skip to main content

Explore Research Products in the NSF-PAR

Title: NetPyNE, a tool for data-driven multiscale modeling of brain circuits
The approximately 100 billion neurons in our brain are responsible for everything we do and experience. Experiments aimed at discovering how these cells encode and process information generate vast amounts of data. These data span multiple scales, from interactions between individual molecules to coordinated waves of electrical activity that spread across the entire brain surface. To understand how the brain works, we must combine and make sense of these diverse types of information. Computational modeling provides one way of doing this. Using equations, we can calculate the chemical and electrical changes that take place in neurons. We can then build models of neurons and neural circuits that reproduce the patterns of activity seen in experiments. Exploring these models can provide insights into how the brain itself works. Several software tools are available to simulate neural circuits, but none provide an easy way of incorporating data that span different scales, from molecules to cells to networks. Moreover, most of the models require familiarity with computer programming. Dura-Bernal et al. have now developed a new software tool called NetPyNE, which allows users without programming expertise to build sophisticated models of brain circuits. It features a user-friendly interface for defining the properties of the model at molecular, cellular and circuit scales. It also provides an easy and automated method to identify the properties of the model that enable it to reproduce experimental data. Finally, NetPyNE makes it possible to run the model on supercomputers and offers a variety of ways to visualize and analyze the resulting output. Users can save the model and output in standardized formats, making them accessible to as many people as possible. Researchers in labs across the world have used NetPyNE to study different brain regions, phenomena and diseases. The software also features in courses that introduce students to neurobiology and computational modeling. NetPyNE can help to interpret isolated experimental findings, and also makes it easier to explore interactions between brain activity at different scales. This will enable researchers to decipher how the brain encodes and processes information, and ultimately could make it easier to understand and treat brain disorders.  more » « less
Award ID(s):
1904444
NSF-PAR ID:
10300070
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ; ; ;
Date Published:
Journal Name:
eLife
Volume:
8
ISSN:
2050-084X
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ( , eLife)
    Memories are an important part of how we think, understand the world around us, and plan out future actions. In the brain, memories are thought to be stored in a region called the hippocampus. When memories are formed, neurons store events that occur around the same time together. This might explain why often, in the brains of animals, the activity associated with retrieving memories is not just a snapshot of what happened at a specific moment-- it can also include information about what the animal might experience next. This can have a clear utility if animals use memories to predict what they might experience next and plan out future actions. Mathematically, this notion of predictiveness can be summarized by an algorithm known as the successor representation. This algorithm describes what the activity of neurons in the hippocampus looks like when retrieving memories and making predictions based on them. However, even though the successor representation can computationally reproduce the activity seen in the hippocampus when it is making predictions, it is unclear what biological mechanisms underpin this computation in the brain. Fang et al. approached this problem by trying to build a model that could generate the same activity patterns computed by the successor representation using only biological mechanisms known to exist in the hippocampus. First, they used computational methods to design a network of neurons that had the biological properties of neural networks in the hippocampus. They then used the network to simulate neural activity. The results show that the activity of the network they designed was able to exactly match the successor representation. Additionally, the data resulting from the simulated activity in the network fitted experimental observations of hippocampal activity in Tufted Titmice. One advantage of the network designed by Fang et al. is that it can generate predictions in flexible ways,. That is, it canmake both short and long-term predictions from what an individual is experiencing at the moment. This flexibility means that the network can be used to simulate how the hippocampus learns in a variety of cognitive tasks. Additionally, the network is robust to different conditions. Given that the brain has to be able to store memories in many different situations, this is a promising indication that this network may be a reasonable model of how the brain learns. The results of Fang et al. lay the groundwork for connecting biological mechanisms in the hippocampus at the cellular level to cognitive effects, an essential step to understanding the hippocampus, as well as its role in health and disease. For instance, their network may provide a concrete approach to studying how disruptions to the ways neurons make and break connections can impair memory formation. More generally, better models of the biological mechanisms involved in making computations in the hippocampus can help scientists better understand and test out theories about how memories are formed and stored in the brain. 
    more » « less
  2. ; ; ; ; ; ; ; ; ; ; et al ( , eLife)
    The human brain contains billions of cells called neurons that rapidly carry information from one part of the brain to another. Progress in medical research and healthcare is hindered by the difficulty in understanding precisely which neurons are active at any given time. New brain imaging techniques and genetic tools allow researchers to track the activity of thousands of neurons in living animals over many months. However, these experiments produce large volumes of data that researchers currently have to analyze manually, which can take a long time and generate irreproducible results. There is a need to develop new computational tools to analyze such data. The new tools should be able to operate on standard computers rather than just specialist equipment as this would limit the use of the solutions to particularly well-funded research teams. Ideally, the tools should also be able to operate in real-time as several experimental and therapeutic scenarios, like the control of robotic limbs, require this. To address this need, Giovannucci et al. developed a new software package called CaImAn to analyze brain images on a large scale. Firstly, the team developed algorithms that are suitable to analyze large sets of data on laptops and other standard computing equipment. These algorithms were then adapted to operate online in real-time. To test how well the new software performs against manual analysis by human researchers, Giovannucci et al. asked several trained human annotators to identify active neurons that were round or donut-shaped in several sets of imaging data from mouse brains. Each set of data was independently analyzed by three or four researchers who then discussed any neurons they disagreed on to generate a ‘consensus annotation’. Giovannucci et al. then used CaImAn to analyze the same sets of data and compared the results to the consensus annotations. This demonstrated that CaImAn is nearly as good as human researchers at identifying active neurons in brain images. CaImAn provides a quicker method to analyze large sets of brain imaging data and is currently used by over a hundred laboratories across the world. The software is open source, meaning that it is freely-available and that users are encouraged to customize it and collaborate with other users to develop it further. 
    more » « less
  3. ; ; ; ; ; ; ; ; ; ; et al ( , Science)
    INTRODUCTION A brainwide, synaptic-resolution connectivity map—a connectome—is essential for understanding how the brain generates behavior. However because of technological constraints imaging entire brains with electron microscopy (EM) and reconstructing circuits from such datasets has been challenging. To date, complete connectomes have been mapped for only three organisms, each with several hundred brain neurons: the nematode C. elegans , the larva of the sea squirt Ciona intestinalis , and of the marine annelid Platynereis dumerilii . Synapse-resolution circuit diagrams of larger brains, such as insects, fish, and mammals, have been approached by considering select subregions in isolation. However, neural computations span spatially dispersed but interconnected brain regions, and understanding any one computation requires the complete brain connectome with all its inputs and outputs. RATIONALE We therefore generated a connectome of an entire brain of a small insect, the larva of the fruit fly, Drosophila melanogaster. This animal displays a rich behavioral repertoire, including learning, value computation, and action selection, and shares homologous brain structures with adult Drosophila and larger insects. Powerful genetic tools are available for selective manipulation or recording of individual neuron types. In this tractable model system, hypotheses about the functional roles of specific neurons and circuit motifs revealed by the connectome can therefore be readily tested. RESULTS The complete synaptic-resolution connectome of the Drosophila larval brain comprises 3016 neurons and 548,000 synapses. We performed a detailed analysis of the brain circuit architecture, including connection and neuron types, network hubs, and circuit motifs. Most of the brain’s in-out hubs (73%) were postsynaptic to the learning center or presynaptic to the dopaminergic neurons that drive learning. We used graph spectral embedding to hierarchically cluster neurons based on synaptic connectivity into 93 neuron types, which were internally consistent based on other features, such as morphology and function. We developed an algorithm to track brainwide signal propagation across polysynaptic pathways and analyzed feedforward (from sensory to output) and feedback pathways, multisensory integration, and cross-hemisphere interactions. We found extensive multisensory integration throughout the brain and multiple interconnected pathways of varying depths from sensory neurons to output neurons forming a distributed processing network. The brain had a highly recurrent architecture, with 41% of neurons receiving long-range recurrent input. However, recurrence was not evenly distributed and was especially high in areas implicated in learning and action selection. Dopaminergic neurons that drive learning are amongst the most recurrent neurons in the brain. Many contralateral neurons, which projected across brain hemispheres, were in-out hubs and synapsed onto each other, facilitating extensive interhemispheric communication. We also analyzed interactions between the brain and nerve cord. We found that descending neurons targeted a small fraction of premotor elements that could play important roles in switching between locomotor states. A subset of descending neurons targeted low-order post-sensory interneurons likely modulating sensory processing. CONCLUSION The complete brain connectome of the Drosophila larva will be a lasting reference study, providing a basis for a multitude of theoretical and experimental studies of brain function. The approach and computational tools generated in this study will facilitate the analysis of future connectomes. Although the details of brain organization differ across the animal kingdom, many circuit architectures are conserved. As more brain connectomes of other organisms are mapped in the future, comparisons between them will reveal both common and therefore potentially optimal circuit architectures, as well as the idiosyncratic ones that underlie behavioral differences between organisms. Some of the architectural features observed in the Drosophila larval brain, including multilayer shortcuts and prominent nested recurrent loops, are found in state-of-the-art artificial neural networks, where they can compensate for a lack of network depth and support arbitrary, task-dependent computations. Such features could therefore increase the brain’s computational capacity, overcoming physiological constraints on the number of neurons. Future analysis of similarities and differences between brains and artificial neural networks may help in understanding brain computational principles and perhaps inspire new machine learning architectures. The connectome of the Drosophila larval brain. The morphologies of all brain neurons, reconstructed from a synapse-resolution EM volume, and the synaptic connectivity matrix of an entire brain. This connectivity information was used to hierarchically cluster all brains into 93 cell types, which were internally consistent based on morphology and known function. 
    more » « less
  4. ; ; ( , IEEE Transactions on Neural Networks and Learning Systems)
    null (Ed.)
    Variable binding is a cornerstone of symbolic reasoning and cognition. But how binding can be implemented in connectionist models has puzzled neuroscientists, cognitive psychologists, and neural network researchers for many decades. One type of connectionist model that naturally includes a binding operation is vector symbolic architectures (VSAs). In contrast to other proposals for variable binding, the binding operation in VSAs is dimensionality-preserving, which enables representing complex hierarchical data structures, such as trees, while avoiding a combinatoric expansion of dimensionality. Classical VSAs encode symbols by dense randomized vectors, in which information is distributed throughout the entire neuron population. By contrast, in the brain, features are encoded more locally, by the activity of single neurons or small groups of neurons, often forming sparse vectors of neural activation. Following Laiho et al. (2015), we explore symbolic reasoning with a special case of sparse distributed representations. Using techniques from compressed sensing, we first show that variable binding in classical VSAs is mathematically equivalent to tensor product binding between sparse feature vectors, another well-known binding operation which increases dimensionality. This theoretical result motivates us to study two dimensionality-preserving binding methods that include a reduction of the tensor matrix into a single sparse vector. One binding method for general sparse vectors uses random projections, the other, block-local circular convolution, is defined for sparse vectors with block structure, sparse block-codes. Our experiments reveal that block-local circular convolution binding has ideal properties, whereas random projection based binding also works, but is lossy. We demonstrate in example applications that a VSA with block-local circular convolution and sparse block-codes reaches similar performance as classical VSAs. Finally, we discuss our results in the context of neuroscience and neural networks. 
    more » « less
  5. ; ; ( , 2022 IEEE Symposium on Security and Privacy)
    Cryptographic tools like proof systems, multi-party computation, and fully homomorphic encryption are usually applied to computations expressed as systems of arithmetic constraints. In practice, this means that these applications rely on compilers from high-level programming languages (like C) to such constraints. This compilation task is challenging, but not entirely new: the software verification community has a rich literature on compiling programs to logical constraints (like SAT or SMT). In this work, we show that building shared compiler infrastructure for compiling to constraint representations is possible, because these representations share a common abstraction: stateless, non-uniform, non-deterministic computations that we call existentially quantified circuits, or EQCs. Moreover, we show that this shared infrastructure is useful, because it allows compilers for proof systems to benefit from decades of work on constraint compilation techniques for software verification. To make our approach concrete we create CirC, an infrastructure for building compilers to EQCs. CirC makes it easy to compile to new EQCs: we build support for three, R1CS (used for proof systems), SMT (used for verification and bug-finding), and ILP (used for optimization), in ≈2000 LOC. It’s also easy to extend CirC to support new source languages: we build a feature-complete compiler for a cryptographic language in one week and ≈900 LOC, whereas the reference compiler for the same language took years to write, comprises ≈24000 LOC, and produces worse-performing output than our compiler. Finally, CirC enables novel applications that combine multiple EQCs. For example, we build the first pipeline that (1) automatically identifies bugs in programs, then (2) automatically constructs cryptographic proofs of the bugs’ existence. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email