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BigNeuron is an open community bench-testing platform with the goal of setting open standards for accurate and fast automatic neuron tracing. We gathered a diverse set of image volumes across several species that is representative of the data obtained in many neuroscience laboratories interested in neuron tracing. Here, we report generated gold standard manual annotations for a subset of the available imaging datasets and quantified tracing quality for 35 automatic tracing algorithms. The goal of generating such a hand-curated diverse dataset is to advance the development of tracing algorithms and enable generalizable benchmarking. Together with image quality features, we pooled the data in an interactive web application that enables users and developers to perform principal component analysis, t-distributed stochastic neighbor embedding, correlation and clustering, visualization of imaging and tracing data, and benchmarking of automatic tracing algorithms in user-defined data subsets. The image quality metrics explain most of the variance in the data, followed by neuromorphological features related to neuron size. We observed that diverse algorithms can provide complementary information to obtain accurate results and developed a method to iteratively combine methods and generate consensus reconstructions. The consensus trees obtained provide estimates of the neuron structure ground truth that typically outperform single algorithms in noisy datasets. However, specific algorithms may outperform the consensus tree strategy in specific imaging conditions. Finally, to aid users in predicting the most accurate automatic tracing results without manual annotations for comparison, we used support vector machine regression to predict reconstruction quality given an image volume and a set of automatic tracings.

Neurons in the cerebral cortex receive thousands of synaptic inputs per second from thousands of presynaptic neurons. How the dendritic location of inputs, their timing, strength, and presynaptic origin, in conjunction with complex dendritic physiology, impact the transformation of synaptic input into action potential (AP) output remains generally unknown for in vivo conditions. Here, we introduce a computational approach to reveal which properties of the input causally underlie AP output, and how this neuronal input-output computation is influenced by the morphology and biophysical properties of the dendrites. We demonstrate that this approach allows dissecting of how different input populations drive in vivo observed APs. For this purpose, we focus on fast and broadly tuned responses that pyramidal tract neurons in layer 5 (L5PTs) of the rat barrel cortex elicit upon passive single whisker deflections. By reducing a multi-scale model that we reported previously, we show that three features are sufficient to predict with high accuracy the sensory responses and receptive fields of L5PTs under these specific in vivo conditions: the count of active excitatory versus inhibitory synapses preceding the response, their spatial distribution on the dendrites, and the AP history. Based on these three features, we derive an analytically tractable description of the input-output computation of L5PTs, which enabled us to dissect how synaptic input from thalamus and different cell types in barrel cortex contribute to these responses. We show that the input-output computation is preserved across L5PTs despite morphological and biophysical diversity of their dendrites. We found that trial-to-trial variability in L5PT responses, and cell-to-cell variability in their receptive fields, are sufficiently explained by variability in synaptic input from the network, whereas variability in biophysical and morphological properties have minor contributions. Our approach to derive analytically tractable models of input-output computations in L5PTs provides a roadmap to dissect network-neuron interactions underlying L5PT responses across different in vivo conditions and for other cell types. Author summary: Revealing how synaptic inputs drive action potential output is one of the major challenges in neuroscience research. An increasing number of approaches therefore seek to combine detailed measurements at synaptic, cellular and network scales into biologically realistic brain models. Indeed, such models have started to make empirically testable predictions about the inputs that underlie in vivo observed activity patterns. However, the enormous complexity of these models generally prevents the derivation of interpretable descriptions that explain how neurons transform synaptic input into action potential output, and how these input-output computations depend on synaptic, cellular and network properties. Here we introduce an approach to reveal input-output computations that neurons in the cerebral cortex perform upon sensory stimulation. For this purpose, we reduce a realistic multi-scale model of the rat barrel cortex to the minimal description that accounts for in vivo observed responses to whisker stimuli. Thereby, we identify the input-output computation that these cortical neurons perform under this in vivo condition, and we show that this computation is preserved across neurons despite morphological and biophysical diversity. Our approach provides analytically tractable and hence interpretable descriptions of neuronal input-output computations during specific in vivo conditions. [ABSTRACT FROM AUTHOR]

Abstract: Singing behavior in the adult male zebra finch is dependent upon the activity of a cortical region known as HVC (proper name). The vast majority of HVC projection neurons send primary axons to either the downstream premotor nucleus RA (robust nucleus of the arcopallium, or primary motor cortex) or Area X (basal ganglia), which play important roles in song production or song learning, respectively. In addition to these long‐range outputs, HVC neurons also send local axon collaterals throughout that nucleus. Despite their implications for a range of circuit models, these local processes have never been completely reconstructed. Here, we use in vivo single‐neuron Neurobiotin fills to examine 40 projection neurons across 31 birds with somatic positions distributed across HVC. We show that HVC(RA) and HVC(X) neurons have categorically distinct dendritic fields. Additionally, these cell classes send axon collaterals that are either restricted to a small portion of HVC (“local neurons”) or broadly distributed throughout the entire nucleus (“broadcast neurons”). Overall, these processes within HVC offer a structural basis for significant local processing underlying behaviorally relevant population activity. [ABSTRACT FROM AUTHOR]