Network Structure and Function in the Input Stage of the Cerebellar Cortex

It has long been recognised that neuronal networks are complex systems, whose dynamics depend on the properties of the individual synapses and neurons and the way in which they are interconnected. However, establishing clear links between network structure and function has proven difficult. To address this question I applied tools and techniques from computational neuroscience, neuroinformatics, information theory, machine learning, spatial point process theory and network theory, deploying them on a suitable HPC infrastructure where appropriate. Moreover, access to electrophysiological and anatomical data enabled me to develop biologically accurate models and to compare my theoretical predictions with analyses of raw data. In this work, I focused on the granule cell layer (GCL), the input stage of the cerebellar cortex. The GCL is particularly well suited to this type of analysis, as its structural characteristics are comparatively regular, well known and conserved across animal species, and several of its basic functions are relatively well understood. I showed that the synaptic connectivity in simple feed forward networks like the GCL governs the trade-off between information transmission and sparsification of incoming signals. This suggests a link between the functional requirements for the network and the strong evolutionary conservation of the anatomy of the cerebellar GCL. Furthermore, I investigated how the geometry of the GCL interacts with the spatial constraints of synaptic connectivity and gives rise to the statistical features of the chemically and electrically coupled networks formed by mossy fibres, granule cells and Golgi cells. Finally, I studied the influence of the spatial structure of the Golgi cell network on the robustness of the synchronous activity state it can support

Embo: a Python package for empirical data analysis using the Information Bottleneck

We present embo, a Python package to analyze empirical data using the Information Bottleneck (IB) method and its variants, such as the Deterministic Information Bottleneck (DIB). Given two random variables X and Y, the IB finds the stochastic mapping M of X that encodes the most information about Y, subject to a constraint on the information that M is allowed to retain about X. Despite the popularity of the IB, an accessible implementation of the reference algorithm oriented towards ease of use on empirical data was missing. Embo is optimized for the common case of discrete, lowdimensional data. Embo is fast, provides a standard data-processing pipeline, offers a parallel implementation of key computational steps, and includes reasonable defaults for the method parameters. Embo is broadly applicable to different problem domains, as it can be employed with any dataset consisting in joint observations of two discrete variables. It is available from the Python Package Index (PyPI), Zenodo and GitLab

Synthesizing realistic neural population activity patterns using generative adversarial networks

The ability to synthesize realistic patterns of neural activity is crucial for studying neural information processing. Here we used the Generative Adversarial Networks (GANs) framework to simulate the concerted activity of a population of neurons. We adapted the Wasserstein-GAN variant to facilitate the generation of unconstrained neural population activity patterns while still benefiting from parameter sharing in the temporal domain. We demonstrate that our proposed GAN, which we termed Spike-GAN, generates spike trains that match accurately the first- and second-order statistics of datasets of tens of neurons and also approximates well their higher-order statistics. We applied Spike-GAN to a real dataset recorded from salamander retina and showed that it performs as well as state-of-the-art approaches based on the maximum entropy and the dichotomized Gaussian frameworks. Importantly, Spike-GAN does not require to specify a priori the statistics to be matched by the model, and so constitutes a more flexible method than these alternative approaches. Finally, we show how to exploit a trained Spike-GAN to construct’importance maps’ to detect the most relevant statistical structures present in a spike train. Spike-GAN provides a powerful, easy-to-use technique for generating realistic spiking neural activity and for describing the most relevant features of the large-scale neural population recordings studied in modern systems neuroscience

Rat sensitivity to multipoint statistics is predicted by efficient coding of natural scenes

Efficient processing of sensory data requires adapting the neuronal encoding strategy to the statistics of natural stimuli. Previously, in Hermundstad et al., 2014, we showed that local multipoint correlation patterns that are most variable in natural images are also the most percep-tually salient for human observers, in a way that is compatible with the efficient coding principle. Understanding the neuronal mechanisms underlying such adaptation to image statistics will require performing invasive experiments that are impossible in humans. Therefore, it is important to under-stand whether a similar phenomenon can be detected in animal species that allow for powerful experimental manipulations, such as rodents. Here we selected four image statistics (from single-to four-point correlations) and trained four groups of rats to discriminate between white noise patterns and binary textures containing variable intensity levels of one of such statistics. We interpreted the resulting psychometric data with an ideal observer model, finding a sharp decrease in sensitivity from two-to four-point correlations and a further decrease from four-to three-point. This ranking fully reproduces the trend we previously observed in humans, thus extending a direct demonstration of efficient coding to a species where neuronal and developmental processes can be interrogated and causally manipulated

Temporal stability of stimulus representation increases along rodent visual cortical hierarchies

Cortical representations of brief, static stimuli become more invariant to identity-preserving transformations along the ventral stream. Likewise, increased invariance along the visual hierarchy should imply greater temporal persistence of temporally structured dynamic stimuli, possibly complemented by temporal broadening of neuronal receptive fields. However, such stimuli could engage adaptive and predictive processes, whose impact on neural coding dynamics is unknown. By probing the rat analog of the ventral stream with movies, we uncovered a hierarchy of temporal scales, with deeper areas encoding visual information more persistently. Furthermore, the impact of intrinsic dynamics on the stability of stimulus representations grew gradually along the hierarchy. A database of recordings from mouse showed similar trends, additionally revealing dependencies on the behavioral state. Overall, these findings show that visual representations become progressively more stable along rodent visual processing hierarchies, with an important contribution provided by intrinsic processing

Time as a supervisor: temporal regularity and auditory object learning

Sensory systems appear to learn to transform incoming sensory information into perceptual representations, or “objects,” that can inform and guide behavior with minimal explicit supervision. Here, we propose that the auditory system can achieve this goal by using time as a supervisor, i.e., by learning features of a stimulus that are temporally regular. We will show that this procedure generates a feature space sufficient to support fundamental computations of auditory perception. In detail, we consider the problem of discriminating between instances of a prototypical class of natural auditory objects, i.e., rhesus macaque vocalizations. We test discrimination in two ethologically relevant tasks: discrimination in a cluttered acoustic background and generalization to discriminate between novel exemplars. We show that an algorithm that learns these temporally regular features affords better or equivalent discrimination and generalization than conventional feature-selection algorithms, i.e., principal component analysis and independent component analysis. Our findings suggest that the slow temporal features of auditory stimuli may be sufficient for parsing auditory scenes and that the auditory brain could utilize these slowly changing temporal features

LEMS: a language for expressing complex biological models in concise and hierarchical form and its use in underpinning NeuroML 2.

Computational models are increasingly important for studying complex neurophysiological systems. As scientific tools, it is essential that such models can be reproduced and critically evaluated by a range of scientists. However, published models are currently implemented using a diverse set of modeling approaches, simulation tools, and computer languages making them inaccessible and difficult to reproduce. Models also typically contain concepts that are tightly linked to domain-specific simulators, or depend on knowledge that is described exclusively in text-based documentation. To address these issues we have developed a compact, hierarchical, XML-based language called LEMS (Low Entropy Model Specification), that can define the structure and dynamics of a wide range of biological models in a fully machine readable format. We describe how LEMS underpins the latest version of NeuroML and show that this framework can define models of ion channels, synapses, neurons and networks. Unit handling, often a source of error when reusing models, is built into the core of the language by specifying physical quantities in models in terms of the base dimensions. We show how LEMS, together with the open source Java and Python based libraries we have developed, facilitates the generation of scripts for multiple neuronal simulators and provides a route for simulator free code generation. We establish that LEMS can be used to define models from systems biology and map them to neuroscience-domain specific simulators, enabling models to be shared between these traditionally separate disciplines. LEMS and NeuroML 2 provide a new, comprehensive framework for defining computational models of neuronal and other biological systems in a machine readable format, making them more reproducible and increasing the transparency and accessibility of their underlying structure and properties

Dynamics of cortical contrast adaptation predict perception of signals in noise

Neurons throughout the sensory pathway adapt their responses depending on the statistical structure of the sensory environment. Contrast gain control is a form of adaptation in the auditory cortex, but it is unclear whether the dynamics of gain control reflect efficient adaptation, and whether they shape behavioral perception. Here, we trained mice to detect a target presented in background noise shortly after a change in the contrast of the background. The observed changes in cortical gain and behavioral detection followed the dynamics of a normative model of efficient contrast gain control; specifically, target detection and sensitivity improved slowly in low contrast, but degraded rapidly in high contrast. Auditory cortex was required for this task, and cortical responses were not only similarly affected by contrast but predicted variability in behavioral performance. Combined, our results demonstrate that dynamic gain adaptation supports efficient coding in auditory cortex and predicts the perception of sounds in noise

Open Source Brain: A Collaborative Resource for Visualizing, Analyzing, Simulating, and Developing Standardized Models of Neurons and Circuits

Computational models are powerful tools for exploring the properties of complex biological systems. In neuroscience, data-driven models of neural circuits that span multiple scales are increasingly being used to understand brain function in health and disease. But their adoption and reuse has been limited by the specialist knowledge required to evaluate and use them. To address this, we have developed Open Source Brain, a platform for sharing, viewing, analyzing, and simulating standardized models from different brain regions and species. Model structure and parameters can be automatically visualized and their dynamical properties explored through browser-based simulations. Infrastructure and tools for collaborative interaction, development, and testing are also provided. We demonstrate how existing components can be reused by constructing new models of inhibition-stabilized cortical networks that match recent experimental results. These features of Open Source Brain improve the accessibility, transparency, and reproducibility of models and facilitate their reuse by the wider community