The Functional Neuroimaging Laboratory focuses on the study of mammalian brain organization at the macroscale.
We are interested in understanding how large scale functional activity and network dynamics originate, develop and govern behavioural states. A major goal of our research is to unravel the elusive neurophysiological basis of macroscale functional connectivity as measured with neuroimaging methods, and the underpinnings of its aberrations observed in human brain disorders such as autism spectrum disorders. To achieve these goals, we have pioneered the use of advanced magnetic resonance magnetic (MRI) methods to image the structure and function of the living mouse brain under resting conditions, or upon pharmacological, neuromodulatory or genetic preconditioning. The combined use of high resolution structural (e.g. Diffusion Tensor imaging - DTI and voxel-based morphometry -VBM) and functional MRI (fMRI) defines a novel investigational platform that we have successfully employed to describe the intrinsic organization of the mouse brain in unprecedented detail. We aim to combine these novel approaches with cell type-specific optogenetic manipulations to establish causal relationship between local activity and its propagation at the systems level.
Macroscale functional organization of the mouse brain
This research leverages on the use of resting-state fMRI to obtain an integrated portrayal of the macroscale mouse functional connectome, i.e. the complex network of elements and connections that govern and compose the brain at the macroscale. As part of this effort, we provided the first demonstration of the presence of distributed resting-state functional connectivity networks in the mouse brain including a plausible homologue of the human salience and default mode network (DMN). We are now using multidisciplinary approaches to investigate the function, behavioural relevance and directional topology of the mouse DMN and other connectivity networks via the use of canonical and advanced computational frameworks, including multivariate Granger Causality and dynamic causal modelling. Our efforts complement ongoing activities aimed at mapping the macroscale organization of the laboratory mouse, with the final goal of describe brain function as the integration of processes occurring at multiple scales.
- Stefano Panzeri, Neural Computation, IIT.
- Michele Caselle, University of Torino.
Neurobiological basis of aberrant functional connectivity in autism
Deficits in large-scale structural and functional connectivity have been highlighted for autistic patient populations, but investigational approaches to unravel the elusive pathophysiological basis and significance of these phenomena are limited. By using fMRI in transgenic mouse lines mouse we have begun to establish causal relationships between genetic ASD-related mutations, neurodevelopmental processes and functional connectivity alterations. This line of research will provide testable hypotheses concerning the mechanisms underlying a key patho-physiological feature of autism, thus shedding light into the origin and clinical significance of these aberrations. Importantly, the use of readouts commonly used in the clinic offers a means to translate our findings from and to analogous patient populations.
- Massimo Pasqualetti, University of Pisa.
- Alessandro Usiello, Cienge Napoli.
- Maria Luisa Scattoni, ISS, University of Torino.
Endogenous modulation of functional connectivity
At the cellular level, local functional connections giving rise to a specific circuit output are configured by neuromodulatory environment. According to this view, axonal connectivity itself only establishes potential circuit configurations, whose availability and properties depend critically on local neuromodulatory state. However the degree to which similar dynamics may shape macroscale intrinsic brain function remains unknown. We are using optogenetic methods to determine the role of endogenous neuromodulation in shaping network activity as measured with resting state fMRI. Our research will help understand how local neuronal perturbation propagate at the network level, and the degree to which alterations in internal states affect macroscale network configurations
- Massimo Pasqualetti, University of Pisa.
- Ferruccio Pisanello, IIT Lecce.
The Functional Neuroimaging Laboratory is equipped with state-of-the-art instrumentation for
- Structural and functional brain imaging (7 Tesla multi-channel MRI scanner, high resolution microendoscopic probes and optical systems for recording the brain intrinsic signal)
- Electrophysiology (dual-channel patch-clamp amplifiers and multichannel extracellular amplifiers)
- Optogenetics (laser sources and optical devices for single- and two-photon patterned excitation)
- Transgene expression (transgenic Cre-lox models and various gene delivery approaches)
Large-scale functional connectivity networks in the rodent brain Gozzi A, Schwarz AJ. Neuroimage. 2015 Dec 17. pii: S1053-8119(15)01130-1. doi: 10.1016/j.neuroimage.2015.12.017. [Epub ahead of print] (2015)
Functional connectivity hubs of the mouse brain Liska A, Galbusera A, Schwarz AJ, Gozzi A Neuroimage. 2015 Jul 15;115:281-91. doi: 10.1016/j.neuroimage.2015.04.033. Epub 2015 Apr 23. (2015)
Altered functional connectivity networks in acallosal and socially impaired BTBR mice Sforazzini F, Bertero A, Dodero L, David G, Galbusera A, Scattoni ML, Pasqualetti M, Gozzi A. Brain Struct Funct. 2014 Dec 2 (2014)
Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior Zhan Y, Paolicelli RC, Sforazzini F, Weinhard L, Bolasco G, Pagani F, Vyssotski AL, Bifone A, Gozzi A, Ragozzino D, Gross CT Nat Neurosci. 2014 Mar;17(3):400-6. doi: 10.1038/nn.3641. Epub 2014 Feb 2. (2014)
Distributed BOLD and CBV-weighted resting-state networks in the mouse brain Sforazzini F, Schwarz AJ, Galbusera A, Bifone A, Gozzi A Neuroimage. 2014 Feb 15;87:403-15. doi: 10.1016/j.neuroimage.2013.09.050. Epub 2013 Sep 29. (2014)