Neocortical Layer 4 to Layer 2/3 Sensory Information Processing Investigated with Digital-Light-Projection Neuronal Photostimulation

The mammalian brain forms neuronal networks and microcircuits with cell-type- and anatomical-specific synaptic connections. Despite great advances in elucidating the cellular physiology of the nervous system, little is known about the computational processes occurring at the level of neuronal microcircuits. Much success has been reported in describing the synaptic input patterns of many brain regions and cell types using photostimulation systems; however, these systems are severely limited in their ability to study the integration of synaptic input from multiple synchronous or temporally correlated presynaptic locations. Here we describe a system that allows the generation of arbitrary 2-D stimulus patterns with thousands of independently controlled sites to manipulate the activity of populations of neurons with high spatial and temporal precision. The PC-controlled Digital-Light-Processing (DLP) based system updates the 780,000 parallel photostimulation beams, or pixels, at a maximum rate of 13 kHz. With the currently used projection objective, the pixel sizes at the plane of focus are 7.3 µm2 . The high-power UV laser source used in this system provides a light flux density sufficient for bins of 8x8 pixels (21.6 µm x 21.6 µm) with dwell times as low 3 ms to reliably induce action potentials in 2.5 mM MNI-caged glutamate. At these settings the effective diameter of a glutamate uncaging site is \u3c 86 µm, which is equivalent to most other UV photostimulation rigs. With DLP photostimulation, sub-threshold responses and action potentials can be synchronously induced at thousands of sites over a 2.76 mm x 2.07 mm area, a capability unmatched by any other current system. This DLP-based system has the unique capability to investigate normal and diseased circuit properties by investigating neuronal responses to spatiotemporally complex activity patterns. This technique was used to investigate the temporal integration of synaptic input in the whisker barrel cortex of mice. The neocortex is organized into layers, with neuronal networks and circuits formed by layer-specific connections. While the anatomical organization of these circuits has been well characterized, the information processing and coding performed by these ensembles is poorly understood. A key component of this investigation concerns the transmission and transformation of the neuronal representation from one neuronal pool to the next. In the rodent somatosensory barrel cortex, histologically-distinguishable “barrels” in layer 4 (L4) receive principal input from a single whisker. L4 projects to layer II/III (L2/3), where the circuit diverges to multiple postsynaptic targets. Using the DLP-photostimulation system, we modulated the synchronicity of action potentials in L4 cells while recording from L2/3 in an acute slice preparation. This data shows that synchronous activity in L4 neurons is highly effective at eliciting strong spiking responses in L2/3 pyramidal cells, while asynchronous L4 activity fails to drive L2/3 to action-potential threshold. Pharmacological manipulation of the slice-bathing solution has suggested that this phenomenon is AMPA-receptor dependent and modulated by NMDA receptor activity. Intracellular pharmacological manipulations suggest that postsynaptic conductances also play a role in the nonlinear L2/3 synaptic integration of L4 activity

Underlying Mechanisms of Epilepsy

This book is a very provocative and interesting addition to the literature on Epilepsy. It offers a lot of appealing and stimulating work to offer food of thought to the readers from different disciplines. Around 5% of the total world population have seizures but only 0.9% is diagnosed with epilepsy, so it is very important to understand the differences between seizures and epilepsy, and also to identify the factors responsible for its etiology so as to have more effective therapeutic regime. In this book we have twenty chapters ranging from causes and underlying mechanisms to the treatment and side effects of epilepsy. This book contains a variety of chapters which will stimulate the readers to think about the complex interplay of epigenetics and epilepsy

The protonic brain: engineering a simple brain emulator and investigating physical mechanisms in non-local communication

The brain is not entirely as it has been described in the classic neuroscientific literature. Physical and chemical properties of brain function can be separated from classical brain structure, allowing for multiple realizations of memory processing and the expression of correlates of consciousness. Further, the brain can be described as energy or information separate from although related to the organic structure which is perhaps subject to technologies which facilitate non-local transfer of data. Chapter 1 introduces the subject and provides sufficient information to explore the major concepts outlined in later sections. Chapter 2 outlines an experimental demonstration of electrophysiological activity in an abiological material which strongly correlates with human quantitative electroencephalographic (QEEG) frequency spectra under specified geometrical and chemical constraints. In Chapter 3, results indicate that this same amorphous material can effectively store and release information when classically conditioned, indicating learning and network formation can be separated from cells proper. Chapter 4 presents a technology which can effectively link two simple chemical systems such that equal and opposite reactions are induced at locus A upon elicitation of a given event within locus B. Chapter 5 provides a systematic analysis of the electromagnetic field dynamics associated with the aforementioned technology, providing both experimental and theoretical grounding. Chapter 6 is a general discussion which links these concepts and provides a summary of the works as they relate to the protonic brain.Master's These

Physiological role of PRRT2 and its involvement in the pathogenesis of paroxysmal disorders

Mutations in the PRoline-Rich Transmembrane protein 2 gene (PRRT2) underlie a heterogeneous group of paroxysmal disorders encompassing infantile epilepsy, paroxysmal kinesigenic dyskinesia, a combination of these phenotypes and migraine. For the majority of the pathogenic PRRT2 variants, the mutant proteins are not expressed or not correctly targeted to the plasma membrane, resulting in a loss-of function mechanism for PRRT2-related diseases. PRRT2 is a neuron-specific, type II transmembrane protein of 340 amino acids with an important functional role in synapse formation and maintenance, as well as in the regulation of fast neurotransmitter release at both glutamatergic and GABAergic terminals. The PRRT2 knock-out (PRRT2-KO) mouse, in which PRRT2 has been constitutively inactivated, displays alterations in brain structure and a sharp paroxysmal phenotype, reminiscent of the most common clinical manifestations of the human PRRT2-linked diseases. To gain further insights on the pathogenic role of PRRT2 deficiency, I used Multi-Electrode Arrays (MEAs) to characterize neuronal activity generated by primary hippocampal cultures obtained from the PRRT2-KO mouse embryos and to assess the epileptic propensity of cortico-hippocampal slices obtained from the same animal model. This experimental approach revealed a state of heightened spontaneous activity, hyper-synchronization in population bursts of action potentials (APs) and enhanced responsiveness to external stimuli in mutant networks. A complex interplay between (i) a synaptic phenotype, with weakened spontaneous transmission and increased short-term facilitation, and (ii) a marked increase in intrinsic excitability of excitatory neurons as assessed by single-cell electrophysiology, upholds this network phenotype. Furthermore, our group has generated cortical neurons from induced pluripotent stem cells (iPSCs) derived from heterozygous and homozygous siblings carrying the most common C.649dupC mutation. Patch-clamp recordings in neurons from homozygous patients showed an increased Na+ current that was fully rescued by expression of exogenous wild-type PRRT2. A strikingly similar electrophysiological phenotype was observed in excitatory primary cortical neurons from the PRRT2-KO mouse, which was accompanied by an increased length of the axon initial segment (AIS). At the network level, mutant cortical neurons grown on MEAs also displayed a state of spontaneous and evoked hyper-excitability and elevated propensity to synchronize their activity in network bursting events

Special Topics in Information Technology

This open access book presents thirteen outstanding doctoral dissertations in Information Technology from the Department of Electronics, Information and Bioengineering, Politecnico di Milano, Italy. Information Technology has always been highly interdisciplinary, as many aspects have to be considered in IT systems. The doctoral studies program in IT at Politecnico di Milano emphasizes this interdisciplinary nature, which is becoming more and more important in recent technological advances, in collaborative projects, and in the education of young researchers. Accordingly, the focus of advanced research is on pursuing a rigorous approach to specific research topics starting from a broad background in various areas of Information Technology, especially Computer Science and Engineering, Electronics, Systems and Control, and Telecommunications. Each year, more than 50 PhDs graduate from the program. This book gathers the outcomes of the thirteen best theses defended in 2020-21 and selected for the IT PhD Award. Each of the authors provides a chapter summarizing his/her findings, including an introduction, description of methods, main achievements and future work on the topic. Hence, the book provides a cutting-edge overview of the latest research trends in Information Technology at Politecnico di Milano, presented in an easy-to-read format that will also appeal to non-specialists

PASSIVE THERMAL CONTROL SYSTEMS FOR SPACE INSTRUMENTS MAKING – SCIENTIFIC BACKGROUND, QUALIFICATION, EXPLOITATION IN SPACE

Passive thermal control systems (TCS) are one of obligatory system of any space mission, used as on large spacecraft and microsatellites Supporting of required temperature range for space instruments is supported by rational design of TCS with optimal choice of main thermal control components such as multilayer insulation, optical coatings, heat conductive elements, heat insulation supports, thermal conductive gaskets, radiating surfaces and other elements. New ideology in TCS design has come after appearance of new element – heat pipe(s) which is a super heat conductive thermal conductor with constant or variable thermal properties

Special Topics in Information Technology

This open access book presents thirteen outstanding doctoral dissertations in Information Technology from the Department of Electronics, Information and Bioengineering, Politecnico di Milano, Italy. Information Technology has always been highly interdisciplinary, as many aspects have to be considered in IT systems. The doctoral studies program in IT at Politecnico di Milano emphasizes this interdisciplinary nature, which is becoming more and more important in recent technological advances, in collaborative projects, and in the education of young researchers. Accordingly, the focus of advanced research is on pursuing a rigorous approach to specific research topics starting from a broad background in various areas of Information Technology, especially Computer Science and Engineering, Electronics, Systems and Control, and Telecommunications. Each year, more than 50 PhDs graduate from the program. This book gathers the outcomes of the thirteen best theses defended in 2020-21 and selected for the IT PhD Award. Each of the authors provides a chapter summarizing his/her findings, including an introduction, description of methods, main achievements and future work on the topic. Hence, the book provides a cutting-edge overview of the latest research trends in Information Technology at Politecnico di Milano, presented in an easy-to-read format that will also appeal to non-specialists

Mathematical Modelling of the Neurochemical Processes in Schizophrenia

Schizophrenia is an endogenous psychosis with a 1 \% prevalence in world population. Several pharmacological studies suggest that alterations in the function of different neurotransmitter systems such as dopamine or glutamate are related to schizophrenic symptoms. This thesis represents mathematical models that are constructed to investigate the dynamical behaviour of the neurochemical systems in the human brain. These models formulate the anatomical properties and physiological processes of synapses, single brain compartments and large neurochemical pathways involved in the regulation of behaviour such as the basal ganglia and the limbic system. The interaction between the neurochemical systems and the electrophysiological activities are considered by modelling in different scales. In the synaptic scale, it has been shown that the transport of neurotransmitters in the synaptic cleft is merely governed by electrical forces than diffusion. The intra-synaptic concentration of neurotransmitters is modelled using partial differential equations and is coupled to the Hodgkin-Huxley equation (neurochemical modification) to model the effect of neurotransmitter-receptor binding in the generation of post-synaptic potentials. Considering the morphological and ultra-morphological studies of brain compartments, the averaged electrophysiological activity is modelled by integral equations respecting these internal structures. A system comprised by nonlinear delay differential equations is constructed to simulate the dynamical behaviour of neurochemical concentrations, coupled to the local electrophysiological activity of the compartments, on the brain pathways. By parameter sensitivity analysis, we have also investigated qualitatively the influence of certain anti-psychotic agents. Synchronized oscillations are experienced in electrophysiological systems. The neurotransmitter concentrations also demonstrate an oscillatory behaviour. The resulting oscillatory dynamics of these processes reveals a profound view on the relation between the dynamical behaviour of the neurochemical systems and the occurrence of psychotic states. These facts led us to establish a hypothesis on this relation, called the oscillation hypothesis of psychosis. Because of the general formulation of the models, these are not only useful for schizophrenia, but also for the investigations of other neurological diseases