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Identifying cell types and understanding their functional properties is crucial for unraveling the mechanisms underlying perception and cognition. In the retina, functional types can be identified by carefully selected stimuli, but this requires expert domain knowledge and biases the procedure towards previously known cell types. In the visual cortex, it is still unknown what functional types exist and how to identify them. Thus, for unbiased identification of the functional cell types in retina and visual cortex, new approaches are needed. Here we propose an optimization-based clustering approach using deep predictive models to obtain functional clusters of neurons using Most Discriminative Stimuli (MDS). Our approach alternates between stimulus optimization with cluster reassignment akin to an expectation-maximization algorithm. The algorithm recovers functional clusters in mouse retina, marmoset retina and macaque visual area V4. This demonstrates that our approach can successfully find discriminative stimuli across species, stages of the visual system and recording techniques. The resulting most discriminative stimuli can be used to assign functional cell types fast and on the fly, without the need to train complex predictive models or show a large natural scene dataset, paving the way for experiments that were previously limited by experimental time. Crucially, MDS are interpretable: they visualize the distinctive stimulus patterns that most unambiguously identify a specific type of neuron.

Neural population responses in sensory systems are driven by external physical stimuli. This stimulus-response relationship is typically characterized by receptive fields, which have been estimated by neural system identification approaches. Such models usually requires a large amount of training data, yet, the recording time for animal experiments is limited, giving rise to epistemic uncertainty for the learned neural transfer functions. While deep neural network models have demonstrated excellent power on neural prediction, they usually do not provide the uncertainty of the resulting neural representations and derived statistics, such as the stimuli driving neurons optimally, from in silico experiments. Here, we present a Bayesian system identification approach to predict neural responses to visual stimuli, and explore whether explicitly modeling network weight variability can be beneficial for identifying neural response properties. To this end, we use variational inference to estimate the posterior distribution of each model weight given the training data. Tests with different neural datasets demonstrate that this method can achieve higher or comparable performance on neural prediction, with a much higher data efficiency compared to Monte Carlo dropout methods and traditional models using point estimates of the model parameters. Furthermore, our approach enables to identify response properties with credible intervals and perform statistical test for the learned neural features, which avoid the idiosyncrasy of a single model. Finally, in silico experiments show that our model generates stimuli driving neuronal activity significantly better than traditional models, particularly in the limited-data regime.

Spatio-temporal receptive field (STRF) models are frequently used to approximate the computation implemented by a sensory neuron. Typically, such STRFs are assumed to be smooth and sparse. Current state-of-the-art approaches for estimating STRFs based on empirical Bayes are often not computationally efficient in high-dimensional settings, as encountered in sensory neuroscience. Here we pursued an alternative approach and encode prior knowledge for estimation of STRFs by choosing a set of basis functions with the desired properties: natural cubic splines. Our method is computationally efficient and can be easily applied to a wide range of existing models. We compared the performance of spline-based methods to non-spline ones on simulated and experimental data, showing that spline-based methods consistently outperform the non-spline versions.

Neuroscientists classify neurons into different types that perform similar computations at different locations in the visual field. Traditional methods for neural system identification do not capitalize on this separation of 'what' and 'where'. Learning deep convolutional feature spaces that are shared among many neurons provides an exciting path forward, but the architectural design needs to account for data limitations: While new experimental techniques enable recordings from thousands of neurons, experimental time is limited so that one can sample only a small fraction of each neuron's response space. Here, we show that a major bottleneck for fitting convolutional neural networks (CNNs) to neural data is the estimation of the individual receptive field locations, a problem that has been scratched only at the surface thus far. We propose a CNN architecture with a sparse readout layer factorizing the spatial (where) and feature (what) dimensions. Our network scales well to thousands of neurons and short recordings and can be trained end-to-end. We evaluate this architecture on ground-truth data to explore the challenges and limitations of CNN-based system identification. Moreover, we show that our network model outperforms current state-of-the art system identification models of mouse primary visual cortex., Comment: NIPS 2017

A fundamental challenge in calcium imaging has been to infer the timing of action potentials from the measured noisy calcium fluorescence traces. We systematically evaluate a range of spike inference algorithms on a large benchmark dataset recorded from varying neural tissue (V1 and retina) using different calcium indicators (OGB-1 and GCamp6). We show that a new algorithm based on supervised learning in flexible probabilistic models outperforms all previously published techniques, setting a new standard for spike inference from calcium signals. Importantly, it performs better than other algorithms even on datasets not seen during training. Future data acquired in new experimental conditions can easily be used to further improve its spike prediction accuracy and generalization performance. Finally, we show that comparing algorithms on artificial data is not informative about performance on real population imaging data, suggesting that a benchmark dataset may greatly facilitate future algorithmic developments.