Biology subjects

Cancedda, L.

Publications and source records attributed to Cancedda, L..

7 recordsLinked to original sources

bioRxiv2026

Endogenous oxytocin reconfigures brainwide network dynamics toward salience-related states

Oxytocin (OXT) can exert diverse effects across social, affective and motivational domains, yet its impact on brain function at the systems level remains unclear. Here, we combine chemogenetics with fMRI and electrophysiology in mice to investigate how endogenous OXT reshapes intrinsic large-scale brain network dynamics. Using mice constitutively expressing hM3Dq DREADD receptors in OXT-releasing hypothalamic neurons, we show that chemogenetic stimulation of OXT neurons elicits widespread increases in cerebral blood volume, with prominent effects in fronto-striatal regions and dorsal hippocampal areas. This broad functional response is accompanied by a network-specific reconfiguration of brain-wide functional connectivity, characterized by increased coupling between key components of the rodent social brain, and negative functional coupling between hippocampal and fronto-cortical regions. In vivo electrophysiology under matched conditions shows concordant changes in slow (<1 Hz) and delta-band coherence across frontalthalamic and fronto-hippocampal circuits, revealing a plausible neural correlate of the observed connectivity effects. Notably, these changes are accompanied by a marked reconfiguration of the temporal architecture of fMRI network activity, with increased occupancy of co-activation states engaging saliencerelated regions and a concomitant suppression of sensory-dominated states. Together, these findings identify dynamic network-state reconfiguration as a systems-level mechanism through which endogenous OXT can tune functional communication across social-affective circuits.

neuroscience↗

bioRxiv2025

Distinct spatial distribution of potentiated dendritic spines in encoding- and recall-activated hippocampal neurons

Experimental advancements in neuroscience have identified cellular engrams -- ensembles of neurons whose activation is necessary and sufficient for memory retrieval. Synaptic plasticity, including long-term potentiation, is key to memory encoding and recall, but the relationship between learning-induced dendritic spine potentiation and neuron-wide activation remains unclear. Here, we employ a post-synaptic translation-dependent potentiation reporter (SA-PSD{Delta}Venus) and a neuronal activation reporter (ESARE-dTurquoise) to determine their spatiotemporal correlation in the mouse hippocampal CA1 following contextual fear conditioning (CFC). Potentiated spines were enriched in activated neurons, with distribution varying across CA1 layers at different phases of memory: potentiated spines were more frequent in activated neurons in stratum oriens and stratum lacunosum moleculare after CFC (encoding), while recall-activated neurons showed a larger number of potentiated spines in the stratum radiatum. These findings demonstrate that the relative weight and spatial distribution of potentiated synaptic inputs to hippocampal CA1 pyramidal neurons changes between the encoding and retrieval phases of memory.

neuroscience↗

bioRxiv2025

Developmental excitation-inhibition imbalance permanently reprograms autism-relevant social brain circuits

An influential theory proposes that an imbalance between excitation and inhibition (E:I) plays a central role in the etiology of autism and related developmental disorders. However, controversy exists as to whether this imbalance is a direct causal mechanism for autism, or a compensatory response to other primary etiological factors. Using chemogenetic manipulations in neonatal mice, we show that a transient E:I imbalance during development is sufficient to permanently reprogram autism-relevant social brain circuits. Chemogenetically manipulated mice exhibit lifelong impairments in sociability, persistent dysregulation of multiple autism-risk synaptic genes, and sustained cortical hyperexcitability in adulthood. Importantly, these social impairments are robustly rescued by pharmacological inhibition of neuronal excitability. Developmental E:I imbalance also disrupts functional connectivity in social brain regions enriched for transcriptionally dysregulated genes, suggesting a convergence of transcriptional and circuit-level pathology. Finally, multivariate modelling shows that behavioral dysfunction in chemogenetically manipulated animals closely associates with disrupted connectivity between prefrontal and mesolimbic dopaminergic regions. Collectively, our findings reconcile conflicting theories in the field and point to activity-dependent transcriptional remodeling as a foundational mechanism by which transient E:I imbalance during development can cause lasting, autism-relevant circuit dysfunction.

neuroscience↗

bioRxiv2023

Heterogeneous subpopulations of GABAAR-responding neurons coexist in physiological and pathological mature neuronal networks at increasing scales of complexity

GABA is the main inhibitory neurotransmitter in adults. Depolarizing/excitatory GABA responses have been well characterized at the level of neuronal-population average during typical neurodevelopment and partially in pathology. However, no investigation has specifically assessed whether a mosaicism of cells with either depolarizing/excitatory or hyperpolarizing/inhibitory GABAergic responses exists in adult animals in health/disease. Here, we showed that such mosaicism is present both in adult WT and Down syndrome (DS) mice, as assessed at increasing scales of neuronal-network complexity (cultures, brain- slices, behaving mice). Nevertheless, WT mice presented a lower percentage of cells with depolarizing GABA than DS mice. Restoring the mosaicism of hyperpolarizing and depolarizing GABA-responding neurons to WT levels rescued anxiety behaviour in DS mice. We also found heterogeneous GABAergic responses in mature control and trisomic human iPSC-derived neurons. Thus, a heterogeneous population of GABA-responding cells exists in physiological/pathological conditions in mature mouse and human neurons, possibly contributing to disease-associated behaviours.

neuroscience↗

bioRxiv2020

Mosaic expression of X-linked PCDH19 Protein by in Utero Electroporation in Rats Replicates Human Cortical and Hippocampal Developmental Abnormalities, Associated Core Behaviors Related to Autism, and Cognitive Impairment.

PCDH19 gene-related epilepsy or epileptic encephalopathy, early infantile, 9 (EIEE9) is an infantile onset epilepsy syndrome characterized by psychiatric (including autistic) sensory and cognitive impairment of varying degrees. EIEE9 is caused by X-linked PCDH19 protein loss of function. Due to random X-chromosome inactivation, EIEE9-affected females present a mosaic population of healthy and Pcdh19-mutant cells. Unfortunately, no mouse models recapitulate to date both the brain histological and behavioural deficits present in people with EIEE9. Thus, the search for a proper understanding of the disease, and possible future treatment is hampered. By inducing a focal mosaicism of Pcdh19 expression using in utero electroporation in rat, we found here that Pcdh19 signaling in specific brain areas is implicated in neuronal migration, as well as in core behaviors related to autism and cognitive function.

neuroscience↗

bioRxiv2019

A Cre-amplifier to generate and detect genetic mosaics in vivo

Cre-Lox manipulation is the gold standard for cell-specific expression or knockout of selected genes. However, it is not unusual to deal with conditions of low Cre expression or transient activation, which can often go undetected by conventional Cre-reporters. We designed Beatrix, a general-purpose tool specifically devised to amplify weak Cre recombinase activity, and we used it to develop a powerful approach for the in vivo generation and detection of sparse mosaics of mutant and wild type cells.

neuroscience↗

bioRxiv2019

Gene editing preserves visual function in a mouse model of retinal degeneration

Inherited retinal dystrophies are a large and heterogeneous group of degenerative diseases caused by mutations in various genes. Given the favourable anatomical and immunological characteristics of the eye, gene therapy holds great potential for their treatment. We used a tailored CRISPR/Cas9-based gene editing system to prevent retinal photoreceptor death in the Rd10 mouse model of retinitis pigmentosa. We tested the gene editing tool in vitro and then used in vivo subretinal electroporation to deliver it to one of the retinas of mouse pups at different stages of photoreceptor differentiation. Three months after gene editing, the treated eye exhibited a higher visual acuity compared to the untreated eye. Moreover, we observed preservation of light-evoked responses both in explanted retinas and in the visual cortex of treated animals. Our study validates a CRISPR/Cas9-based therapy as a valuable new approach for the treatment of retinitis pigmentosa caused by autosomal recessive loss-of-function point mutations.

neuroscience↗