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Over the last four decades, the amazing success of deep learning has been driven by the use of Stochastic Gradient Descent (SGD) as the main optimization technique. The default implementation for the computation of the gradient for SGD is backpropagation, which, with its variations, is used to this day in almost all computer implementations. From the perspective of neuroscientists, however, the consensus is that backpropagation is unlikely to be used by the brain. Though several alternatives have been discussed, none is so far supported by experimental evidence. Here we propose a circuit for updating the weights in a network that is biologically plausible, works as well as backpropagation, and leads to verifiable predictions about the anatomy and the physiology of a characteristic motif of four plastic synapses between ascending and descending cortical streams. A key prediction of our proposal is a surprising property of self-assembly of the basic circuit, emerging from initial random connectivity and heterosynaptic plasticity rules. 

Artificial neural networks are being proposed as models of parts of the brain. The networks are compared to recordings of biological neurons, and good performance in reproducing neural responses is considered to support the model’s validity. A key question is how much this system identification approach tells us about brain computation. Does it validate one model architecture over another? We evaluate the most commonly used comparison techniques, such as a linear encoding model and centered kernel alignment, to correctly identify a model by replacing brain recordings with known ground truth models. System identification performance is quite variable; it also depends significantly on factors independent of the ground truth architecture, such as stimuli images. In addition, we show the limitations of using functional similarity scores in identifying higher-level architectural motifs. 

How much can you say about the gradient of a neural network without computing a loss or knowing the label? This may sound like a strange question: surely the answer is “very little.” However, in this paper, we show that gradients are more structured than previously thought. Gradients lie in a predictable low-dimensional subspace which depends on the network architecture and incoming features. Exploiting this structure can significantly improve gradient-free optimization schemes based on directional derivatives, which have struggled to scale beyond small networks trained on toy datasets. We study how to narrow the gap in optimization performance between methods that calculate exact gradients and those that use directional derivatives. Furthermore, we highlight new challenges in overcoming the large gap between optimizing with exact gradients and guessing the gradients. 

Abstract Cell migration is critical for tissue development and regeneration but requires extracellular environments that are conducive to motion. Cells may actively generate migratory routes in vivo by degrading or remodeling their environments or instead utilize existing extracellular matrix microstructures or microtracks as innate pathways for migration. While hydrogels in general are valuable tools for probing the extracellular regulators of 3-dimensional migration, few recapitulate these natural migration paths. Here, we develop a biopolymer-based bicontinuous hydrogel system that comprises a covalent hydrogel of enzymatically crosslinked gelatin and a physical hydrogel of guest and host moieties bonded to hyaluronic acid. Bicontinuous hydrogels form through controlled solution immiscibility, and their continuous subdomains and high micro-interfacial surface area enable rapid 3D migration, particularly when compared to homogeneous hydrogels. Migratory behavior is mesenchymal in nature and regulated by biochemical and biophysical signals from the hydrogel, which is shown across various cell types and physiologically relevant contexts (e.g., cell spheroids, ex vivo tissues, in vivo tissues). Our findings introduce a design that leverages important local interfaces to guide rapid cell migration. 

Various artificial neural networks developed by engineers have been evaluated as models of the brain, such as the ventral stream in the primate visual cortex. After being trained on large datasets, the network outputs are compared to recordings of biological neurons. Good performance in reproducing neural responses is taken as validation for the model. This system identification approach is different from the traditional ways to test theories and associated models in the natural sciences. Furthermore, it lacks a clear foundation in terms of theory and empirical validation. Here we begin characterizing some of these emerging approaches: what do they tell us? To address this question, we benchmark their ability to correctly identify a model by replacing the brain recordings with recordings from a known ground truth model. We evaluate commonly used identification techniques such as neural regression (linear regression on a population of model units) and centered kernel alignment (CKA). Even in the setting where the correct model is among the candidates, we find that the performance of these approaches at system identification is quite variable; it also depends significantly on factors independent of the ground truth architecture, such as scoring function and dataset.