors involved in many intracellular transduction p... more Reactive oxygen species (ROS) are signaling factors involved in many intracellular transduction pathways. In the nervous system, ROS are thought to modulate various mechanisms of synaptic plasticity. One important source of ROS production in the brain is the NADPH oxidase complex. Stimulation of NMDA receptors activates NADPH oxidase, which provides selective oxidative responses accompanying the induction of synaptic changes. The activity of NADPH oxidase is known to be crucial for the induction of LTP in the hippocampus. However, the involvement of this complex in cortical synaptic plasticity is still unclear. Here we provide evidence that genetic ablation of NOX2 (the prototypical member of NADPH oxidase family of proteins) suppresses LTP and LTD in the primary visual cortex of the mouse. We also found that the involvement of NOX2 on LTP is partially age-dependent, as the activity of this complex is not critical for mechanisms of synaptic potentiation occurring in immature animals...
Increasing evidence suggests that plastic changes underlying skill learning may occur at early st... more Increasing evidence suggests that plastic changes underlying skill learning may occur at early stages of neural processing. However, whether visual perceptual learning (PL) is accompanied by neuronal plasticity phenomena in the primary visual cortex (V1) is yet unknown. Here, we provide the first evidence that practice with specific visual stimuli (gratings) induces long-term potentiation (LTP) of synaptic responses in the rat V1. We report that in rats which have improved through practice their ability to discriminate between two gratings of different spatial frequency, the input/output curves of field potentials evoked in layers II-III of V1 slices by stimulation of either vertical and horizontal connections are shifted leftward compared to controls. Thus, visual PL is followed by potentiation of synaptic transmission both in vertical and horizontal connections (mimicry). We next show that this increase in intracortical connectivity gain is paralleled by LTP-like phenomena caused by the learning process: indeed, visual PL occludes further LTP (occlusion). Mimicry and occlusion are not present in the primary somatosensory cortex of rats trained with PL. These results demonstrate that LTP accompanies PL and highlight the notion that learning can occur at processing stages as early as the primary sensory cortices.
ERK 1,2 pathway mediates experience-dependent gene transcription in neurons and several studies h... more ERK 1,2 pathway mediates experience-dependent gene transcription in neurons and several studies have identified its pivotal role in experience-dependent synaptic plasticity and in forms of long term memory involving hippocampus, amygdala, or striatum. The perirhinal cortex (PRHC) plays an essential role in familiarity-based object recognition memory. It is still unknown whether ERK activation in PRHC is necessary for recognition memory consolidation. Most important, it is unknown whether by modulating the gain of the ERK pathway it is possible to bidirectionally affect visual recognition memory and PRHC synaptic plasticity. We have first pharmacologically blocked ERK activation in the PRHC of adult mice and found that this was sufficient to impair long term recognition memory in a familiarity-based task, the object recognition task (ORT). We have then tested performance in the ORT in Ras-GRF1 knock-out (KO) mice, which exhibit a reduced activation of ERK by neuronal activity, and in ERK1 KO mice, which have an increased activation of ERK2 and exhibit enhanced striatal plasticity and striatal mediated memory. We found that Ras-GRF1 KO mice have normal short term memory but display a long term memory deficit; memory reconsolidation is also impaired. On the contrary, ERK1 KO mice exhibit a better performance than WT mice at 72h retention interval, suggesting a longer lasting recognition memory. In parallel with behavioral data, LTD was strongly reduced and LTP was significantly smaller in PRHC slices from Ras-GRF1 KO than in WT mice while enhanced LTP and LTD were found in PRHC slices from ERK1 KO mice.
Increasing evidence suggests that plastic changes underlying skill learning may occur at early st... more Increasing evidence suggests that plastic changes underlying skill learning may occur at early stages of neural processing. However, whether visual perceptual learning (PL) is accompanied by neuronal plasticity phenomena in the primary visual cortex (V1) is yet unknown. Here, ...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 20, 2018
Metaplasticity is the regulation of synaptic plasticity based on the history of previous synaptic... more Metaplasticity is the regulation of synaptic plasticity based on the history of previous synaptic activation. This concept was formulated after observing that synaptic changes in the visual cortex are not fixed, but dynamic and dependent on the history of visual information flux. In visual cortical neurons, sustained synaptic stimulation activate the enzymatic complex NOX2, resulting in the generation of reactive oxygen species (ROS). NOX2 is the main molecular structure responsible for translating neural activity into redox modulation of intracellular signaling pathways involved in plastic changes. Here, we studied the interaction between NOX2 and visual experience as metaplastic factors regulating synaptic plasticity at the supergranular layers of the mouse visual cortex. We found that genetic inhibition of NOX2 reverses the polarizing effects of dark rearing from LTP to LTD. In addition, we demonstrate that this process relies on changes in the NMDA receptor functioning. Altogeth...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 17, 2014
Reactive oxygen species (ROS) are signaling factors involved in many intracellular transduction p... more Reactive oxygen species (ROS) are signaling factors involved in many intracellular transduction pathways. In the nervous system, ROS are thought to modulate various mechanisms of synaptic plasticity. One important source of ROS production in the brain is the NADPH oxidase complex. Stimulation of NMDA receptors activates NADPH oxidase, which provides selective oxidative responses accompanying the induction of synaptic changes. The activity of NADPH oxidase is known to be crucial for the induction of LTP in the hippocampus. However, the involvement of this complex in cortical synaptic plasticity is still unclear. Here we provide evidence that genetic ablation of NOX2 (the prototypical member of NADPH oxidase family of proteins) suppresses LTP and LTD in the primary visual cortex of the mouse. We also found that the involvement of NOX2 on LTP is partially age-dependent, as the activity of this complex is not critical for mechanisms of synaptic potentiation occurring in immature animals...
Increasing evidence suggests that plastic changes underlying skill learning may occur at early st... more Increasing evidence suggests that plastic changes underlying skill learning may occur at early stages of neural processing. However, whether visual perceptual learning (PL) is accompanied by neuronal plasticity phenomena in the primary visual cortex (V1) is yet unknown. Here, we provide the first evidence that practice with specific visual stimuli (gratings) induces long-term potentiation (LTP) of synaptic responses in the rat V1. We report that in rats which have improved through practice their ability to discriminate between two gratings of different spatial frequency, the input/output curves of field potentials evoked in layers II-III of V1 slices by stimulation of either vertical and horizontal connections are shifted leftward compared to controls. Thus, visual PL is followed by potentiation of synaptic transmission both in vertical and horizontal connections (mimicry). We next show that this increase in intracortical connectivity gain is paralleled by LTP-like phenomena caused by the learning process: indeed, visual PL occludes further LTP (occlusion). Mimicry and occlusion are not present in the primary somatosensory cortex of rats trained with PL. These results demonstrate that LTP accompanies PL and highlight the notion that learning can occur at processing stages as early as the primary sensory cortices.
ERK 1,2 pathway mediates experience-dependent gene transcription in neurons and several studies h... more ERK 1,2 pathway mediates experience-dependent gene transcription in neurons and several studies have identified its pivotal role in experience-dependent synaptic plasticity and in forms of long term memory involving hippocampus, amygdala, or striatum. The perirhinal cortex (PRHC) plays an essential role in familiarity-based object recognition memory. It is still unknown whether ERK activation in PRHC is necessary for recognition memory consolidation. Most important, it is unknown whether by modulating the gain of the ERK pathway it is possible to bidirectionally affect visual recognition memory and PRHC synaptic plasticity. We have first pharmacologically blocked ERK activation in the PRHC of adult mice and found that this was sufficient to impair long term recognition memory in a familiarity-based task, the object recognition task (ORT). We have then tested performance in the ORT in Ras-GRF1 knock-out (KO) mice, which exhibit a reduced activation of ERK by neuronal activity, and in ERK1 KO mice, which have an increased activation of ERK2 and exhibit enhanced striatal plasticity and striatal mediated memory. We found that Ras-GRF1 KO mice have normal short term memory but display a long term memory deficit; memory reconsolidation is also impaired. On the contrary, ERK1 KO mice exhibit a better performance than WT mice at 72h retention interval, suggesting a longer lasting recognition memory. In parallel with behavioral data, LTD was strongly reduced and LTP was significantly smaller in PRHC slices from Ras-GRF1 KO than in WT mice while enhanced LTP and LTD were found in PRHC slices from ERK1 KO mice.
Increasing evidence suggests that plastic changes underlying skill learning may occur at early st... more Increasing evidence suggests that plastic changes underlying skill learning may occur at early stages of neural processing. However, whether visual perceptual learning (PL) is accompanied by neuronal plasticity phenomena in the primary visual cortex (V1) is yet unknown. Here, ...
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Papers by Roberto De Pasquale