A5004183860- Neural dynamics and brain function
- Neuroscience and Neural Engineering
- Neuroscience and Neuropharmacology Research
- Vestibular and auditory disorders
- Ion channel regulation and function
- Advanced Memory and Neural Computing
- Photoreceptor and optogenetics research
- EEG and Brain-Computer Interfaces
- Electrochemical Analysis and Applications
- 3D Printing in Biomedical Research
- Receptor Mechanisms and Signaling
- Hearing, Cochlea, Tinnitus, Genetics
- Mitochondrial Function and Pathology
- CCD and CMOS Imaging Sensors
- Advanced Fluorescence Microscopy Techniques
- Neuroscience and Music Perception
- Lipid Membrane Structure and Behavior
- Functional Brain Connectivity Studies
- Circadian rhythm and melatonin
- Cell Image Analysis Techniques
- Cancer-related gene regulation
- Neurogenesis and neuroplasticity mechanisms
- Distributed Sensor Networks and Detection Algorithms
- Wnt/β-catenin signaling in development and cancer
- RNA Research and Splicing
University of Milan
2017-2024
Luigi Sacco Hospital
2018-2020
Italian Institute of Technology
2010-2019
Weatherford College
2015
University of Pavia
2001-2010
Istituto Nazionale per la Fisica della Materia
2001
Neurons process information in a highly nonlinear manner, generating oscillations, bursting, and resonance, enhancing responsiveness at preferential frequencies. It has been proposed that slow repolarizing currents could be responsible for both oscillation/burst termination high-pass filtering causes resonance (Hutcheon Yarom, 2000). However, different mechanisms, including electrotonic effects (Mainen Sejinowski, 1996), the expression of resurgent (Raman Bean, 1997), network feedback, may...
Functional connectivity of in vitro neuronal networks was estimated by applying different statistical algorithms on data collected Micro-Electrode Arrays (MEAs). First we tested these "connectivity methods" network models at an increasing level complexity and evaluated the performance terms ROC (Receiver Operating Characteristic) PPC (Positive Precision Curve), a new defined complementary method specifically developed for functional links identification. Then, better actual models, were used...
Abstract To recreate in vitro 3D neuronal circuits will ultimately increase the relevance of results from cultured to whole-brain networks and promote enabling technologies for neuro-engineering applications. Here we fabricate novel elastomeric scaffolds able instruct growth living primary neurons. Such systems allow investigating emerging activity, terms calcium signals, small clusters neurons as a function interplay between 2D or architectures network dynamics. We report ability geometry...
The recent identification of multiple dominant mutations in the gene encoding β-catenin both humans and mice has enabled exploration molecular cellular basis function cognitive impairment. In humans, that cause a spectrum neurodevelopmental disorders have been identified. We identified de novo patients with intellectual disability, carefully characterized their phenotypes, were able to define recognizable disability syndrome. parallel, characterization chemically mutagenized mouse line...
See Lerche (doi:10.1093/brain/awy073) for a scientific commentary on this article.Proline-rich transmembrane protein 2 (PRRT2) is the causative gene heterogeneous group of familial paroxysmal neurological disorders that include seizures with onset in first year life (benign infantile seizures), kinesigenic dyskinesia or combination both. Most PRRT2 mutations are loss-of-function leading to haploinsufficiency and 80% patients carry same frameshift mutation (c.649dupC; p.Arg217Profs*8), which...
The interplay between anatomical connectivity and dynamics in neural networks plays a key role the functional properties of brain associated changes induced by diseases. However, detailed experimental investigation this at both cellular population scales living is limited accessibility. Alternatively, to investigate basic operational principles with morphological, electrophysiological computational methods, activity emerging from large vitro primary neurons organized imposed topologies can...
The recent availability of human induced pluripotent stem cells (hiPSCs) holds great promise as a novel source human-derived neurons for cell and tissue therapies well in vitro drug screenings that might replace the use animal models. However, there is still considerable lack knowledge on functional properties hiPSC-derived neuronal networks, thus limiting their application. Here, upon optimization culture protocols, we demonstrate both spontaneous evoked electrical spiking activities these...
Gephyrin is a key scaffold protein mediating the anchoring of GABAA receptors at inhibitory synapses. Here, we exploited superresolution techniques combined with proximity-based clustering analysis and model simulations to investigate single-molecule gephyrin reorganization during plasticity synapses in mouse hippocampal cultured neurons. This approach revealed that, expression LTP, increase density postsynaptic sites associated promoted formation nanodomains. We demonstrate that...
Long-term potentiation (LTP) is a synaptic change supposed to provide the cellular basis for learning and memory in brain neuronal circuits. Although specific LTP expression mechanisms could be critical determine dynamics of repetitive neurotransmission, this important issue remained largely unexplored. In paper, we have performed whole cell patch-clamp recordings mossy fiber-granule acute rat cerebellar slices studied its computational implications with mathematical model. During LTP,...
Multielectrode arrays (MEAs) are extensively used for electrophysiological studies on brain slices, but the spatial resolution and field of recording conventional limited by low number electrodes available. Here, we present a large-scale array simultaneously from 4096 to study propagating spontaneous evoked network activity in acute murine cortico-hippocampal slices at unprecedented temporal resolution. We demonstrate that multiple chemically induced epileptiform episodes mouse cortex...
In the cerebellum, granule cells are inhibited by Golgi through GABAergic synapses generating complex responses involving both phasic neurotransmitter release and establishment of ambient gamma-aminobutyric acid (GABA) levels. Although at this synapse mechanisms postsynaptic integration have been clarified to a considerable extent, remained largely unknown. Here we investigated quantal properties during repetitive neurotransmission, revealing that tonic GABA(B) receptor activation GABA...
Synapsins (Syn I, Syn II, and III) are a family of synaptic vesicle phosphoproteins regulating transmission plasticity. SYN1/2 genes have been identified as major epilepsy susceptibility in humans synapsin I/II/III triple knockout (TKO) mice epileptic. However, excitatory inhibitory short-term plasticity never analyzed intact neuronal circuits TKO mice. To clarify the generation expression epileptic phenotype, we performed patch-clamp recordings CA1 region acute hippocampal slices from...
A large amount of experimental evidence has highlighted the rapid changes in synaptic efficacy induced by high-frequency stimulation and BDNF at central excitatory synapses. We clarified quantal mechanisms involvement Synapsin I (SynI) phosphorylation expression post-tetanic potentiation (PTP) its modulation mouse glutamatergic autapses. found that PTP is associated with an elevation probability release a concomitant increase size readily releasable pool (RRP). The latter component was...
A nerve cell receives multiple inputs from upstream neurons by way of its synapses. Neuron processing functions are thus influenced changes in the biophysical properties synapse, such as long-term potentiation (LTP) or depression (LTD). This observation has opened new perspectives on basis learning and memory, but quantitative impact information transmission a neuron remains partially elucidated. One major obstacle is high dimensionality neuronal input-output space, which makes it unfeasible...
It has been suggested that imprinted genes are important in the regulation of sleep. However, fundamental question whether genomic imprinting a role sleep remained elusive up to now. In this work we show REM and NREM states differentially modulated by maternally expressed gene Gnas. particular, mice with loss Gnas, complex cognitive processes enhanced while REM-linked behaviors inhibited. This is first demonstration specific overexpression an affects related behavioral traits. Furthermore,...
The complex interplay of multiple molecular mechanisms taking part to synaptic integration is hard disentangle experimentally. Therefore, we developed a biologically realistic computational model based on the rich set data characterizing cerebellar glomerulus microcircuit. A specific issue was determine relative role phasic and tonic inhibition in dynamically regulating granule cell firing, which has not been clarified yet. comprised excitatory mossy fiber-granule inhibitory Golgi...
The lateral mobility of neurotransmitter receptors has been shown to tune synaptic signals. Here we report that GABAA (GABAARs) can diffuse between adjacent dendritic GABAergic synapses in long-living desensitized states, thus laterally spreading "activation memories" inhibitory synapses. Glutamatergic activity limits this inter-synaptic diffusion by trapping GABAARs at excitatory This novel form activity-dependent hetero-synaptic interplay is likely modulate signaling.
Developing neuronal systems intrinsically generate coordinated spontaneous activity that propagates by involving a large number of synchronously firing neurons. In vivo, waves spikes transiently characterize the developing brain circuits and are fundamental for activity-dependent circuit formation. vitro, spiking activity, or network bursts (NBs), interleaved within periods asynchronous emerge during development 2D 3D cultures. Several studies have investigated this type its dynamics, but...
Neurotoxicity and the accumulation of extracellular amyloid-beta1-42 (Aβ) peptides are associated with development Alzheimer's disease (AD) correlate neuronal activity network dysfunctions, ultimately leading to cellular death. However, research on neurodegenerative diseases is hampered by paucity reliable readouts experimental models study such functional decline from an early onset test rescue strategies within networks at resolution. To overcome this important obstacle, we demonstrate a...
Mutations in PRoline-Rich Transmembrane protein 2 (PRRT2) underlie a group of paroxysmal disorders including epilepsy, kinesigenic dyskinesia and migraine. Most the mutations lead to impaired PRRT2 expression and/or function, emphasizing pathogenic role deficiency. In this work, we investigated phenotype primary hippocampal neurons obtained from mouse embryos which gene was constitutively inactivated. Although is expressed by both excitatory inhibitory neurons, its deletion decreases number...
Based on experiments performed with high-resolution Active Pixel Sensor microelectrode arrays (APS-MEAs) coupled spontaneously active hippocampal cultures, this work investigates the spatial resolution effects of neuroelectronic interface analysis recorded electrophysiological signals. The adopted methodology consists, first, in recording spontaneous activity at highest (interelectrode separation 21 mum) from whole array 4096 microelectrodes. Then, full dataset is spatially downsampled order...
Despite many structural and functional aspects of the brain organization have been extensively studied in neuroscience, we are still far from a clear understanding intricate structure-function interactions occurring multi-layered architecture, where billions different neurons involved. Although structure function can individually convey large amount information, only combined study these two probably shade light on how circuits develop operate at cellular scale. Here, propose novel approach...