Biology subjects

Pizzamiglio, L.

Publications and source records attributed to Pizzamiglio, L..

4 recordsLinked to original sources

bioRxiv2026

How artists experience their own art

Humanity has always admired and created artwork, but the neurocognitive mechanisms behind artistic experience are still elusive. Professional artists and their intimate relationship with their artworks provide a unique opportunity to study the nature of art experience due to their expertise in both art making and art appreciation. During two fMRI tasks, professional artists (N=20) made aesthetic judgments on their own and other artists paintings (aesthetic appreciation task); they also mentally reconstructed the moments when they conceived their artworks or, as a control condition, when they visited now-familiar places for the first time (reconstruction by imagery task). During art appreciation of their own (as compared to other artists) paintings, participants showed stronger recruitment of bilateral posterior parietal cortices, the left lateral occipitotemporal cortex, and the dorso-central sector of the right insula, that is, action-related brain regions also involved in encoding the emotional components of movements. The reconstruction of their own artistic creation (as compared to episodic memory retrieval) involved the left fronto-parietal network associated with motor cognition. Altogether, these results suggest that the mental representations of the actions involved in creating art are integral to the overall artistic experience of painters, supporting an embodied view of the artists experience of art.

neuroscience↗

bioRxiv2024

Neurodevelopmental defects in Dravet syndrome Scn1a+/- mice: selective rescue of behavioral alterations but not seizures by targeting GABA-switch.

Dravet syndrome (DS) is a developmental and epileptic encephalopathy (DEE) caused by mutations of the SCN1A gene (NaV1.1 sodium channel) and characterized by seizures, motor disabilities and cognitive/behavioral deficits, including autistic traits. The relative role of seizures and neurodevelopmental defects in disease progression, as well as the role of the mutation in inducing early neurodevelopmental defects before symptoms onset, are not clear yet. A delayed switch of GABAergic transmission from excitatory to inhibitory (GABA-switch) was reported in models of DS, but its effects on the phenotype have not been investigated. Using a multi-scale approach, here we show that targeting GABA-switch with the drugs KU55933 (KU) or bumetanide (which upregulate KCC2 or inhibits NKCC1 chloride transporters, respectively) rescues social interaction deficits and reduces hyperactivity observed in P21 Scn1a+/- DS mouse model. Bumetanide also improves spatial working memory defects. Importantly, neither KU nor bumetanide have effect on seizures or mortality rate. Also, we disclose early behavioral defects and delayed neurodevelopmental milestones well before seizure onset, at the beginning of NaV1.1 expression. We thus reveal that neurodevelopmental components in DS, in particular GABA switch, selectively underlie some cognitive/behavioral defects, but not seizures. Our work provides further evidence that seizures and neuropsychiatric dysfunctions in DEEs can be uncoupled and can have differential pathological mechanisms. They could be treated separately with targeted pharmacological strategies.

neuroscience↗

bioRxiv2024

Neural precursor cells rescue symptoms of Rett syndrome by activation of the Interferon γ pathway

The beneficial effects of Neural Precursor Cell (NPC) transplantation in several neurological disorders are well established and they are generally mediated by the secretion of immunomodulatory and neurotrophic molecules. We therefore investigated whether Rett syndrome (RTT), that represents the first cause of severe intellectual disability in girls, might benefit from an NPC-based therapy. Using in vitro co-cultures, we demonstrate that, by sensing the pathological context, NPC-secreted factors induce the recovery of morphological and synaptic defects typical of Mecp2 deficient neurons. In vivo, we prove that intracerebral transplantation of NPCs in RTT mice significantly ameliorates neurological functions. To uncover the molecular mechanisms underpinning the mediated benefic effects, we analysed the transcriptional profile of the cerebellum of transplanted animals, disclosing the possible involvement of the Interferon {gamma} (IFN{gamma}) pathway. Accordingly, we report the capacity of IFN{gamma} to rescue synaptic defects, as well as motor and cognitive alterations in Mecp2 deficient models, thereby suggesting this molecular pathway as a potential therapeutic target for RTT.

neuroscience↗

bioRxiv2019

CAP2 is a novel regulator of Cofilin in synaptic plasticity and Alzheimer’s disease

Cofilin is one of the major regulators of actin dynamics in spines where it is required for structural synaptic plasticity. However, our knowledge of the mechanisms controlling Cofilin activity in spines remains still fragmented. Here, we describe the cyclase-associated protein 2 (CAP2) as a novel master regulator of Cofilin localization in spines. The formation of CAP2 dimers through its Cys32 is important for CAP2 binding to Cofilin and for normal spine actin turnover. The Cys32-dependent CAP2 homodimerization and association to Cofilin are triggered by long-term potentiation (LTP) and are required for LTP-induced Cofilin translocation into spines, spine remodeling and the potentiation of synaptic transmission. This mechanism is specifically affected in the hippocampus, but not in the superior frontal gyrus, of both Alzheimers Disease (AD) patients and APP/PS1 mice, where CAP2 is down-regulated and CAP2 dimer synaptic levels are reduced. In AD hippocampi, Cofilin preferentially associates with CAP2 monomer and is aberrantly localized in spines. Taken together, these results provide novel insights into structural plasticity mechanisms that are defective in AD.

neuroscience↗