A5026729858- Functional Brain Connectivity Studies
- Neural dynamics and brain function
- Autism Spectrum Disorder Research
- Genetics and Neurodevelopmental Disorders
- Congenital heart defects research
- Neuroscience and Neuropharmacology Research
- Neuroendocrine regulation and behavior
- Advanced MRI Techniques and Applications
- Photoreceptor and optogenetics research
- Advanced Neuroimaging Techniques and Applications
- Neuroscience of respiration and sleep
- Amino Acid Enzymes and Metabolism
- Infant Health and Development
- Diet and metabolism studies
- Embedded Systems Design Techniques
- Epigenetics and DNA Methylation
- VLSI and FPGA Design Techniques
- EEG and Brain-Computer Interfaces
- Congenital Heart Disease Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Stress Responses and Cortisol
- Adipose Tissue and Metabolism
- Barrier Structure and Function Studies
- Neuroscience and Neural Engineering
- Adenosine and Purinergic Signaling
Center for Neuroscience and Cognitive Systems
2016-2025
Italian Institute of Technology
2016-2025
University of Trento
2017-2021
ORCID
2021
Università della Svizzera italiana
2003
Politecnico di Milano
2003
Abstract Postmortem studies have revealed increased density of excitatory synapses in the brains individuals with autism spectrum disorder (ASD), a putative link to aberrant mTOR-dependent synaptic pruning. ASD is also characterized by atypical macroscale functional connectivity as measured resting-state fMRI (rsfMRI). These observations raise question whether excess causes ASD. Using rsfMRI, electrophysiology and silico modelling Tsc2 haploinsufficient mice, we show that spine associated...
Human imaging studies have shown that spontaneous brain activity exhibits stereotypic spatiotemporal reorganization in awake, conscious conditions with respect to minimally states. However, whether and how this phenomenon can be generalized lower mammalian species remains unclear. Leveraging a robust protocol for resting-state fMRI (rsfMRI) mapping non-anesthetized, head-fixed mice, we investigated functional network topography dynamic structure of wakeful animals. We found rsfMRI networks...
Abstract While shaped and constrained by axonal connections, fMRI-based functional connectivity reorganizes in response to varying interareal input or pathological perturbations. However, the causal contribution of regional brain activity whole-brain fMRI network organization remains unclear. Here we combine neural manipulations, resting-state vivo electrophysiology probe how inactivation a cortical node causally affects brain-wide coupling mouse. We find that chronic inhibition medial...
Human genetic studies are rapidly identifying variants that increase risk for neurodevelopmental disorders. However, it remains unclear how specific mutations impact brain function and contribute to neuropsychiatric risk. Chromosome 16p11.2 deletion is one of the most common copy number variations in autism related Using resting state functional MRI data from Simons Variation Individuals Project (VIP) database, we show carriers exhibit impaired prefrontal connectivity, resulting weaker...
BTBR T+tf/J (BTBR) mice display prominent behavioural deficits analogous to the defining symptoms of autism, a feature that has prompted widespread use model in preclinical autism research. Because neuro-behavioural traits are described with respect reference populations, multiple investigators have examined and behaviour against exhibited by C57BL/6J (B6), mouse line characterised high sociability low self-grooming. In an attempt probe translational relevance this comparison for research,...
Truncating CHD8 mutations are amongst the highest confidence risk factors for autism spectrum disorder (ASD) identified to date. Here, we report that Chd8 heterozygous mice display increased brain size, motor delay, hypertelorism, pronounced hypoactivity, and anomalous responses social stimuli. Whereas gene expression in neocortex is only mildly affected at midgestation, over 600 genes differentially expressed early postnatal neocortex. Genes involved cell adhesion axon guidance particularly...
Functional connectivity aberrancies, as measured with resting-state functional magnetic resonance imaging (rsfMRI), have been consistently observed in the brain of autism spectrum disorders (ASD) patients. However, genetic and neurobiological underpinnings these findings remain unclear. Homozygous mutations contactin associated protein-like 2 (CNTNAP2), a neurexin-related cell-adhesion protein, are strongly linked to epilepsy. Here we used rsfMRI show that homozygous mice lacking Cntnap2...
Mutations in the synaptic scaffolding protein SHANK3 are a major cause of autism and associated with prominent intellectual language deficits. However, neural mechanisms whereby deficiency affects higher-order socio-communicative functions remain unclear. Using high-resolution functional structural MRI adult male mice, here we show that loss <i>Shank3</i> (<i>Shank3B</i><sup>−/−</sup>) results disrupted local long-range prefrontal frontostriatal connectivity. We document hypoconnectivity is...
Autism Spectrum Disorder (ASD) is characterized by substantial, yet highly heterogeneous abnormalities in functional brain connectivity. However, the origin and significance of this phenomenon remain unclear. To unravel ASD connectopathy relate it to underlying etiological heterogeneity, we carried out a bi-center cross-etiological investigation fMRI-based connectivity mouse, which specific ASD-relevant mutations can be isolated modeled minimizing environmental contributions. By performing...
It is frequently assumed that the phenotypic heterogeneity in autism spectrum disorder reflects underlying pathobiological variation. However, direct evidence support of this hypothesis lacking. Here, we leverage cross-species functional neuroimaging to examine whether variability brain connectivity distinct biological mechanisms. We find fMRI alterations 20 mouse models (n=549 individual mice) can be clustered into two prominent hypo- and hyperconnectivity subtypes. show these profiles are...
Serotonin-producing neurons profusely innervate brain regions via long-range projections. However, it remains unclear whether and how endogenous serotonergic transmission specifically influences regional or global functional activity. We combined designed receptors exclusively activated by drugs (DREADD)-based chemogenetics magnetic resonance imaging (fMRI), an approach we term "chemo-fMRI," to causally probe the brain-wide substrates modulated describe generation of a conditional knockin...
Human and experimental studies have revealed putative neuroprotective pro-cognitive effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) in aging, evidencing positive correlations between peripheral n-3 PUFA levels regional grey matter (GM) volume, as well negative dietary cognitive deficits. We recently showed that supplemented aged mice exhibit better hippocampal-dependent mnesic functions, along with enhanced cellular plasticity reduced neurodegeneration, thus supporting a role...
Overreactivity and defensive behaviors in response to tactile stimuli are common symptoms autism spectrum disorder (ASD) patients. Similarly, somatosensory hypersensitivity has also been described mice lacking ASD-associated genes such as
Genomic mechanisms enhancing risk in males may contribute to sex bias autism. The ubiquitin protein ligase E3A gene ( Ube3a ) affects cellular homeostasis via control of turnover and by acting as transcriptional coactivator with steroid hormone receptors. Overdosage duplication or triplication chromosomal region 15q11-13 causes 1 2% autistic cases. Here, we test the hypothesis that increased dosage influence autism-relevant phenotypes a sex-biased manner. We show mice extra copies exhibit...
Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by pronounced social and communication deficits stereotyped behaviours. Recent psychosocial neuroimaging studies have highlighted reward-processing reduced dopamine (DA) mesolimbic circuit reactivity in ASD patients. However, the neurobiological molecular determinants of these remain undetermined. Mouse models recapitulating ASD-like phenotypes could help generate hypotheses about origin neurophysiological...
Genetic variations in catechol-O-methyltransferase (COMT) that modulate cortical dopamine have been associated with pleiotropic behavioral effects humans and mice. Recent data suggest some of these may vary among sexes. However, the specific brain substrates underlying COMT sexual dimorphisms remain unknown. Here, we report genetically driven reduction enzyme activity increased thickness prefrontal cortex (PFC) postero-parieto-temporal male, but not female adult mice humans. Dichotomous...
D-aspartate (D-Asp) is an atypical amino acid, which especially abundant in the developing mammalian brain, and can bind to activate N-methyl-D-Aspartate receptors (NMDARs). In line with its pharmacological features, we find that mice chronically treated D-Asp show enhanced NMDAR-mediated miniature excitatory postsynaptic currents basal cerebral blood volume fronto-hippocampal areas. addition, both chronic administration of deletion gene coding for catabolic enzyme oxidase (DDO) trigger...
Autism spectrum disorders (ASD) and epilepsy are neurodevelopmental conditions that appear with high rate of co-occurrence, suggesting the possibility a common genetic basis. Mutations in Synapsin (SYN) genes, particularly SYN1 SYN2, have been recently associated ASD humans. Accordingly, mice lacking Syn1 or Syn2, but not Syn3, experience epileptic seizures display autistic-like traits precede onset seizures. Here, we analyzed social behavior ultrasonic vocalizations emitted 2 contexts by...
Abstract Abnormal tactile response is an integral feature of Autism Spectrum Disorders (ASDs), and hypo-responsiveness to stimuli often associated with the severity ASDs core symptoms. Patients Phelan-McDermid syndrome (PMS), caused by mutations in SHANK3 gene, show ASD-like symptoms aberrant responses. The neural underpinnings these abnormalities are still poorly understood. Here we investigated, Shank3b−/− adult mice, substrates whisker-guided behaviors, a key component rodents’...