HippoUnit: A software tool for the automated testing and systematic comparison of detailed models of hippocampal neurons based on electrophysiological data

Anatomically and biophysically detailed data-driven neuronal models have become widely used tools for understanding and predicting the behavior and function of neurons. Due to the increasing availability of experimental data from anatomical and electrophysiological measurements as well as the growing number of computational and software tools that enable accurate neuronal modeling, there are now a large number of different models of many cell types available in the literature. These models were usually built to capture a few important or interesting properties of the given neuron type, and it is often unknown how they would behave outside their original context. In addition, there is currently no simple way of quantitatively comparing different models regarding how closely they match specific experimental observations. This limits the evaluation, re-use and further development of the existing models. Further, the development of new models could also be significantly facilitated by the ability to rapidly test the behavior of model candidates against the relevant collection of experimental data. We address these problems for the representative case of the CA1 pyramidal cell of the rat hippocampus by developing an open-source Python test suite, which makes it possible to automatically and systematically test multiple properties of models by making quantitative comparisons between the models and electrophysiological data. The tests cover various aspects of somatic behavior, and signal propagation and integration in apical dendrites. To demonstrate the utility of our approach, we applied our tests to compare the behavior of several different rat hippocampal CA1 pyramidal cell models from the ModelDB database against electrophysiological data available in the literature, and evaluated how well these models match experimental observations in different domains. We also show how we employed the test suite to aid the development of models within the European Human Brain Project (HBP), and describe the integration of the tests into the validation framework developed in the HBP, with the aim of facilitating more reproducible and transparent model building in the neuroscience community. Author summary Anatomically and biophysically detailed neuronal models are useful tools in neuroscience because they allow the prediction of the behavior and the function of the studied cell type under circumstances that are hard to investigate experimentally. However, most detailed biophysical models have been built to capture a few selected properties of the real neuron, and it is often unknown how they would behave under different circumstances, or whether they can be used to successfully answer different scientific questions. To help the modeling community develop better neural models, and to make the process of model building more reproducible and transparent, we developed a test suite that enables the comparison of the behavior of models of neurons in the rat hippocampus and their evaluation against experimental data. Applying our tests to several models available in the literature enabled us to assess and compare how precisely each of these models is able to match various electrophysiological properties of the real neurons. We also use the test suite in the model development workflow of the European Human Brain Project to aid the construction of better models of hippocampal neurons and networks.

Simple Neuron Models and Adaptation

Skander Mensi

Predicting activity of single neuron is an important part of the computational neuroscience and a great challenge. Several mathematical models exist, from the simple (one compartment and few parameters, like the SRM or the IF-type models), to the more complex (biophysical model like the Hodgkin-Huxley model). All these models have their own advantages and limitations, but no one is able to reproduce the exact behavior of real neurons. Multiple projects try to simulate complex neural networks, or even the whole brain (i.e. the blue brain project or other big network simulation). To achieve this goal it is very important that simple neuron models simulate, for a low computational cost, the precise activities of all neuron classes. It is well-known that neurons exhibit a lot of different activity patterns (from an electro-physiological point of view). Here we have focused on pyramidal neurons from the layer 5 of the neocortex. They are classified as regular spiking-cells. This cell type shows adaptation and like other neurons, refractoriness. Adaptation and refractoriness are very common neuronal activity in the brain, and so it is important to have a simple model which can reproduce this kind of activity. This project deals with two classical simple neuron models: the adaptive exponential integrate-and-fire model (AdEx) and the spike response model (SRM). We deter- mined the parameters of these two models using data generated with a detailed model, the Destexhe's model which is a HH-like model for cortical pyramidal cells, stimulated with different current injection scenarios. In a second time the model parameters have been set using data from in-vitro recordings of 4 layer 5 pyramidal rat neurons, stimulated with a sinusoid in vivo-like protocol, injected somatically in current-clamp configuration. Then we show that this type of model can capture adaptation and can reproduce the activity of neuron with a high reliability

2008

Interpretation of neuronal response properties with simplified neuron models

Laurent Badel

Computational neuroscience is a branch of the neurosciences that attempts to elucidate the principles underlying the operation of neurons with the help of mathematical modeling. In contrast with a number of fields pursuing a tightly related goal, such as machine learning or statistical learning, computational neuroscience emphasizes the realistic description of neuronal function and organization, and therefore requires a collaboration with experimental research in order to design new models and test their predictions. With the growing computational power available in modern computers, the simulation of neuronal networks with realistic numbers of neurons and functional organization is becoming routinely accessible. For the accurate design of such network models, the experimental characterization of neuronal response properties is required to probe the structural layout of biological networks at the single cell level. We develop here a novel method, the dynamic I-V method, that allows for the extraction of cellular response properties, and requires only a small amount of experimental data. Using this technique a simplified model of the neuronal response is obtained that is shown to accurately fit the experimental data. We demonstrate the use of the dynamic I-V method on both cortical pyramidal cells and inhibitory interneurons, and give the distributions of cellular parameters for the studied sample of cells. We also give theoretical results on the spike-triggered average, a quantity that is easily measured experimentally, which relate the neuronal response properties to identifiable features of the spike-triggered average, and can potentially be helpful to extend the dynamic I-V method in order to derive more accurate models. Potential applications and extensions of our results are discussed.

EPFL2009

A Pipeline Based Approach for Experimental Neuroscience Data Management

Muhammad Asif Jan

The field of neuroscience is witnessing a huge influx of experimental data thanks to the improvements in the data acquisition tools and techniques. Most of this data is being collected by thousands of experimenters located in various institutions around the world. There is also a growing interest in using this experimental data for building biologically realistic computational models of the neuronal systems. One such project i.e. the Blue Brain Project is developing a bottom-up neuronal modeling and simulation framework using experimental data collected at laboratories worldwide. However, to use the experimental data effectively in computational neuroscience research, the data needs to be annotated with metadata such as details of the experimental protocols and conditions, animal subject used etc. Most of the platforms for experimental neuroscience data management operate under the assumption that the primary data has been validated, and properly annotated before it is uploaded to the system. Thus putting the responsibility of validating, and annotating the experimental data with the experimenter conducting the study. Consequently, most experimenters maintain their own data using ad-hoc systems with non-standard metadata schemes; and only upload the final set of data to the data management platform. As a result, the metadata is usually incomplete, and does not always comply with the requirements of the data management platform, negatively impacting the reusability of their data. The current thesis work explored the question of the experimental data management within the context of the Blue Brain Project, and designs a data management pipeline catering for the acquisition, annotation and validation of the experimental data and associated metadata, in order to ensure that the data is usable for the computational modeling purposes. The pipeline enforces a data review process whereby incoming experimental data was made to go through a series of steps, analogous to the scientific review process, systematically improving the quality of the experimental data and associated metadata.