Stephen M. Plaza

A visual motion detection circuit suggested by Drosophila connectomics

Animal behaviour arises from computations in neuronal circuits, but our understanding of these computations has been frustrated by the lack of detailed synaptic connection maps, or connectomes. For example, despite intensive investigations over half a century, the neuronal implementation of local motion detection in the insect visual system remains elusive. Here we develop a semi-automated pipeline using electron microscopy to reconstruct a connectome, containing 379 neurons and 8,637 chemical synaptic contacts, within the Drosophila optic medulla. By matching reconstructed neurons to examples from light microscopy, we assigned neurons to cell types and assembled a connectome of the repeating module of the medulla. Within this module, we identified cell types constituting a motion detection circuit, and showed that the connections onto individual motion-sensitive neurons in this circuit were consistent with their direction selectivity. Our results identify cellular targets for future functional investigations, and demonstrate that connectomes can provide key insights into neuronal computations.

BulletProof: a defect-tolerant CMP switch architecture

As silicon technologies move into the nanometer regime, transistor reliability is expected to wane as devices become subject to extreme process variation, particle-induced transient errors, and transistor wear-out. Unless these challenges are addressed, computer vendors can expect low yields and short mean-times-to-failure. In this paper, we examine the challenges of designing complex computing systems in the presence of transient and permanent faults. We select one small aspect of a typical chip multiprocessor (CMP) system to study in detail, a single CMP router switch. To start, we develop a unified model of faults, based on the time-tested bathtub curve. Using this convenient abstraction, we analyze the reliability versus area tradeoff across a wide spectrum of CMP switch designs, ranging from unprotected designs to fully protected designs with online repair and recovery capabilities. Protection is considered at multiple levels from the entire system down through arbitrary partitions of the design. To better understand the impact of these faults, we evaluate our CMP switch designs using circuit-level timing on detailed physical layouts. Our experimental results are quite illuminating. We find that designs are attainable that can tolerate a larger number of defects with less overhead than naive triple-modular redundancy, using domain-specific techniques such as end-to-end error detection, resource sparing, automatic circuit decomposition, and iterative diagnosis and reconfiguration.

Signature-Based SER Analysis and Design of Logic Circuits

We explore the use of signatures, i.e., partial truth tables generated via bit-parallel functional simulation, during soft error analysis and logic synthesis. We first present a signature-based CAD framework that incorporates tools for the logic-level analysis of soft error rate (x) and for signature-based design for reliability (SiDeR). We observe that the soft error rate (SER) of a logic circuit is closely related to various testability parameters, such as signal observability and probability. We show that these parameters can be computed very efficiently (in linear time) by means of signatures. Consequently, AnSER evaluates logic masking two to three orders of magnitude faster than other SER evaluators while maintaining accuracy. AnSER can also compute SER efficiently in sequential circuits by approximating steady-state probabilities and sequential signal observabilities. In the second part of this paper, we incorporate AnSER into logic synthesis design flows aimed at reliable circuit design. SiDeR identifies and exploits redundancy already present in a circuit via signature comparison to decrease SER. We show that SiDeR reduces SER by 40% with only 13% area overhead. We also describe a second signature-based synthesis strategy that employs local rewriting to simultaneously improve area and decrease SER. This technique yields 13% reduction in SER with a 2% area decrease. We show that combining the two synthesis approaches can result in further area-reliability improvements.

Synaptic circuits and their variations within different columns in the visual system of Drosophila

Significance Circuit diagrams of brains are generally reported only as absolute or consensus networks; these diagrams fail to identify the accuracy of connections, however, for which multiple circuits of the same neurons must be documented. For this reason, the modular composition of the Drosophila visual system, with many identified neuron classes, is ideal. Using EM, we identified synaptic connections in the fly’s second visual relay neuropil, or medulla, in the 20 neuron classes in a so-called “core connectome,” those neurons present in seven neighboring columns. These connections identify circuits for motion. Their error rates for wiring reveal that <1% of contacts overall are not part of a consensus circuit but incorporate errors of either omission or commission. Autapses are occasionally seen. We reconstructed the synaptic circuits of seven columns in the second neuropil or medulla behind the fly’s compound eye. These neurons embody some of the most stereotyped circuits in one of the most miniaturized of animal brains. The reconstructions allow us, for the first time to our knowledge, to study variations between circuits in the medulla’s neighboring columns. This variation in the number of synapses and the types of their synaptic partners has previously been little addressed because methods that visualize multiple circuits have not resolved detailed connections, and existing connectomic studies, which can see such connections, have not so far examined multiple reconstructions of the same circuit. Here, we address the omission by comparing the circuits common to all seven columns to assess variation in their connection strengths and the resultant rates of several different and distinct types of connection error. Error rates reveal that, overall, <1% of contacts are not part of a consensus circuit, and we classify those contacts that supplement (E+) or are missing from it (E−). Autapses, in which the same cell is both presynaptic and postsynaptic at the same synapse, are occasionally seen; two cells in particular, Dm9 and Mi1, form ≥20-fold more autapses than do other neurons. These results delimit the accuracy of developmental events that establish and normally maintain synaptic circuits with such precision, and thereby address the operation of such circuits. They also establish a precedent for error rates that will be required in the new science of connectomics.

Toward large-scale connectome reconstructions

Recent results have shown the possibility of both reconstructing connectomes of small but biologically interesting circuits and extracting from these connectomes insights into their function. However, these reconstructions were heroic proof-of-concept experiments, requiring person-months of effort per neuron reconstructed, and will not scale to larger circuits, much less the brains of entire animals. In this paper we examine what will be required to generate and use substantially larger connectomes, finding five areas that need increased attention: firstly, imaging better suited to automatic reconstruction, with excellent z-resolution; secondly, automatic detection, validation, and measurement of synapses; thirdly, reconstruction methods that keep and use uncertainty metrics for every object, from initial images, through segmentation, reconstruction, and connectome queries; fourthly, processes that are fully incremental, so that the connectome may be used before it is fully complete; and finally, better tools for analysis of connectomes, once they are obtained.

Solving the Third-Shift Problem in IC Piracy With Test-Aware Logic Locking

The increasing IC manufacturing cost encourages a business model where design houses outsource IC fabrication to remote foundries. Despite cost savings, this model exposes design houses to IC piracy as remote foundries can manufacture in excess to sell on the black market. Recent efforts in digital hardware security aim to thwart piracy by using XOR-based chip locking, cryptography, and active metering. To counter direct attacks and lower the exposure of unlocked circuits to the foundry, we introduce a multiplexor-based locking strategy that preserves test response allowing IC testing by an untrusted party before activation. We demonstrate a simple yet effective attack against a locked circuit that does not preserve test response, and validate the effectiveness of our locking strategy on IWLS 2005 benchmarks.

A connectome of a learning and memory center in the adult Drosophila brain

Understanding memory formation, storage and retrieval requires knowledge of the underlying neuronal circuits. In Drosophila, the mushroom body (MB) is the major site of associative learning. We reconstructed the morphologies and synaptic connections of all 983 neurons within the three functional units, or compartments, that compose the adult MB’s α lobe, using a dataset of isotropic 8 nm voxels collected by focused ion-beam milling scanning electron microscopy. We found that Kenyon cells (KCs), whose sparse activity encodes sensory information, each make multiple en passant synapses to MB output neurons (MBONs) in each compartment. Some MBONs have inputs from all KCs, while others differentially sample sensory modalities. Only 6% of KC>MBON synapses receive a direct synapse from a dopaminergic neuron (DAN). We identified two unanticipated classes of synapses, KC>DAN and DAN>MBON. DAN activation produces a slow depolarization of the MBON in these DAN>MBON synapses and can weaken memory recall. DOI: http://dx.doi.org/10.7554/eLife.26975.001

Graph-based active learning of agglomeration (GALA): a Python library to segment 2D and 3D neuroimages

The aim in high-resolution connectomics is to reconstruct complete neuronal connectivity in a tissue. Currently, the only technology capable of resolving the smallest neuronal processes is electron microscopy (EM). Thus, a common approach to network reconstruction is to perform (error-prone) automatic segmentation of EM images, followed by manual proofreading by experts to fix errors. We have developed an algorithm and software library to not only improve the accuracy of the initial automatic segmentation, but also point out the image coordinates where it is likely to have made errors. Our software, called gala (graph-based active learning of agglomeration), improves the state of the art in agglomerative image segmentation. It is implemented in Python and makes extensive use of the scientific Python stack (numpy, scipy, networkx, scikit-learn, scikit-image, and others). We present here the software architecture of the gala library, and discuss several designs that we consider would be generally useful for other segmentation packages. We also discuss the current limitations of the gala library and how we intend to address them.

Multicut brings automated neurite segmentation closer to human performance

Reference EPFL-ARTICLE-226946doi:10.1038/nmeth.4151View record in Web of Science Record created on 2017-03-27, modified on 2017-07-13

A context-aware delayed agglomeration framework for electron microscopy segmentation.

Electron Microscopy (EM) image (or volume) segmentation has become significantly important in recent years as an instrument for connectomics. This paper proposes a novel agglomerative framework for EM segmentation. In particular, given an over-segmented image or volume, we propose a novel framework for accurately clustering regions of the same neuron. Unlike existing agglomerative methods, the proposed context-aware algorithm divides superpixels (over-segmented regions) of different biological entities into different subsets and agglomerates them separately. In addition, this paper describes a “delayed” scheme for agglomerative clustering that postpones some of the merge decisions, pertaining to newly formed bodies, in order to generate a more confident boundary prediction. We report significant improvements attained by the proposed approach in segmentation accuracy over existing standard methods on 2D and 3D datasets.