The function of NaV1.8 clusters in lipid rafts

NaV1.8 is a voltage gated sodium channel mainly expressed on the membrane of thin diameter c-fibre neurons involved in the transmission of pain signals. In these neurons NaV1.8 is essential for the propagation of action potentials. NaV1.8 is located in lipid rafts along the axons of sensory neurons and disruption of these lipid rafts leads to NaV1.8 dependant conduction failure. Using computational modelling, I show that the clustering of NaV1.8 channels in lipid rafts along the axon of thin diameter neurons is energetically advantageous and requires fewer channels to conduct action potentials. During an action potential NaV1.8 currents across the membrane in these thin axons are large enough to dramatically change the sodium ion concentration gradient and thereby void the assumptions upon which the cable equation is based. Using scanning electron microscopy NaV1.8 is seen to be clustered, as are lipid raft marker proteins, on neurites at scales below 200nm. FRET signals show that the lipid raft marker protein Flotillin is densely packed on the membrane however disruption of rafts does not reduce the FRET signal from dense protein packing. Using mass spectrometry I investigated the population of proteins found in the lipid rafts of sensory neurons. I found that the membrane pump NaK-ATPase, which restores the ion concentrations across the membrane, is also contained in lipid rafts. NaK-ATPase may help to offset concentration changes due to NaV1.8 currents enabling the repeated firing of c-fibres, which is associated with spontaneous pain in chronic pain disorders.Open Acces

Real-time Neuromorphic Visual Pre-Processing and Dynamic Saliency

The human brain is by far the most computationally complex, efficient, and reliable computing system operating under such low-power, small-size, and light-weight specifications. Within the field of neuromorphic engineering, we seek to design systems with facsimiles to that of the human brain with means to reach its desirable properties. In this doctoral work, the focus is within the realm of vision, specifically visual saliency and related visual tasks with bio-inspired, real-time processing. The human visual system, from the retina through the visual cortical hierarchy, is responsible for extracting visual information and processing this information, forming our visual perception. This visual information is transmitted through these various layers of the visual system via spikes (or action potentials), representing information in the temporal domain. The objective is to exploit this neurological communication protocol and functionality within the systems we design. This approach is essential for the advancement of autonomous, mobile agents (i.e. drones/MAVs, cars) which must perform visual tasks under size and power constraints in which traditional CPU or GPU implementations to not suffice. Although the high-level objective is to design a complete visual processor with direct physical and functional correlates to the human visual system, we focus on three specific tasks. The first focus of this thesis is the integration of motion into a biologically-plausible proto-object-based visual saliency model. Laurent Itti, one of the pioneers in the field, defines visual saliency as ``the distinct subjective perceptual quality which makes some items in the world stand out from their neighbors and immediately grab our attention.'' From humans to insects, visual saliency is important for the extraction of only interesting regions of visual stimuli for further processing. Prior to this doctoral work, Russel et al. \cite{russell2014model} designed a model of proto-object-based visual saliency with biological correlates. This model was designed for computing saliency only on static images. However, motion is a naturally occurring phenomena that plays an essential role in both human and animal visual processing. Henceforth, the most ideal model of visual saliency should consider motion that may be exhibited within the visual scene. In this work a novel dynamic proto-object-based visual saliency is described which extends the Russel et. al. saliency model to consider not only static, but also temporal information. This model was validated by using metrics for determining how accurate the model is in predicting human eye fixations and saccades on a public dataset of videos with attached eye tracking data. This model outperformed other state-of-the-art visual saliency models in computing dynamic visual saliency. Such a model that can accurately predict where humans look, can serve as a front-end component to other visual processors performing tasks such as object detection and recognition, or object tracking. In doing so it can reduce throughput and increase processing speed for such tasks. Furthermore, it has more obvious applications in artificial intelligence in mimicking the functionality of the human visual system. The second focus of this thesis is the implementation of this visual saliency model on an FPGA (Field Programmable Gate Array) for real-time processing. Initially, this model was designed within MATLAB, a software-based approach running on a CPU, which limits the processing speed and consumes unnecessary amounts of power due to overhead. This is detrimental for integration with an autonomous, mobile system which must operate in real-time. This novel FPGA implementation allows for a low-power, high-speed approach to computing visual saliency. There are a few existing FPGA-based implementations of visual saliency, and of those, none are based on the notion of proto-objects. This work presents the first, to our knowledge, FPGA implementation of an object-based visual saliency model. Such an FPGA implementation allows for the low-power, light-weight, and small-size specifications that we seek within the field of neuromorphic engineering. For validating the FPGA model, the same metrics are used for determining the extent to which it predicts human eye saccades and fixations. We compare this hardware implementation to the software model for validation. The third focus of this thesis is the design of a generic neuromorphic platform both on FPGA and VLSI (Very-Large-Scale-Integration) technology for performing visual tasks, including those necessary in the computation of the visual saliency. Visual processing tasks such as image filtering and image dewarping are demonstrated via this novel neuromorphic technology consisting of an array of hardware-based generalized integrate-and-fire neurons. It allows the visual saliency model's computation to be offloaded onto this hardware-based architecture. We first demonstrate an emulation of this neuromorphic system on FPGA demonstrating its capability of dewarping and filtering tasks as well as integration with a neuromorphic camera called the ATIS (Asynchronous Time-based Image Sensor). We then demonstrate the neuromorphic platform implemented in CMOS technology, specifically designed for low-mismatch, high-density, and low-power. Such a VLSI technology-based platform further bridges the gap between engineering and biology and moves us closer towards developing a complete neuromorphic visual processor

Learning and Decision Making in Social Contexts: Neural and Computational Models

Social interaction is one of humanity's defining features. Through it, we develop ideas, express emotions, and form relationships. In this thesis, we explore the topic of social cognition by building biologically-plausible computational models of learning and decision making. Our goal is to develop mechanistic explanations for how the brain performs a variety of social tasks, to test those theories by simulating neural networks, and to validate our models by comparing to human and animal data. We begin by introducing social cognition from functional and anatomical perspectives, then present the Neural Engineering Framework, which we use throughout the thesis to specify functional brain models. Over the course of four chapters, we investigate many aspects of social cognition using these models. We begin by studying fear conditioning using an anatomically accurate model of the amygdala. We validate this model by comparing the response properties of our simulated neurons with real amygdala neurons, showing that simulated behavior is consistent with animal data, and exploring how simulated fear generalization relates to normal and anxious humans. Next, we show that biologically-detailed networks may realize cognitive operations that are essential for social cognition. We validate this approach by constructing a working memory network from multi-compartment cells and conductance-based synapses, then show that its mnemonic performance is comparable to animals performing a delayed match-to-sample task. In the next chapter, we study decision making and the tradeoffs between speed and accuracy: our network gathers information from the environment and tracks the value of choice alternatives, making a decision once certain criteria are met. We apply this model to a two-choice decision task, fit model parameters to recreate the behavior of individual humans, and reproduce the speed-accuracy tradeoff evident in the human population. Finally, we combine our networks for learning, working memory, and decision making into a cognitive agent that uses reinforcement learning to play a simple social game. We compare this model with two other cognitive architectures and with human data from an experiment we ran, and show that our three cognitive agents recreate important patterns in the human data, especially those related to social value orientation and cooperative behavior. Our concluding chapter summarizes our contributions to the field of social cognition and proposes directions for further research. The main contribution of this thesis is the demonstration that a diverse set of social cognitive abilities may be explained, simulated, and validated using a functionally-descriptive, biologically-plausible theoretical framework. Our models lay a foundation for studying increasingly-sophisticated forms of social cognition in future work

Dynamical systems techniques in the analysis of neural systems

As we strive to understand the mechanisms underlying neural computation, mathematical models are increasingly being used as a counterpart to biological experimentation. Alongside building such models, there is a need for mathematical techniques to be developed to examine the often complex behaviour that can arise from even the simplest models. There are now a plethora of mathematical models to describe activity at the single neuron level, ranging from one-dimensional, phenomenological ones, to complex biophysical models with large numbers of state variables. Network models present even more of a challenge, as rich patterns of behaviour can arise due to the coupling alone. We first analyse a planar integrate-and-fire model in a piecewise-linear regime. We advocate using piecewise-linear models as caricatures of nonlinear models, owing to the fact that explicit solutions can be found in the former. Through the use of explicit solutions that are available to us, we categorise the model in terms of its bifurcation structure, noting that the non-smooth dynamics involving the reset mechanism give rise to mathematically interesting behaviour. We highlight the pitfalls in using techniques for smooth dynamical systems in the study of non-smooth models, and show how these can be overcome using non-smooth analysis. Following this, we shift our focus onto the use of phase reduction techniques in the analysis of neural oscillators. We begin by presenting concrete examples showcasing where these techniques fail to capture dynamics of the full system for both deterministic and stochastic forcing. To overcome these failures, we derive new coordinate systems which include some notion of distance from the underlying limit cycle. With these coordinates, we are able to capture the effect of phase space structures away from the limit cycle, and we go on to show how they can be used to explain complex behaviour in typical oscillatory neuron models

Dynamical systems techniques in the analysis of neural systems

As we strive to understand the mechanisms underlying neural computation, mathematical models are increasingly being used as a counterpart to biological experimentation. Alongside building such models, there is a need for mathematical techniques to be developed to examine the often complex behaviour that can arise from even the simplest models. There are now a plethora of mathematical models to describe activity at the single neuron level, ranging from one-dimensional, phenomenological ones, to complex biophysical models with large numbers of state variables. Network models present even more of a challenge, as rich patterns of behaviour can arise due to the coupling alone. We first analyse a planar integrate-and-fire model in a piecewise-linear regime. We advocate using piecewise-linear models as caricatures of nonlinear models, owing to the fact that explicit solutions can be found in the former. Through the use of explicit solutions that are available to us, we categorise the model in terms of its bifurcation structure, noting that the non-smooth dynamics involving the reset mechanism give rise to mathematically interesting behaviour. We highlight the pitfalls in using techniques for smooth dynamical systems in the study of non-smooth models, and show how these can be overcome using non-smooth analysis. Following this, we shift our focus onto the use of phase reduction techniques in the analysis of neural oscillators. We begin by presenting concrete examples showcasing where these techniques fail to capture dynamics of the full system for both deterministic and stochastic forcing. To overcome these failures, we derive new coordinate systems which include some notion of distance from the underlying limit cycle. With these coordinates, we are able to capture the effect of phase space structures away from the limit cycle, and we go on to show how they can be used to explain complex behaviour in typical oscillatory neuron models

Biomimetic models of visual navigation - active sensing for embodied intelligence

Insects have developed small scale search behaviours to pursue navigation relevant stimuli more effectively. These often resemble a variation of Zig-Zagging, steering periodically to the left and right, therefore increasing the sampling. In this context we investigate the role of a homologous insect brain structure, the Lateral Accessory Lobe (LAL), which has been described as a pre-motor centre but received limited attention so far. Following a synthesis of the literature on the LAL we developed a steering framework, which proposes that with lateralised stimuli as input, the LAL can initiate a Zig-Zagging behaviour if the input is too weak, meaning unreliable, and targeted steering behaviours if the input is strong, thus reliable. Based on this framework we model a Spiking Neural Network (SNN) investigating a sensory modulated Central Pattern Generator (CPG) as a possible neural mechanism enabling adaptive search behaviours. We investigated the parameter space of the model to discover both the range of possible behaviours as well as which parameter combinations lead to the previously described behaviour. We found that no parameter combination accounts for the majority of observed behaviours. Furthermore, changing the computational noise levels does not lead to break-down of this behaviour. We conclude, that this neural architecture is robust to generate an adaptable Zig-Zagging behaviour. Additionally, we developed a more comprehensive network to explore the functions of known neuron-types with regard to motor control. To investigate how this steering framework might work for view based navigation, we investigated how lateralised sensory input can be used for snapshot navigation. We used a 3D-reconstruction from a LiDAR-scanned field-site (“Antworld”) to generate realistic visual stimuli. Instead of using the entire panorama, we subdivided this into two Fields of View for snapshot generation and the later image comparisons. The difference of image familiarity from both sides was subtracted to initiate a steering response into the most familiar direction. We found that a bigger Field of View alongside non-forward facing memories generated the most correct steering responses towards the snapshot direction. This demonstrates that the LAL-inspired steering framework can be functional for a complex sensori-motor task that had previously not been implicated in LAL functionality. Finally, we modelled how bilateral sensory information and a SNN model of the LAL behave in a snapshot navigation setup using Antworld. We compared the original snapshot navigation model using a panoramic Field of View with several combinations of the Core-Network and bilateral vision models: using a bilateral view, a bilateral view with the SNN, a panoramic view with SNN and other standard movement behaviours. We confirmed the findings of preliminary work, in an abstract setup, that had shown that a bilateral view combined with a SNN performs best to recover and approach navigation relevant locations. Also introducing models based on the steering framework into this visually complex environment improved the performance of agents performing snapshot navigation

Florida Undergraduate Research Conference

FURC serves as a multi-disciplinary conference through which undergraduate students from the state of Florida can present their research. February 16-17, 2024https://digitalcommons.unf.edu/university_events/1006/thumbnail.jp

Viewing Rate-Based Neurons as Biophysical Conductance Outputting Models

In the field of computational neuroscience, spiking neural network models are generally preferred over rate-based models due to their ability to model biological dynamics. Within AI, rate-based artificial neural networks have seen success in a wide variety of applications. In simplistic spiking models, information between neurons is transferred through discrete spikes, while rate-based neurons transfer information through continuous firing-rates. Here, we argue that while the spiking neuron model, when viewed in isolation, may be more biophysically accurate than rate-based models, the roles reverse when we also consider information transfer between neurons. In particular we consider the biological importance of continuous synaptic signals. We show how synaptic conductance relates to the common rate-based model, and how this relation elevates these models in terms of their biological soundness. We shall see how this is a logical relation by investigating mechanisms known to be present in biological synapses. We coin the term ‘conductance-outputting neurons’ to differentiate this alternative view from the standard firing-rate perspective. Finally, we discuss how this fresh view of rate-based models can open for further neuro-AI collaboration

Life Sciences Program Tasks and Bibliography

This document includes information on all peer reviewed projects funded by the Office of Life and Microgravity Sciences and Applications, Life Sciences Division during fiscal year 1995. Additionally, this inaugural edition of the Task Book includes information for FY 1994 programs. This document will be published annually and made available to scientists in the space life sciences field both as a hard copy and as an interactive Internet web pag

Enactive Cinema: Simulatorium Eisensteinense

The dissertation at hand explores the very grounds, within which the phenomenon of cinema emerges. It is a study of the intrinsic dynamics of cinema author’s mind in the process of creating moving image. Alas, it is not a historical, cultural, or ideological study into the handicraft, the narrative genres, or technological developments of cinema. Instead, it discusses possible foundations of cinema in the human nature, as seems viable in the light of the contemporary biological and psychological constraints. The dissertation is set to define a kind of cinema, which reflects the recent scientific knowledge about neural underpinnings of human activity, and which draws its emotional power from one’s experimental resources of understanding and interacting with others within the everyday world. While attribute of ‘enactive’ carries the explicit sense of pragmatic doing and meaningful acting in the world, it is the embodied simulation of the world, which will provide the cognitive environment for creative enactment. Emotions, in addition to determining unconscious, involuntary understanding about the state of things, also determine all conscious, intentional, and imaginative aspects of cognition. Faithful to the spirit of Eisenstein the dissertation deliberately deviates from other mainstream cinema research: instead of the spectator, the focus here is on the author’s cognitive processes