Cortical region interactions and the functional role of apical dendrites

The basal and distal apical dendrites of pyramidal cells occupy distinct cortical layers and are targeted by axons originating in different cortical regions. Hence, apical and basal dendrites receive information from distinct sources. Physiological evidence suggests that this anatomically observed segregation of input sources may have functional significance. This possibility has been explored in various connectionist models that employ neurons with functionally distinct apical and basal compartments. A neuron in which separate sets of inputs can be integrated independently has the potential to operate in a variety of ways which are not possible for the conventional model of a neuron in which all inputs are treated equally. This article thus considers how functionally distinct apical and basal dendrites can contribute to the information processing capacities of single neurons and, in particular, how information from different cortical regions could have disparate affects on neural activity and learning

29th Annual Computational Neuroscience Meeting: CNS*2020

Meeting abstracts This publication was funded by OCNS. The Supplement Editors declare that they have no competing interests. Virtual | 18-22 July 202

The Performance of Associative Memory Models with Biologically Inspired Connectivity

This thesis is concerned with one important question in artificial neural networks, that is, how biologically inspired connectivity of a network affects its associative memory performance. In recent years, research on the mammalian cerebral cortex, which has the main responsibility for the associative memory function in the brains, suggests that the connectivity of this cortical network is far from fully connected, which is commonly assumed in traditional associative memory models. It is found to be a sparse network with interesting connectivity characteristics such as the “small world network” characteristics, represented by short Mean Path Length, high Clustering Coefficient, and high Global and Local Efficiency. Most of the networks in this thesis are therefore sparsely connected. There is, however, no conclusive evidence of how these different connectivity characteristics affect the associative memory performance of a network. This thesis addresses this question using networks with different types of connectivity, which are inspired from biological evidences. The findings of this programme are unexpected and important. Results show that the performance of a non-spiking associative memory model is found to be predicted by its linear correlation with the Clustering Coefficient of the network, regardless of the detailed connectivity patterns. This is particularly important because the Clustering Coefficient is a static measure of one aspect of connectivity, whilst the associative memory performance reflects the result of a complex dynamic process. On the other hand, this research reveals that improvements in the performance of a network do not necessarily directly rely on an increase in the network’s wiring cost. Therefore it is possible to construct networks with high associative memory performance but relatively low wiring cost. Particularly, Gaussian distributed connectivity in a network is found to achieve the best performance with the lowest wiring cost, in all examined connectivity models. Our results from this programme also suggest that a modular network with an appropriate configuration of Gaussian distributed connectivity, both internal to each module and across modules, can perform nearly as well as the Gaussian distributed non-modular network. Finally, a comparison between non-spiking and spiking associative memory models suggests that in terms of associative memory performance, the implication of connectivity seems to transcend the details of the actual neural models, that is, whether they are spiking or non-spiking neurons

Brain Computations and Connectivity [2nd edition]

This is an open access title available under the terms of a CC BY-NC-ND 4.0 International licence. It is free to read on the Oxford Academic platform and offered as a free PDF download from OUP and selected open access locations. Brain Computations and Connectivity is about how the brain works. In order to understand this, it is essential to know what is computed by different brain systems; and how the computations are performed. The aim of this book is to elucidate what is computed in different brain systems; and to describe current biologically plausible computational approaches and models of how each of these brain systems computes. Understanding the brain in this way has enormous potential for understanding ourselves better in health and in disease. Potential applications of this understanding are to the treatment of the brain in disease; and to artificial intelligence which will benefit from knowledge of how the brain performs many of its extraordinarily impressive functions. This book is pioneering in taking this approach to brain function: to consider what is computed by many of our brain systems; and how it is computed, and updates by much new evidence including the connectivity of the human brain the earlier book: Rolls (2021) Brain Computations: What and How, Oxford University Press. Brain Computations and Connectivity will be of interest to all scientists interested in brain function and how the brain works, whether they are from neuroscience, or from medical sciences including neurology and psychiatry, or from the area of computational science including machine learning and artificial intelligence, or from areas such as theoretical physics

Evolutionary engineering of green fluorescent protein calcium biosensors

Neurobiology continues to be one of the great frontiers in biological sciences. The number of neurons in the brain, and the complex neuronal circuits they constitute, will keep scientists trying to decipher them challenged for years to come. In the last decade, the use of genetically encoded calcium indicators (GECIs) to monitor and visualize neuronal activity has greatly advanced. Calcium imaging using GECIs has become a principal modality to elucidate neuronal coding and signaling processes. GECIs provide clear advantages over synthetic calcium dyes by enabling long-term expression and chronic imaging in targeted neurons in vivo. Whilst most improvements of GECIs have been primarily focusing on faster kinetics, calcium sensitivity, brightness and signal strength; less attention has been on GECIs’ likely impact on cellular environments via calcium buffering. Studies have shown that long-term expression of GECIs at high intracellular concentrations can lead to pathological changes and reduced responsiveness in cells. The objective of this dissertation was to design a new family of GECIs suitable for long-term monitoring of neuronal calcium activity. In contrast to previous optimization strategies, here a new species of calcium binding protein, troponin C from Opsanus tau, was used as a basis for the development of a minimal calcium-binding domain. The minimal domain was fused to brighter fluorescent proteins to generate novel GECIs with improved properties. Consequently, the novel GECIs were optimized through iterative rounds of directed molecular evolution and screening, resulting in the Twitch-family of GECIs. In Chapter 2, we describe the structure-function relationships of a previously published FRET-based calcium indicator, the TN-XXL. The structure-function relationship in FRET- based GECIs is largely uncharacterized due to the artificial and multi-modular composition. By utilizing a combination of protein engineering, spectroscopic and biophysical analyses, we show that two of the four calcium binding sites dominate the FRET output. Furthermore, we found that local conformational changes of these sites match the kinetics of FRET change. We show that TN-XXL changes from a flexible elongated structure to a rigid globular shape upon binding calcium. The insights gained from this work formed the basis for the engineering of the FRET-based GECIs described in this work. In Chapter 3, a newly developed minimal domain FRET-based GECI, Twitch-1CD, was introduced into auto-antigen-specific and non–auto-antigen-specific CD4+ T cells. We demonstrated for the first time in vivo how a GECI is fully expressed in T cells, and thus allowing for detailed recording and visualization of calcium signaling during T cell antigen- recognition. In Chapter 4, we orchestrated the evolution of the Twitch-family of GECIs, with better signal- to-noise ratios (SNR), greater dynamic range (∆R/R) and calcium kinetics. These indicators underwent rational design and directed molecular evolution, followed by bacterial plate screening and a fluorescent imaging screening assay in hippocampal neurons. The novel GECIs were subsequently applied in a series of studies, emphasizing their improvements to previous FRET-based GECIs

Assembly and post-assembly manipulation of polyelectrolyte multilayers for control of bacterial attachment and viability

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2009.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Includes bibliographical references (p. 123-136).The overall goal of this thesis was to exploit the versatility of the polyelectrolyte multilayer (PEM) platform to consider bacteria-substrata interactions by varying multilayer assembly and post-assembly conditions. We developed multiple PEM systems to probe the ability of substrata to resist bacteria attachment or act as contact-killing antimicrobials. In the first study, by varying the pH of assembly, we developed PEMs of identical chemical composition (polyallylamine hydrochloride (PAH) and polyacrylic acid (PAA)) with distinct mechanical moduli (1-100 MPa). Once characterized, these PEMs showed that, under certain conditions, bacterial attachment correlated with increasing modulus. Thus, substrata stiffness was found to be an additional parameter to consider when studying bacterial attachment. The next project focused on PEMs of PAH and poly(sodium-4-styrene sulfonate) (SPS) assembled at high pH that showed a reversible swelling transition upon immersion in a low pH solution. These acid-treated PEMs presented high positive charge density and mobility, and were capable of killing bacteria on contact. SPS/PAH PEMs were used as a model system to enumerate the design parameters that should be considered to create a cationic killing surface. A third PEM system was employed to further illustrate the effects of multilayer assembly and post-assembly conditions on bacteria. Cross-linked hydrogen-bonded PAA and poly(acrylamide) (PAAm) multilayers were modified post-assembly by the adsorption of PAH at various pH values. These multilayers underwent a variety of morphological transitions depending on the pH of PAH adsorption. At mid-range pH values, the film stiffened and promoted aqueous bacterial attachment.(cont.) At high pH values, PAH adsorbed onto the surface with many unbound uncharged amine groups. When the multilayer was exposed to physiological pH values for bacteria assays, the amine groups became protonated and participated in a cationic-killing effect. Finally, biofilm control was examined by investigating initial biofilm formation on films of various mechanical stiffness and surface charge. No differences were visible via optical microscopy. An alternative approach to biofilm control was considered whereby a dissociating multilayer region lifted-off a contaminated layer, exposing a clean, unfouled underlying surface.by Jenny A. Lichter.Ph.D

Active Materials

What is an active material? This book aims to redefine perceptions of the materials that respond to their environment. Through the theory of the structure and functionality of materials found in nature a scientific approach to active materials is first identified. Further interviews with experts from the natural sciences and humanities then seeks to question and redefine this view of materials to create a new definition of active materials

Active Materials

What is an active material? This book aims to redefine perceptions of the materials that respond to their environment. Through the theory of the structure and functionality of materials found in nature a scientific approach to active materials is first identified. Further interviews with experts from the natural sciences and humanities then seeks to question and redefine this view of materials to create a new definition of active materials

Into Complexity. A Pattern-oriented Approach to Stakeholder Communities

The NWO-programme ”the societal aspects of genomics”, has called for stronger means of collaboration and deliberative involvement between the various stakeholders of genomics research. Within the project group assembled at the University for Humanistics, this call was translated to the ‘lingua democratica’, in which the prerequisites of such deliberative efforts were put to scrutiny. The contribution of this thesis has taken a more or less abstract angle to this task, and sought to develop a vocabulary that can be shared amongst various stakeholders with different backgrounds, interests and stakes for any complex theme, although genomics has more or less been in focus throughout the research. As ‘complexity thinking’ is currently a theme in both the ‘hard’ sciences as the social sciences and the humanities, and has always been an issue for professionals, this concept was pivotal in achieving such an inclusive angle. However, in order to prevent that complexity would become fragmented due to disciplinary boundaries, it is essential that those aspects of complexity that seem to return in many discussions would be made clear, and stand out with respect to the complexities of specialisation. The thesis has argued that the concept of ‘patterns’ applies for these aspects, and they form the backbone of the vocabulary that has been developed. Especially patterns of feedback have been given much attention, as this concept is pivotal for many complex themes. However, although patterns are implicitly or explicitly used in many areas, there is little methodological (and philosophical) underpinning of what they are and why they are able to do what they do. As a result, quite some attention has been given to these issues, and how they relate to concepts such as ‘information’,‘order’ and complexity itself. From these explorations, the actual vocabulary was developed, including the methodological means to use this vocabulary. This has taken the shape of a recursive development of a so-called pattern-library, which has crossed disciplinary boundaries, from technological areas, through biology, psychology and the social sciences, to a topic that is typical of the humanities. This journey across the divide of C.P. Snow’s ‘two cultures’ is both a test for a lingua democratica, as well as aimed to demonstrate how delicate, and balanced such a path must be in order to be effective, especially if one aims to retain certain coherence along the way. Finally, the methodology has been applied in a very practical way, to a current development that hinges strongly on research in genomics, which is trans-humanist movement