Search

To adapt to their environments, animals learn associations between sensory stimuli and unconditioned stimuli. In invertebrates, olfactory associative learning primarily occurs in the mushroom body, which is segregated into separate compartments. Within each compartment, Kenyon cells (KCs) encoding sparse odor representations project onto mushroom body output neurons (MBONs) whose outputs guide behavior. Associated with each compartment is a dopamine neuron (DAN) that modulates plasticity of the KC-MBON synapses within the compartment. Interestingly, DAN-induced plasticity of the KC-MBON synapse is imbalanced in the sense that it only weakens the synapse and is temporally sparse. We propose a normative mechanistic model of the MBON as a linear discriminant analysis (LDA) classifier that predicts the presence of an unconditioned stimulus (class identity) given a KC odor representation (feature vector). Starting from a principled LDA objective function and under the assumption of temporally sparse DAN activity, we derive an online algorithm which maps onto the mushroom body compartment. Our model accounts for the imbalanced learning at the KC-MBON synapse and makes testable predictions that provide clear contrasts with existing models.

One major question in neuroscience is how to relate connectomes to neural activity, circuit function, and learning. We offer an answer in the peripheral olfactory circuit of the Drosophila larva, composed of olfactory receptor neurons (ORNs) connected through feedback loops with interconnected inhibitory local neurons (LNs). We combine structural and activity data and, using a holistic normative framework based on similarity-matching, we propose a biologically plausible mechanistic model of the circuit. Our model predicts the ORN → LN synaptic weights found in the connectome and demonstrate that they reflect correlations in ORN activity patterns. Additionally, our model explains the relation between ORN → LN and LN – LN synaptic weight and the arising of different LN types. This global synaptic organization can autonomously arise through Hebbian plasticity, and thus allows the circuit to adapt to different environments in an unsupervised manner. Functionally, we propose LNs extract redundant input correlations and dampen them in ORNs, thus partially whitening and normalizing the stimulus representations in ORNs. Our work proposes a comprehensive framework to combine structure, activity, function, and learning, and uncovers a general and potent circuit motif that can learn and extract significant input features and render stimulus representations more efficient.SignificanceThe brain represents information with patterns of neural activity. At the periphery, due to the properties of the external world and of encoding neurons, these patterns contain correlations, which are detrimental for stimulus discrimination. We study the peripheral olfactory neural circuit of the Drosophila larva, that preprocesses neural representations before relaying them to higher brain areas. A comprehensive understanding of this preprocessing is, however, lacking. Here, we propose a mechanistic and normative framework describing the function of the circuit and predict the circuit’s synaptic organization based on the circuit’s input neural activity. We show how the circuit can autonomously adapt to different environments, extracts stimulus features, and decorrelate and normalize input representations, which facilitates odor discrimination downstream.

Long-term memories and learned behavior are conventionally associated with stable neuronal representations. However, recent experiments showed that neural population codes in many brain areas continuously change even when animals have fully learned and stably perform their tasks. This representational “drift” naturally leads to questions about its causes, dynamics, and functions. Here, we explore the hypothesis that neural representations optimize a representational objective with a degenerate solution space, and noisy synaptic updates drive the network to explore this (near-)optimal space causing representational drift. We illustrate this idea in simple, biologically plausible Hebbian/anti-Hebbian network models of representation learning, which optimize similarity matching objectives, and, when neural outputs are constrained to be nonnegative, learn localized receptive fields (RFs) that tile the stimulus manifold. We find that the drifting RFs of individual neurons can be characterized by a coordinated random walk, with the effective diffusion constants depending on various parameters such as learning rate, noise amplitude, and input statistics. Despite such drift, the representational similarity of population codes is stable over time. Our model recapitulates recent experimental observations in hippocampus and posterior parietal cortex, and makes testable predictions that can be probed in future experiments.

As the study of the human brain is complicated by its sheer scale, complexity, and impracticality of invasive experiments, neuroscience research has long relied on model organisms. The brains of macaque, mouse, zebrafish, fruit fly, nematode, and others have yielded many secrets that advanced our understanding of the human brain. Here, we propose that adding miniature insects to this collection would reduce the costs and accelerate brain research. The smallest insects occupy a special place among miniature animals: despite their body sizes, comparable to unicellular organisms, they retain complex brains that include thousands of neurons. Their brains possess the advantages of those in insects, such as neuronal identifiability and the connectome stereotypy, yet are smaller and hence easier to map and understand. Finally, the brains of miniature insects offer insights into the evolution of brain design.

Advances in fluorescence microscopy enable monitoring larger brain areas in-vivo with finer time resolution. The resulting data rates require reproducible analysis pipelines that are reliable, fully automated, and scalable to datasets generated over the course of months. We present CaImAn, an open-source library for calcium imaging data analysis. CaImAn provides automatic and scalable methods to address problems common to pre-processing, including motion correction, neural activity identification, and registration across different sessions of data collection. It does this while requiring minimal user intervention, with good scalability on computers ranging from laptops to high-performance computing clusters. CaImAn is suitable for two-photon and one-photon imaging, and also enables real-time analysis on streaming data. To benchmark the performance of CaImAn we collected and combined a corpus of manual annotations from multiple labelers on nine mouse two-photon datasets. We demonstrate that CaImAn achieves near-human performance in detecting locations of active neurons., eLife digest 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.

Big data problems frequently require processing datasets in a streaming fashion, either because all data are available at once but collectively are larger than available memory or because the data intrinsically arrive one data point at a time and must be processed online. Here, we introduce a computationally efficient version of similarity matching, a framework for online dimensionality reduction that incrementally estimates the top K-dimensional principal subspace of streamed data while keeping in memory only the last sample and the current iterate. To assess the performance of our approach, we construct and make public a test suite containing both a synthetic data generator and the infrastructure to test online dimensionality reduction algorithms on real datasets, as well as performant implementations of our algorithm and competing algorithms with similar aims. Among the algorithms considered we find our approach to be competitive, performing among the best on both synthetic and real data., 9 pages, 4 figures