The Automation of Electrophysiological Experiments and Data Analysis

The role of computation in science is continually growing and neuroscience is no exception. Despite this, a severe lack of scientific software infrastructure persists, slowing progress in many domains. In this thesis, we will see how the combination of neuroscience and software engineering can build infrastructure that enables discovery. The first chapter discusses the Turtle Electrophysiology Project, or TEP, an experiment-automation and data-management system. This system has allowed us to automate away some of the most tedious tasks involved in conducting experiments. As a result, we can collect more data in less time, and with fewer errors related to the loss of metadata: information about how the data were collected). Also, since all of the metadata is automatically digitized during the experiment we can now completely automate our analyses. Chapters two and three are examples of research conducted using the ever-evolving TEP system. In the first instance, we used TEP to deliver visual stimuli and handle data-management. In chapter three, the experiments involved delivering electrical stimuli instead of visual stimuli, and much more rigorous analysis. And even though TEP was not specifically designed to handle collecting data this way, the flexible tags system enabled us to do so. Finally, chapter four details the construction of a robust analysis tool called Spikepy. Whereas TEP is specially designed for the turtle preparation we have, Spikepy is a general-purpose spike-sorting application and framework. Spikepy takes flexibility to the extreme by being a plugin-based framework, yet maintaining a very easy to use interface

Analytical methods and experimental approaches for electrophysiological studies of brain oscillations

Brain oscillations are increasingly the subject of electrophysiological studies probing their role in the functioning and dysfunction of the human brain. In recent years this research area has seen rapid and significant changes in the experimental approaches and analysis methods. This article reviews these developments and provides a structured overview of experimental approaches, spectral analysis techniques and methods to establish relationships between brain oscillations and behaviour

Comparative study of extracellular recording methods for analysis of afferent sensory information: Empirical modeling, data analysis and interpretation

Background: Physiological studies of sensorial systems often require the acquisition and processing of data extracted from their multiple components to evaluate how the neural information changes in relation to the environment changes. In this work, a comparative study about methodological aspects of two electrophysiological approaches is described. New method: Extracellular recordings from deep vibrissal nerves were obtained by using a customized microelectrode Utah array during passive mechanical stimulation of rat´s whiskers. These recordings were compared with those obtained with bipolar electrodes. We also propose here a simplified empirical model of the electrophysiological activity obtained from a bundle of myelinated nerve fibers. Results: The peripheral activity of the vibrissal system was characterized through the temporal and spectral features obtained with both recording methods. The empirical model not only allows the correlation between anatomical structures and functional features, but also allows to predict changes in the CAPs morphology when the arrangement and the geometry of the electrodes changes. Comparison with existing method(s): This study compares two extracellular recording methods based on analysis techniques, empirical modeling and data processing of vibrissal sensory information. Conclusions: This comparative study reveals a close relationship between the electrophysiological techniques and the processing methods necessary to extract sensory information. This relationship is the result of maximizing the extraction of information from recordings of sensory activity.Fil: Farfan, Fernando Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Departamento de Bioingeniería. Laboratorio de Medios e Interfases; ArgentinaFil: Soto Sanchez, Cristina. Universidad de Miguel Hernández; España. Consorcio Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina; EspañaFil: Pizá, Alvaro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Departamento de Bioingeniería. Laboratorio de Medios e Interfases; ArgentinaFil: Albarracin, Ana Lia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Departamento de Bioingeniería. Laboratorio de Medios e Interfases; ArgentinaFil: Soletta, Jorge Humberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Departamento de Bioingeniería. Laboratorio de Medios e Interfases; ArgentinaFil: Lucianna, Facundo Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Departamento de Bioingeniería. Laboratorio de Medios e Interfases; ArgentinaFil: Fernandez, Esteve. Universidad de Miguel Hernández; España. Consorcio Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina; Españ

Investigating information processing within the brain using multi-electrode array (MEA) electrophysiology data

How a stimulus, such as an odour, is represented in the brain is one of the main questions in neuroscience. It is becoming clearer that information is encoded by a population of neurons, but, how the spiking activity of a population of neurons conveys this information is unknown. Several population coding hypotheses have formulated over the years, and therefore, to obtain a more definitive answer as to how a population of neurons represents stimulus information we need to test, i.e. support or falsify, each of the hypotheses. One way of addressing these hypotheses is to record and analyse the activity of multiple individual neurons from the brain of a test subject when a stimulus is, and is not, presented. With the advent of multi electrode arrays (MEA) we can now record such activity. However, before we can investigate/test the population coding hypotheses using such recordings, we need to determine the number of neurons recorded by the MEA and their spiking activity, after spike detection, using an automatic spike sorting algorithm (we refer to the spiking activity of the neurons extracted from the MEA recordings as MEA sorted data). While there are many automatic spike sorting methods available, they have limitations. In addition, we are lacking methods to test/investigate the population coding hypotheses in detail using the MEA sorted data. That is, methods that show whether neurons respond in a hypothesised way and, if they do, shows how the stimulus is represented within the recorded area. Thus, in this thesis, we were motivated to, firstly, develop a new automatic spike sorting method, which avoids the limitations of other methods. We validated our method using simulated and biological data. In addition, we found our method can perform better than other standard methods. We next focused on the population rate coding hypothesis (i.e. the hypothesis that information is conveyed in the number of spikes fired by a pop- ulation of neurons within a relevant time period). More specifically, we developed a method for testing/investigating the population rate coding hypothesis using the MEA sorted data. That is, a method that uses the multi variate analysis of variance (MANOVA) test, where we modified its output, to show the most responsive subar- eas within the recorded area. We validated this using simulated and biological data. Finally, we investigated whether noise correlation between neurons (i.e. correlations in the trial to trial variability of the response of neurons to the same stimulus) in a rat's olfactory bulb can affect the amount of information a population rate code conveys about a set of stimuli. We found that noise correlation between neurons was predominately positive, which, ultimately, reduced the amount of information a population containing >45 neurons could convey about the stimuli by ~30%

ラット大脳新皮質における局所神経細胞群動特性の解明

Tohoku University川島隆太課

Neural Processing in the Three Layer Turtle Visual Cortex

In this thesis we investigate neural processing in turtle visual cortex. To this end, we characterize the nature of both spontaneous, ongoing neural activity as well as activity evoked by visual stimulation. Data are collected from whole brain eye-attached preparations, recording with extracellular and intracellular electrodes. We investigate the activity of action potentials as well as the slower local field potential activity. To investigate response properties, we explore spatial properties of receptive fields, temporal properties of spontaneous and evoked activity, response adaptation, and correlations between different types of activity as well as between activity recorded in different regions. To study the roles of rhythmic oscillations in the local field potential, we examine temporal and spectral properties of oscillations. We look at the distributions of durations of oscillatory bursts as well as the distributions of the dominant frequencies within those oscillations. We also investigate the variability of these features and produce similar results in a model simulation. Lastly, we investigate criticality and the statistics of neural activity over a range of scales in the turtle visual cortex. We use neuronal avalanches to reveal scale-free cortical dynamics and power-law statistics, which have been hypothesized to optimize information processing

The right hippocampus leads the bilateral integration of gamma-parsed lateralized information

It is unclear whether the two hippocampal lobes convey similar or different activities and how they cooperate. Spatial discrimination of electric fields in anesthetized rats allowed us to compare the pathway-specific field potentials corresponding to the gamma-paced CA3 output (CA1 Schaffer potentials) and CA3 somatic inhibition within and between sides. Bilateral excitatory Schaffer gamma waves are generally larger and lead from the right hemisphere with only moderate covariation of amplitude, and drive CA1 pyramidal units more strongly than unilateral waves. CA3 waves lock to the ipsilateral Schaffer potentials, although bilateral coherence was weak. Notably, Schaffer activity may run laterally, as seen after the disruption of the connecting pathways. Thus, asymmetric operations promote the entrainment of CA3-autonomous gamma oscillators bilaterally, synchronizing lateralized gamma strings to converge optimally on CA1 targets. The findings support the view that interhippocampal connections integrate different aspects of information that flow through the left and right lobes

Processing and analysis of multichannel extracellular neuronal signals: state-of-the-art and challenges

In recent years multichannel neuronal signal acquisition systems have allowed scientists to focus on research questions which were otherwise impossible. They act as a powerful means to study brain (dys)functions in in-vivo and in in-vitro animal models. Typically, each session of electrophysiological experiments with multichannel data acquisition systems generate large amount of raw data. For example, a 128 channel signal acquisition system with 16 bits A/D conversion and 20 kHz sampling rate will generate approximately 17 GB data per hour (uncompressed). This poses an important and challenging problem of inferring conclusions from the large amounts of acquired data. Thus, automated signal processing and analysis tools are becoming a key component in neuroscience research, facilitating extraction of relevant information from neuronal recordings in a reasonable time. The purpose of this review is to introduce the reader to the current state-of-the-art of open-source packages for (semi)automated processing and analysis of multichannel extracellular neuronal signals (i.e., neuronal spikes, local field potentials, electroencephalogram, etc.), and the existing Neuroinformatics infrastructure for tool and data sharing. The review is concluded by pinpointing some major challenges that are being faced, which include the development of novel benchmarking techniques, cloud-based distributed processing and analysis tools, as well as defining novel means to share and standardize data