NICO NeuroWebinar 2021

NeuroWebinar 2021

17/12/21 - Progress report
Giulia Nato (Group Bonfanti-Peretto)
Role of SOX2 in the modulation of striatal astrocytes neurogenic potential.

10/12/21 - Progress report
Gioriga Iegiani (Group Di Cunto)
CITK loss leads to DNA damage accumulation impairing homologous recombination by BRCA1 mislocalization 

3/12/21 - Progress report
  Serena Stanga (Group Vercelli)
Aconitase2 is a marker of mitochondrial dysfunctions in Spinal Muscular Atrophy spinal cord and fibroblasts

25/11/21 -  Lecture  
Antonio Rodríguez-Moreno
Departamento de Fisiología, Anatomía y Biología Celular - Universidad Pablo de Olavide (Sevilla)

Changes in plasticity during postnatal development. Opening and closing plasticity windows
Critical periods of synaptic plasticity facilitate the reordering and refining of neural connections during development, allowing the definitive synaptic circuits responsible for correct adult physiology to be established. Presynaptic spike timing-dependent long-term depression (t-LTD) exists in the hippocampus, which depends on the activation of NMDARs and that probably fulfills a role in synaptic refinement. This t-LTD is present until the third postnatal week in mice, disappearing in the fourth week of postnatal development. We were interested in the mechanisms underlying this maturation related loss of t-LTD. At more mature stages, we found that the protocol that induced t-LTD induced t-LTP. We characterized this form of t-LTP and the mechanisms involved in its induction, as well as that driving this switch from t-LTD to t-LTP.
Host: Carola Eva

19/11/21 at 2.00 pm -  Lecture  
  Alessandro Fiorenzano, PhD
Lund University (SWE)

From advanced cell culture studies to a stem cell therapy for Parkinson´s disease
Three-dimensional (3D) brain organoids have emerged as a valuable model system for studies of human brain development and pathology. We established a midbrain organoid culture system to study  dopamine neuron differentiation trajectory at single cell resolution. Additionally,  we are combining single-cell RNA sequencing with histological analyses to characterise intracerebral grafts from human pluripotent stem cells and fetal tissue after functional maturation in a pre-clinical rat PD model. This study uncovers previously unknown cellular diversity in a clinically relevant cell replacement PD model.
Host: Roberta Schellino

18/11/21 at 4.30 pm -  Lecture  
  Letizia Marvaldi
Weizmann Institute of Science, Israel

Importin α3 regulates chronic pain pathways in peripheral sensory neurons
How is neuropathic pain regulated in peripheral sensory neurons? Importins are key regulators of nucleocytoplasmic transport. In this study, we found that importin α3 (also known as karyopherin subunit alpha 4) can control pain responsiveness in peripheral sensory neurons in mice. Importin α3 knockout or sensory neuron-specific knockdown in mice reduced responsiveness to diverse noxious stimuli and increased tolerance to neuropathic pain. 
Importin α3-bound c-Fos and importin α3-deficient neurons were impaired in c-Fos nuclear import. Knockdown or dominant-negative inhibition of c-Fos or c-Jun in sensory neurons reduced neuropathic pain. In silico screens identified drugs that mimic importin α3 deficiency. These drugs attenuated neuropathic pain and reduced c-Fos nuclear localization. Thus, perturbing c-Fos nuclear import by importin α3 in peripheral neurons can promote analgesia.
Host: Alessandro Vercelli

5/11/21 at 2.00 pm -  Lecture  
  Wannan Tang
Department of Clinal and Molecular Medicine (IKOM), Norwegian University of Science and Technology (NTNU), Norway

Dissecting neuronal-glial cross-talk
Accumulating evidence in the recent decade indicates that the long neglected glial cells are tightly engaged in brain network function. However, up to now, it is not established how glial activities are modulating neuronal circuit function. In modern Neurophysiology, the use of genetically encoded fluorescent sensors and opto-/chemogenetic manipulation of neurons allowed to identify the generation of neuronal circuits in the forebrain that are critically involved in the learning of specific behaviors. There is emerging evidence that the glial cells are actively involved and necessary for the establishment of these circuits. In our study, we aim to analyze glial physiology and neuronal-glial communication in the mouse brain using and developing novel genetically encoded fluorescent sensors, chemogenetic and optogenetic approaches in the mouse brain both ex vivo and in vivo. Our studies utilize virally delivered genetically encoded fluorescent sensors of various molecules for glial physiology studies in the acute brain slices, as well as for head-fixed awake mice under behavioral tasks in combination with two-photon microscopy.
Host: Ilaria Bertocchi

15/10/21 - Progress report
  Sara Bonzano (Group Bonfanti-Peretto)
Nr2f1 shapes mitochondrial architecture in adult-born mouse hippocampal neurons by regulating nuclear encoded mitochondrial factors

8/10/21 - Progress report
  Valeria Vasciaveo (Group Vercelli)
Alzheimer’s disease and sleep fragmentation: electroencephalography and bimolecular studies in mouse models

17/9/21 - Progress report
  Cecilia Bava (Group Capobianco)
Simoa technology for the quantification of serum neurofilaments in multiple sclerosis patients

10/9/21 - Lecture
Frédéric Clotman
Université catholique de Louvain, Belgium

Carrot and stick: paralog factors orchestrate neuronal differentiation in the developing spinal cord
Cell differentiation models involve activation of specific differentiation programs, or repression of alternative fates, or a combination of both. The transcriptional regulators that orchestrate neuronal differentiation often belong to multigenic families that produce paralog factors in the same cells or in the same cell lineages. Specific contribution of these paralog factors in cell fate decision is frequently underestimated.
In the developing spinal cord, LIM-homeodomain transcription factors promote the differentiation of motor neurons or V2 interneurons, while homeodomain-containing transcriptional repressors prevent irrelevant activation of the alternative differentiation program. I will show that paralog factors may differently contribute to these processes, either in the same cells or in distinct populations of the same lineage, underlining the necessity to precisely characterize the contribution of paralog factors to biological processes and to integrate this information for in vitro differentiation of transplantation-competent neuronal cells.
Host: Serena Stanga

23/7/21 - Progress report
  Gianmarco Pallavicini (Group Di Cunto)
Targeting Microcephaly genes in Brain Tumors

16/7/21 - Progress report
  Marco Ghibaudi (Group Bonfanti/Peretto)
Immature" neurons in subcortical regions of different mammals

9/7/21 - Lecture
Mazahir T. Hasan
Ikerbasque Institute - Lab of Brain Circuits Therapeutics, Bilbao (Spain)

Synaptic to brain wide organization of memory engram
My research interest is to reveal the organization of memory engram in the brain and develop innovative approaches for brain circuit therapeutics to treat neurological and psychiatric diseases. Although classic evidence by Karl Lashley had demonstrated in the 1950s that specific memories are widely distributed in the brain, it is however still not well understood that ‘where’ and ‘how’ memories of our experiences are printed in the brain. To tackle these important questions in systems neuroscience research, it is imperative to map input/out connectivity between the different brain regions and reveal the circuits that are recruited for learning, memory formation, storage and retrieval. My lab has developed and continues to develop novel genetic technologies to manipulate and map functional circuits. In my talk, I will highlight my key scientific contributions and the current ongoing projects to reach our research goals.
Host: Ilaria Bertocchi

2/7/21 - Progress report
  Anna Caretto (Group Vercelli)
The role of the GHRH agonist MR409 in a mouse model of Spinal Muscular Atrophy

25/6/21 - Progress report
  Roberta Parolisi (Group Buffo)
Air pollution and Multiple Sclerosis: role of particulate matter (PM) exposure in neuroinflammation and demyelination

18/6/21 - Lecture
Federico Rossi, University College London

Spatial connectivity matches direction selectivity in visual cortex
The selectivity of neuronal responses arises from the architecture of excitatory and inhibitory connections. In the primary visual cortex, the selectivity of layer 2/3 neurons for stimulus orientation and direction is thought to arise from similarly-selective intracortical inputs. A neuron’s excitatory inputs, however, can have diverse stimulus preferences, and inhibitory inputs can be promiscuous and unselective. We revealed that excitatory and inhibitory intracortical connections to a layer 2/3 neuron accord with its selectivity by obeying precise spatial patterns (Rossi et al., Nature, in press).
We used rabies tracing to label and functionally image the excitatory and inhibitory inputs to individual pyramidal neurons of mouse visual cortical layer 2/3. Presynaptic excitatory neurons spanned layers 2/3 and 4 and were distributed coaxial to the postsynaptic neuron’s preferred orientation, favouring the region opposite to its preferred direction. By contrast, presynaptic inhibitory neurons resided within layer 2/3 and favoured locations near the postsynaptic neuron and ahead of its preferred direction. The direction selectivity of a postsynaptic neuron was unrelated to the selectivity of presynaptic neurons but correlated with the spatial displacement between excitatory and inhibitory presynaptic ensembles. Similar asymmetric connectivity establishes direction selectivity in the retina, suggesting that this circuit motif might be canonical in sensory processing.
We are currently discovering similar patterns also in the dendritic morphology of the postsynaptic neurons, whose dendrites that extend along the neurons’ preferred orientation appear to receive most of the orientation selective inputs (Rossi et al., FENS 2020 Abstract). These results suggest a link between the dendritic architecture and the function of V1 neurons: by extending towards the appropriate inputs, dendrites may provide a morphological substrate for the emergence of visual selectivity.
Host: Stefano Zucca

11/6/21 - Progress report
  Daniela Rasà (Group Vercelli)
Drug repositioning for SMA treatment: from worms to in vitro screening of six hit-compounds in mouse primary cortical neurons

4/6/21 - Lecture
Catherine Perrodin
Institute of Behavioural Neuroscience, University College London

I like the way you sing – Neural systems for vocal perception
Effectively interpreting communication sounds from others is essential for our social interactions and survival. My research develops animal models to study the neuronal mechanisms of vocal perception. Following past work on voice processing in the primate brain, my current work in mice utilizes male-female courtship interactions to study the processing of complex vocal sequences. In my talk I will present recent work based on natural mouse behaviour that highlights the importance of temporal patterns in vocal communication. I will then talk about ongoing work investigating the neuronal substrates supporting vocal sequence processing in the brain of the listener.
Host: Serena Bovetti

28/5/21 - Progress report
  Marco Fogli (Group Peretto)
Transient neurogenic niches are generated by the sparse and asynchronous activation of striatal astrocytes after excitotoxic lesion

21/5/21 - Progress report
  Giovanna Menduti (Group Vercelli)
Drug repositioning as a strategy to develop new therapeutic approaches for Spinal muscular atrophy

14/5/21 - Lecture
Sergio Casas Tintó
Instituto Cajal-CSIC - Madrid, Spain

Cell to cell communication mediates glioblastoma progression and neurodegeneration
Glioblastoma (GB) is the most aggressive and frequent primary brain tumor.Current treatments include radio-, chemotherapy and surgical resection of the solid core of the tumor. However, almost 100% of the patients undergo relapses and median survival is 16 months. GB mutations can be very heterogeneous but PI3K and EGFR pathways are the most frequently mutated. GB cells produce cellular protrusions known as Tumor Microtubes (TMs) or cytonemes that facilitate tumor expansion and cellular interaction with healthy neurons.
Our projects are focused in the study of GB-neuron molecular interactions that contribute to GB-induced lethality. In this seminar I will present data on the contribution of WNT pathway and Insulin Receptor (InR) signaling to GB progression.
TMs accumulate specific Frizzled receptors that contribute to the depletion of WNT from surrounding neurons. This imbalance in WNT pathway causes JNK pathway activation and Matrix Metalloproteases (MMPs) secretion, MMPs degrade extracellular matrix and facilitates further TMs expansion. In consequence of WNT depletion, neurons undergo synapse loss and neurodegeneration that contribute significantly to the premature death caused by GB.
Besides, GB cells also produce ImpL2, an antagonist of the Insulin receptor known as IGFBP7 in humans. ImpL2 is secreted and impact on neighboring neurons, inconsequence Insulin pathway is repressed, causes mitochondrial defects and synapse loss. Restoration of InR signaling in neurons counteracts neurodegenerative effects of GB.
Host: Silvia De Marchis

7/5/21 - Lecture
Chiara Tonda-Turo
PolitoBIOmedLAB, Department of Mechanical and Aerospace Engineering, Politecnico di Torino

Engineering meets biology to design biomimetic and bioactive scaffolds to modulate cell fate
Biomimetic and bioactive scaffolds represent the ideal interface to steer cell response in the field of tissue engineering. Among them, nanofibrous membranes and smart hydrogels have emerged for their great potential as biomimetic and bioactive interfaces thanks to their close structural resemblance to the ECM (which enhances the tissue growth) showing a high potential to facilitate the formation of artificial functional tissues. 
Furthermore, current trends in scaffold development aim to develop experimental in vitro models that can reproduce the behaviour of the human tissues by applying the principles of tissue engineering. Experimental in vitro models offer the unique potential to combine the features of the engineered system-scaffold with the biological actors of tissues and organs, achieving the final goal of recapitulating the complex human physiology in vitro.
In this seminar, the fabrication and characterisation of natural-based nanofibers and smart hydrogels is discussed highlighting the role of biomimetic 3D architectures and functional cues on cell fate in the field of nerve fiber regeneration. Also, in vitro models recently established at POLITO are presented and the perspectives to recreate complex neuronal structures such as the spinal cord are discussed. 
Host: Marina Boido

30/4/21 - Progress report
  Chiara La Rosa (Group Peretto)
Imaging the mouse developing auditory cortex

23/4/21 - Progress report
Martina Lorenzati (Group Buffo)
hiPSCs manteinance and glial committment: a technical report

16/4/21 - Lecture
Alessandra Griffa, PhD 
Department of Clinical Neuroscience, Division of Neurology, Geneva University Hospital and Faculty of Medicine, Geneva

Understanding symptom reversibility in idiopathic Normal Pressure Hydrocephalus with multimodal MR brain imaging
Idiopathic Normal Pressure Hydrocephalus (iNPH) isa progressive neurodegenerative disorder characterized by gait, cognitive and urinary impairments with ventriculomegaly at brain imaging. With up to 80% of patients improving after a shunt procedure, iNPH is considered the leading cause of reversible dementia in aging. However, despite its high prevalence estimated at 6% among the elderlies, iNPH remains underdiagnosed and undertreated due to lack of iNPH-specific diagnostic and prognostic markers and limited understanding of neuropathophysiological mechanisms. INPH diagnosis is also complicated by the frequent occurrence of comorbidities, the most common one being Alzheimer’s disease. Multimodal magnetic resonance brain imaging, including functional, diffusion and perfusion imaging, can shed light on macroscale brain changes associated with iNPH pathophysiology and symptom reversibility.
In this talk, I will summarize our results on system-level brain functional alterations in iNPH, their relation to clinical symptoms and to plasticity mechanisms occurring after cerebrospinal fluid removal with lumbar puncture. I will discuss the role of comorbid Alzheimer’s pathology on iNPH symptom reversibility and multimodal magnetic resonance imaging approaches for prediction of iNPH treatment outcome and translational research.
Host: Corrado Calì

12/4/21  - Lecture 
Gabriela Berenice Gómez González, PhD, MsC 
Laboratory of Molecular and cellular Neurobiology, Instituto de Neurociencias, UNAM, Mexico

Inter-fastigial connections along the roof of the fourth ventricle in the mouse
The roof of the fourth ventricle, specifically the subventricular zone represents a complex region given the heterogeneity of cells that integrates the zone, including a dense array of myelinic axons with unknown anatomical origin. We show that this tract of axons, named subventricular axons or SVa, contains projection neurons that bilaterally interconnect both FNs. The Fastigial Nucleus (FN) is one of the three deep cerebellar nuclei and has been related in a plethora of motor and non-motor functions, for instance, saccadic and vestibular control, social behavior, blood pressure and intestinal motility. Highlighting the high connectivity of this nuclei and its impact at central and peripheral level.
The approach consisted of the use of a battery of fluorescent neuronal tracers, transgenic mouse lines, and immunohistofluorescence. Our observations show that the SVa belong to a wide network of GABAergic projection neurons mainly located in the medial and caudal region of the FN. The SVa should be considered a part of a continuum of the cerebellar white matter that follows an alternative pathway through the SVZ, a region closely associated with the physiology of the fourth ventricle. This finding adds to our understanding of the complex organization of the FN; however, the function of that interconnection remains to be elucidated.
Host: Annalisa Buffo

9/4/21 - Lecture
Claudio Moretti
Laboratoire Kastler Brossel / CNRS - Paris

Imaging in deep: the good, the bad, and the scattering
Fluorescence functional imaging is a key tool in neuroscience, which allows to study complex integration and processing of information across the brain circuitry in the rodent model. However, light scattering in brain tissues is considered nowadays the main obstacle from recording in deep structures. In this talk I will discuss some approaches which enable deep to brain imaging, by rejecting, evading, and exploiting scattering.
Host: Serena Bovetti

26/3/21 - Lecture
Paolo Giacobini
Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Postnatal Brain, Lille Neuroscience & Cognition

3D-imaging after clearing: theory and applications
Traditional histological examination of brain systems and networks has long relied on tissue sectioning and analyses of thin serial slices that presents limitations for large volumetric imaging. In the past few years several groups have developed protocols to render tissues “optically transparent” thereby minimising light scatter and allowing inspection of neural networks within intact specimens usually lost in 2D optics.Recently developed tissue clearing methods made it possible to explore intact organs coupling immunohistochemistry in toto withlight-sheet microscopy.
In this talk theory and applications of different tissue-clearing techniques and volume imaging will be presented in the context of Neuroscience to explain how these techniques can be adapted to study the development and organization of the brain as well as of other peripheral organs. Our 3D data demonstrate that with thorough biochemical optimization, we can now detect morphogenetic processes, cell migration and terminal differentiation during embryonic and postnatal development in different species, including humans. These approaches open a novel route for high-resolution studies of brain architecture in mammals in physiological and pathological conditions.
Host: Silvia De Marchis

19/3/21 - Progress report
Brigitta Bonaldo (Group Panzica)
Gestational and lactational exposure to BPA or BPS affects maternal behavior in mice

12/3/21 - Lecture
Lorena Perrone
Université Grenoble Alpes, Grenoble, France

Thioredoxin Interacting Protein and Warburg effect: metabolism driving neurovascular inflammation. Molecular pathways and innovative nanotechnology-based diagnostic.
The major mechanism of cell metabolism reprogramming is defined as the Warburg effect, which consists in a preferential utilization of glucose via glycolysis even in the presence of oxygen. The glucose transporter Glut1 plays a key function in the Warburg effect. Thioredoxin Interacting Protein (TXNIP) is the endogenous inhibitor of the ROS scavenger Thioredoxin (Trx) and also the major regulator of the Glut1 endocytosis. Thus, TXNIP modulates glucose uptake and metabolism.
I will summarize my results showing the different functions of TXNIP in the nervous system. Transient expression of TXNIP is essential for the repair. On the contrary, chronic expression of TXNIP promotes a cascade of cell-specific pathways that ultimately promote neurodegeneration. Notably, silencing of TXNIP prevents in vivo the progression of Diabetic Retinopathy and Alheimer's Disease.
Host: Ferdinando Di Cunto

26/2/21 - Lecture
Daniela Marazziti
Institute of Cell Biology and Neurobiology - CNR, Monterotondo, Roma

GPR37L1: from Bergmann glia to medulloblastoma
In the developing cerebellum, proliferation and differentiation of glial and neuronal cell types depend on the modulation of the sonic hedgehog (Shh) signaling pathway.
The vertebrate G protein-coupled receptor 37-like 1 (Gpr37l1) gene encodes a putative receptor that is expressed in newborn and adult cerebellar Bergmann glia astrocytes. Upon production and characterization of null Gpr37l1 mutant lines, we dissect its functional role in normal and pathological conditions
Host: Annalisa Buffo

19/2/21 - Progress report
Francesca Montarolo (Group Bertolotto)
Gadolinium retention following multiple administrations of  Contrast Agents for magnetic resonance imaging in a Multiple Sclerosis animal model

12/2/21 - Seminar
Elena Parmigiani, PhD
Embryology and Stem Cell Biology - Department of Biomedicine, University of Basel

Notch signaling shapes interferon-gamma response and immune microenvironment in glioma
Gliomas are aggressive brain tumors and a leading cause of cancer mortality, with limited therapeutic options for the patients. Recent advances have highlighted the critical role of the immune tumor microenvironment in regulating cancer progression. The mechanisms controlling tumor-immune cells crosstalk and immune evasion in glioma are not understood, posing a major challenge for the successful implementation of immunomodulatory therapies.  We have recently found that Notch signaling contributes to both cell-autonomous regulation of glioma cell proliferation and paracrine regulation of the tumor microenvironment at multiple levels. Our data indicate that Notch is pivotal in promoting interferon-gamma response and immune surveillance in glioma. Hence, reducing Notch activity levels can be exploited by glioma cells to reinforce immune evasion.
Host: Annalisa Buffo

5/2/21 - Seminar
Paola Barbagallo, PhD 
Nuffield Department of Clinical Neurosciences, University of Oxford
Department of Neuroscience, University of Copenhagen

Dissecting the contribution of dipeptide repeat proteins to the toxicity in C9orf72 mutant iPSC-derived motor neurons from ALS/FTD patients
A large (GGGGCC) repeat expansion in C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS). It causes both loss- and gain-of-function, but the relative contribution of thedifferent mechanisms to the development of ALS remains uncertain. One of the pathomechanisms is the production of dipeptide repeat proteins (PR, PA, GR, GP and GA) via repeat-associated non-ATG translation (DPRs).
Animal and cellular models have suggested that the arginine-rich DPRsare toxic, but C9orf72 patients show that the same DPRs are not very abundant compared to GA, GP and PA. Moreover, the DPR-related phenotypes exhibited in in-vitro models are not always verified in C9orf72 patients.
For these reasons we developed a doxycycline-inducible lentiviral system to regulate DPR expression in induced pluripotent stem cell (iPSC)-derived motor neuron (MN) cultures. The effects of GA and PR expression in CRISPR/Cas9 corrected C9orf72 iPSC-derived MNs were compared to the phenotypes of C9orf72 mutant lines. We found that poly(PR) expression interfered with ER calcium release from IP3R and reduced the maximal mitochondrial respiration. The latest effect may cause deficits to mitochondrial membrane potential, lowering the calcium buffering and enhancing the cellular sensitivity to oxidative stress.
Host: Annalisa Buffo

29/1/21 - Progress report
Roberta Schellino (Group Vercelli)
It's never too late to run a Marathon: a novel biological to sustain muscle innervation and endurance in elderly

Human-induced pluripotent stem cells (hiPSCs) have revolutionized our ability to study human brain diseases, and recent progress in the field is paving the way for improved therapeutics. Here, I will present our optimized processes in generating hiPSC-derived neural progenitors and functional neuronal subtypes populations and how patient-specific hiPSC-derived neural cells can be used to model neuropsychiatric and neurodegenerative diseases.

15/1/21 - Lecture
Federico Forneris (University of Pavia)
Molecular architectures, interactions and functions of neuromuscular synapse organizers

Host: Serena Stanga

8/1/21 - Progress report
Valentina Cerrato (Group Buffo)
Single-cell RNA Sequencing unveils an unprecedented molecular and functional heterogeneity of cerebellar astrocytes

22/1/21 - Lecture
Luciano Conti, Associate Professor of Applied Biology
Dept of Cellular, Computational and Integrated Biology - CIBio, University of Trento, Italy

PSC-based models of neurodegenerative and neuropsychiatric diseases