Alessandro Gozzi

Center for Neuroscience and Cognitive Systems

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Alberto Galbusera

Center for Neuroscience and Cognitive Systems

Angelo Bifone

University of Turin

Marco Pagani

Istituto Universitario di Studi Superiori di Pavia

Adam J. Schwarz

Children's Hospital of Orange County

Massimo Pasqualetti

Center for Neuroscience and Cognitive Systems

Ludovico Coletta

Italian Institute of Technology

Daniel Gutierrez‐Barragan

Center for Neuroscience and Cognitive Systems

Stefano Panzeri

University Medical Center Hamburg-Eppendorf

María Luisa Scattoni

Istituto Superiore di Sanità

Valerio Zerbi

ETH Zurich

Cooperative Institutions

Italian Institute of Technology

121

Centre National de la Recherche Scientifique

Inserm

GlaxoSmithKline (Italy)

Istituti di Ricovero e Cura a Carattere Scientifico

GlaxoSmithKline (United Kingdom)

Center for Neuroscience and Cognitive Systems

Allen Institute for Brain Science

University of Trento

Sapienza University of Rome

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Assessing the effects of dendritic spines plasticity using structural MRI on mice

Lorenza Brusini Federica Cruciani Ilaria Boscolo Galazzo Mirta Borin Giovanni Diana

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Altered Neocortical Gene Expression, Brain Overgrowth and Functional Over-Connectivity in Chd8 Haploinsufficient Mice

Cerebral Cortex (2018)

Philipp Suetterlin Shaun Hurley Conor Mohan Kimberley L. H. Riegman Marco Pagani

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 to social stimuli. Whereas gene expression in the neocortex is only mildly affected at midgestation, over 600 genes are differentially expressed in the early postnatal neocortex. Genes involved in cell adhesion and axon guidance are particularly prominent amongst the downregulated transcripts. Resting-state functional MRI identified increased synchronized activity in cortico-hippocampal and auditory-parietal networks in Chd8 heterozygous mutant mice, implicating altered connectivity as a potential mechanism underlying the behavioral phenotypes. Together, these data suggest that altered brain growth and diminished expression of important neurodevelopmental genes that regulate long-range brain wiring are followed by distinctive anomalies in functional brain connectivity in Chd8+/− mice. Human imaging studies have reported altered functional connectivity in ASD patients, with long-range under-connectivity seemingly more frequent. Our data suggest that CHD8 haploinsufficiency represents a specific subtype of ASD where neuropsychiatric symptoms are underpinned by long-range over-connectivity.

Haploinsufficiency

Neocortex

10.1093/cercor/bhy058

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Citations (108)

Evolutionarily conserved fMRI network dynamics in the mouse, macaque, and human brain

Nature Communications (2024)

Daniel Gutierrez‐Barragan Julian S.B. Ramirez Stefano Panzeri Ting Xu Alessandro Gozzi

Evolutionarily relevant networks have been previously described in several mammalian species using time-averaged analyses of fMRI time-series. However, fMRI network activity is highly dynamic and continually evolves over timescales of seconds. Whether the dynamic organization of resting-state fMRI network activity is conserved across mammalian species remains unclear. Using frame-wise clustering of fMRI time-series, we find that intrinsic fMRI network dynamics in awake male macaques and humans is characterized by recurrent transitions between a set of 4 dominant, neuroanatomically homologous fMRI coactivation modes (C-modes), three of which are also plausibly represented in the male rodent brain. Importantly, in all species C-modes exhibit species-invariant dynamic features, including preferred occurrence at specific phases of fMRI global signal fluctuations, and a state transition structure compatible with infraslow coupled oscillator dynamics. Moreover, dominant C-mode occurrence reconstitutes the static organization of the fMRI connectome in all species, and is predictive of ranking of corresponding fMRI connectivity gradients. These results reveal a set of species-invariant principles underlying the dynamic organization of fMRI networks in mammalian species, and offer novel opportunities to relate fMRI network findings across the phylogenetic tree.

Rhesus macaque

Nerve net

Dynamics

Human brain

10.1038/s41467-024-52721-8

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Citations (3)

Sex-biasing influence of autism-associated Ube3a gene overdosage at connectomic, behavioral, and transcriptomic levels

Science Advances (2024)

Caterina Montani Luigi Balasco Marco Pagani Filomena Grazia Alvino Noemi Barsotti

Genomic mechanisms enhancing risk in males may contribute to sex bias in autism. The ubiquitin protein ligase E3A gene ( Ube3a ) affects cellular homeostasis via control of protein turnover and by acting as transcriptional coactivator with steroid hormone receptors. Overdosage of Ube3a via duplication or triplication of chromosomal region 15q11-13 causes 1 to 2% of autistic cases. Here, we test the hypothesis that increased dosage of Ube3a may influence autism-relevant phenotypes in a sex-biased manner. We show that mice with extra copies of Ube3a exhibit sex-biasing effects on brain connectomics and autism-relevant behaviors. These effects are associated with transcriptional dysregulation of autism-associated genes, as well as genes differentially expressed in 15q duplication and in autistic people. Increased Ube3a dosage also affects expression of genes on the X chromosome, genes influenced by sex steroid hormone, and genes sex-differentially regulated by transcription factors. These results suggest that Ube3a overdosage can contribute to sex bias in neurodevelopmental conditions via influence on sex-differential mechanisms.

UBE3A

Angelman Syndrome

10.1126/sciadv.adg1421

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A consensus protocol for functional connectivity analysis in the rat brain

Nature Neuroscience (2023)

Joanes Grandjean Gabriel Desrosiers-Grégoire Cynthia Anckaerts Diego Ángeles-Valdéz Fadi Ayad

Modalities

10.1038/s41593-023-01286-8

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Citations (59)

Metastatic cancer and endentulism: Exploring comorbidity to assist with differential diagnosis in a case from Vico nel Lazio (Fr, Italy), 13th-15th century CE

International Journal of Paleopathology (2022)

Mauro Rubini Alessandro Gozzi Nunzia Libianchi Elena Rosangela Dellu Ferdinando Spanò

Edentulism

Postcrania

10.1016/j.ijpp.2022.05.005

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Citations (2)

Modulation of Fronto-Cortical Activity by Modafinil: A Functional Imaging and Fos Study in the Rat

Neuropsychopharmacology (2011)

Alessandro Gozzi Valeria Colavito Paul F. Seke Etet Dino Montanari Silvia Fiorini

10.1038/npp.2011.260

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Citations (47)

Functional and Pharmacological MRI in Understanding Brain Function at a Systems Level

Current topics in behavioral neurosciences (2011)

Angelo Bifone Alessandro Gozzi

Neurotransmitter Systems

Human brain

Preclinical research

Brain Function

Translational Research

10.1007/7854_2010_103

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Citations (12)

Antagonism at serotonin 5-HT2A receptors modulates functional activity of frontohippocampal circuit

Psychopharmacology (2010)

Alessandro Gozzi Valerio Crestan Giuliano Turrini M. S. Clemens Angelo Bifone

Serotonin Antagonists

10.1007/s00213-009-1772-4

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Citations (32)

Unique spatiotemporal fMRI dynamics in the awake mouse brain

bioRxiv (Cold Spring Harbor Laboratory) (2021)

Neha Atulkumar Singh Daniel Gutierrez‐Barragan Filomena Grazia Alvino Ludovico Coletta Federico Rocchi

Abstract Human imaging studies have shown that spontaneous brain activity exhibits stereotypic spatiotemporal reorganization in awake, conscious conditions with respect to minimally conscious states. However, whether and how this phenomenon can be generalized to lower mammalian species, remains unclear. Leveraging a robust protocol for resting-state fMRI (rsfMRI) mapping in non-anesthetized, head-fixed mice, we investigated functional network topography and dynamic structure of spontaneous brain activity in wakeful animals. We found that rsfMRI networks in the awake state, while anatomically comparable to those observed under anesthesia, are topologically configured to maximize interregional communication, departing from the underlying community structure of the mouse axonal connectome. We further report that rsfMRI activity in wakeful animals exhibits unique spatiotemporal dynamics characterized by a state-dependent, dominant occurrence of coactivation patterns encompassing a prominent participation of arousal-related forebrain nuclei, and functional anti-coordination between visual-auditory and polymodal cortical areas. We finally show that rsfMRI dynamics in awake mice exhibits a stereotypical temporal structure, in which state-dominant coactivation patterns are configured as network attractors. These findings suggest that spontaneous brain activity in awake mice is critically shaped by state-specific involvement of basal forebrain arousal systems, and document that its dynamic structure recapitulates distinctive, evolutionarily-relevant principles that are predictive of conscious states in higher mammalian species.

Forebrain

Coactivation

Nerve net

10.1101/2021.08.24.457302

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