Publications by authors named "Daniele Linaro"

Inertia is a measure of a power system's capability to counteract frequency disturbances: in conventional power networks, inertia is approximately constant over time, which contributes to network stability. However, as the share of renewable energy sources increases, the inertia associated to synchronous generators declines, which may pose a threat to the overall stability. Reliably estimating the inertia of power systems dominated by inverted-connected sources has therefore become of paramount importance.

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The transformation of synaptic input into action potential output is a fundamental single-cell computation resulting from the complex interaction of distinct cellular morphology and the unique expression profile of ion channels that define the cellular phenotype. Experimental studies aimed at uncovering the mechanisms of the transfer function have led to important insights, yet are limited in scope by technical feasibility, making biophysical simulations an attractive complementary approach to push the boundaries in our understanding of cellular computation. Here we take a data-driven approach by utilizing high-resolution morphological reconstructions and patch-clamp electrophysiology data together with a multi-objective optimization algorithm to build two populations of biophysically detailed models of murine hippocampal CA3 pyramidal neurons based on the two principal cell types that comprise this region.

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How neural circuits develop in the human brain has remained almost impossible to study at the neuronal level. Here, we investigate human cortical neuron development, plasticity, and function using a mouse/human chimera model in which xenotransplanted human cortical pyramidal neurons integrate as single cells into the mouse cortex. Combined neuronal tracing, electrophysiology, and in vivo structural and functional imaging of the transplanted cells reveal a coordinated developmental roadmap recapitulating key milestones of human cortical neuron development.

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Correlated electrical activity in neurons is a prominent characteristic of cortical microcircuits. Despite a growing amount of evidence concerning both spike-count and subthreshold membrane potential pairwise correlations, little is known about how different types of cortical neurons convert correlated inputs into correlated outputs. We studied pyramidal neurons and two classes of GABAergic interneurons of layer 5 in neocortical brain slices obtained from rats of both sexes, and we stimulated them with biophysically realistic correlated inputs, generated using dynamic clamp.

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To support cognitive function, the CA3 region of the hippocampus performs computations involving attractor dynamics. Understanding how cellular and ensemble activities of CA3 neurons enable computation is critical for elucidating the neural correlates of cognition. Here we show that CA3 comprises not only classically described pyramid cells with thorny excrescences, but also includes previously unidentified 'athorny' pyramid cells that lack mossy-fiber input.

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The transplantation of pluripotent stem-cell-derived neurons constitutes a promising avenue for the treatment of several brain diseases. However, their potential for the repair of the cerebral cortex remains unclear, given its complexity and neuronal diversity. Here, we show that human visual cortical cells differentiated from embryonic stem cells can be transplanted and can integrate successfully into the lesioned mouse adult visual cortex.

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Ensembles of cortical neurons can track fast-varying inputs and relay them in their spike trains, far beyond the cut-off imposed by membrane passive electrical properties and mean firing rates. Initially explored in silico and later demonstrated experimentally, investigating how neurons respond to sinusoidally modulated stimuli provides a deeper insight into spike initiation mechanisms and information processing than conventional F-I curve methodologies. Besides net membrane currents, physiological synaptic inputs can also induce a stimulus-dependent modulation of the total membrane conductance, which is not reproduced by standard current-clamp protocols.

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Experimental neuroscience is witnessing an increased interest in the development and application of novel and often complex, closed-loop protocols, where the stimulus applied depends in real-time on the response of the system. Recent applications range from the implementation of virtual reality systems for studying motor responses both in mice and in zebrafish, to control of seizures following cortical stroke using optogenetics. A key advantage of closed-loop techniques resides in the capability of probing higher dimensional properties that are not directly accessible or that depend on multiple variables, such as neuronal excitability and reliability, while at the same time maximizing the experimental throughput.

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Synchronous spiking during cerebellar tasks has been observed across Purkinje cells: however, little is known about the intrinsic cellular mechanisms responsible for its initiation, cessation and stability. The Phase Response Curve (PRC), a simple input-output characterization of single cells, can provide insights into individual and collective properties of neurons and networks, by quantifying the impact of an infinitesimal depolarizing current pulse on the time of occurrence of subsequent action potentials, while a neuron is firing tonically. Recently, the PRC theory applied to cerebellar Purkinje cells revealed that these behave as phase-independent integrators at low firing rates, and switch to a phase-dependent mode at high rates.

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Neuronal firing, synaptic transmission, and its plasticity form the building blocks for processing and storage of information in the brain. It is unknown whether adult human synapses are more efficient in transferring information between neurons than rodent synapses. To test this, we recorded from connected pairs of pyramidal neurons in acute brain slices of adult human and mouse temporal cortex and probed the dynamical properties of use-dependent plasticity.

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Background: Current software tools for electrophysiological experiments are limited in flexibility and rarely offer adequate support for advanced techniques such as dynamic clamp and hybrid experiments, which are therefore limited to laboratories with a significant expertise in neuroinformatics.

New Method: We have developed lcg, a software suite based on a command-line interface (CLI) that allows performing both standard and advanced electrophysiological experiments. Stimulation protocols for classical voltage and current clamp experiments are defined by a concise and flexible meta description that allows representing complex waveforms as a piece-wise parametric decomposition of elementary sub-waveforms, abstracting the stimulation hardware.

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The study of human cortical development has major implications for brain evolution and diseases but has remained elusive due to paucity of experimental models. Here we found that human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), cultured without added morphogens, recapitulate corticogenesis leading to the sequential generation of functional pyramidal neurons of all six layer identities. After transplantation into mouse neonatal brain, human ESC-derived cortical neurons integrated robustly and established specific axonal projections and dendritic patterns corresponding to native cortical neurons.

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Understanding the computational capabilities of the nervous system means to "identify" its emergent multiscale dynamics. For this purpose, we propose a novel model-driven identification procedure and apply it to sparsely connected populations of excitatory integrate-and-fire neurons with spike frequency adaptation (SFA). Our method does not characterize the system from its microscopic elements in a bottom-up fashion, and does not resort to any linearization.

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Stochastic channel gating is the major source of intrinsic neuronal noise whose functional consequences at the microcircuit- and network-levels have been only partly explored. A systematic study of this channel noise in large ensembles of biophysically detailed model neurons calls for the availability of fast numerical methods. In fact, exact techniques employ the microscopic simulation of the random opening and closing of individual ion channels, usually based on Markov models, whose computational loads are prohibitive for next generation massive computer models of the brain.

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This paper provides a global picture of the bifurcation scenario of the Hindmarsh-Rose model. A combination between simulations and numerical continuations is used to unfold the complex bifurcation structure. The bifurcation analysis is carried out by varying two bifurcation parameters and evidence is given that the structure that is found is universal and appears for all combinations of bifurcation parameters.

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