Neuronal diversity and stereotypy at multiple scales through whole brain morphometry.

We conducted a large-scale whole-brain morphometry study by analyzing 3.7 peta-voxels of mouse brain images at the single-cell resolution, producing one of the largest multi-morphometry databases of mammalian brains to date. We registered 204 mouse brains of three major imaging modalities to the Allen Common Coordinate Framework (CCF) atlas, annotated 182,497 neuronal cell bodies, modeled 15,441 dendritic microenvironments, characterized the full morphology of 1876 neurons along with their axonal motifs, and detected 2.

Dendritome Mapping Unveils Spatial Organization of Striatal D1/D2-Neuron Morphology.

Morphology is a cardinal feature of a neuron that mediates its functions, but profiling neuronal morphologies at scale remains a formidable challenge. Here we describe a generalizable pipeline for large-scale brainwide study of dendritic morphology of genetically-defined single neurons in the mouse brain. We generated a dataset of 3,762 3D-reconstructed and reference-atlas mapped striatal D1- and D2- medium spiny neurons (MSNs).

A novel method for clustering cellular data to improve classification.

Many fields, such as neuroscience, are experiencing the vast proliferation of cellular data, underscoring the need for organizing and interpreting large datasets. A popular approach partitions data into manageable subsets via hierarchical clustering, but objective methods to determine the appropriate classification granularity are missing. We recently introduced a technique to systematically identify when to stop subdividing clusters based on the fundamental principle that cells must differ more between than within clusters.

Formation and retrieval of cell assemblies in a biologically realistic spiking neural network model of area CA3 in the mouse hippocampus.

The hippocampal formation is critical for episodic memory, with area Cornu Ammonis 3 (CA3) a necessary substrate for auto-associative pattern completion. Recent theoretical and experimental evidence suggests that the formation and retrieval of cell assemblies enable these functions. Yet, how cell assemblies are formed and retrieved in a full-scale spiking neural network (SNN) of CA3 that incorporates the observed diversity of neurons and connections within this circuit is not well understood.

Accelerating the continuous community sharing of digital neuromorphology data.

The tree-like morphology of neurons and glia is a key cellular determinant of circuit connectivity and metabolic function in the nervous system of essentially all animals. To elucidate the contribution of specific cell types to both physiological and pathological brain states, it is important to access detailed neuroanatomy data for quantitative analysis and computational modeling. NeuroMorpho.

A Continuous Attractor Model with Realistic Neural and Synaptic Properties Quantitatively Reproduces Grid Cell Physiology.

Computational simulations with data-driven physiological detail can foster a deeper understanding of the neural mechanisms involved in cognition. Here, we utilize the wealth of cellular properties from Hippocampome.org to study neural mechanisms of spatial coding with a spiking continuous attractor network model of medial entorhinal cortex circuit activity.

A Continuous Attractor Model with Realistic Neural and Synaptic Properties Quantitatively Reproduces Grid Cell Physiology.

Computational simulations with data-driven physiological detail can foster a deeper understanding of the neural mechanisms involved in cognition. Here, we utilize the wealth of cellular properties from Hippocampome.org to study neural mechanisms of spatial coding with a spiking continuous attractor network model of medial entorhinal cortex circuit activity.

Formation and Retrieval of Cell Assemblies in a Biologically Realistic Spiking Neural Network Model of Area CA3 in the Mouse Hippocampus.

The hippocampal formation is critical for episodic memory, with area Cornu Ammonis 3 (CA3) a necessary substrate for auto-associative pattern completion. Recent theoretical and experimental evidence suggests that the formation and retrieval of cell assemblies enable these functions. Yet, how cell assemblies are formed and retrieved in a full-scale spiking neural network (SNN) of CA3 that incorporates the observed diversity of neurons and connections within this circuit is not well understood.

Accelerating the continuous community sharing of digital neuromorphology data.

The tree-like morphology of neurons and glia is a key cellular determinant of circuit connectivity and metabolic function in the nervous system of essentially all animals. To elucidate the contribution of specific cell types to both physiological and pathological brain states, it is important to access detailed neuroanatomy data for quantitative analysis and computational modeling. NeuroMorpho.

A Novel Method for Clustering Cellular Data to Improve Classification.

Many fields, such as neuroscience, are experiencing the vast proliferation of cellular data, underscoring the need for organizing and interpreting large datasets. A popular approach partitions data into manageable subsets via hierarchical clustering, but objective methods to determine the appropriate classification granularity are missing. We recently introduced a technique to systematically identify when to stop subdividing clusters based on the fundamental principle that cells must differ more between than within clusters.

Unsupervised classification of brain-wide axons reveals the presubiculum neuronal projection blueprint.

We present a quantitative strategy to identify all projection neuron types from a given region with statistically different patterns of anatomical targeting. We first validate the technique with mouse primary motor cortex layer 6 data, yielding two clusters consistent with cortico-thalamic and intra-telencephalic neurons. We next analyze the presubiculum, a less-explored region, identifying five classes of projecting neurons with unique patterns of divergence, convergence, and specificity.

Hippocampome.org 2.0 is a knowledge base enabling data-driven spiking neural network simulations of rodent hippocampal circuits.

Hippocampome.org is a mature open-access knowledge base of the rodent hippocampal formation focusing on neuron types and their properties. Previously, Hippocampome.

Bibliometric analysis of neuroscience publications quantifies the impact of data sharing.

Summary: Neural morphology, the branching geometry of brain cells, is an essential cellular substrate of nervous system function and pathology. Despite the accelerating production of digital reconstructions of neural morphology, the public accessibility of data remains a core issue in neuroscience. Deficiencies in the availability of existing data create redundancy of research efforts and limit synergy.

Online conversion of reconstructed neural morphologies into standardized SWC format.

Digital reconstructions provide an accurate and reliable way to store, share, model, quantify, and analyze neural morphology. Continuous advances in cellular labeling, tissue processing, microscopic imaging, and automated tracing catalyzed a proliferation of software applications to reconstruct neural morphology. These computer programs typically encode the data in custom file formats.

Combinatorial quantification of distinct neural projections from retrograde tracing.

Comprehensive quantification of neuronal architectures underlying anatomical brain connectivity remains challenging. We introduce a method to identify distinct axonal projection patterns from a source to a set of target regions and the count of neurons with each pattern. A source region projecting to n targets could have 2-1 theoretically possible projection types, although only a subset of these types typically exists.

Whole human-brain mapping of single cortical neurons for profiling morphological diversity and stereotypy.

Quantifying neuron morphology and distribution at the whole-brain scale is essential to understand the structure and diversity of cell types. It is exceedingly challenging to reuse recent technologies of single-cell labeling and whole-brain imaging to study human brains. We propose adaptive cell tomography (ACTomography), a low-cost, high-throughput, and high-efficacy tomography approach, based on adaptive targeting of individual cells.

Bibliometric analysis of neuroscience publications quantifies the impact of data sharing.

Motivation: Neural morphology, the branching geometry of neurons and glia in the nervous system, is an essential cellular substrate of brain function and pathology. Despite the accelerating production of digital reconstructions of neural morphology in laboratories worldwide, the public accessibility of data remains a core issue in neuroscience. Deficiencies in the availability of existing data create redundancy of research efforts and prevent researchers from building on others' work.

Automatic identification of scientific publications describing digital reconstructions of neural morphology.

The increasing number of peer-reviewed publications constitutes a challenge for biocuration. For example, NeuroMorpho.Org, a sharing platform for digital reconstructions of neural morphology, must evaluate more than 6000 potentially relevant articles per year to identify data of interest.

Robust Resting-State Dynamics in a Large-Scale Spiking Neural Network Model of Area CA3 in the Mouse Hippocampus.

Hippocampal area CA3 performs the critical auto-associative function underlying pattern completion in episodic memory. Without external inputs, the electrical activity of this neural circuit reflects the spontaneous spiking interplay among glutamatergic pyramidal neurons and GABAergic interneurons. However, the network mechanisms underlying these resting-state firing patterns are poorly understood.

Full-Spectrum Neuronal Diversity and Stereotypy through Whole Brain Morphometry.

We conducted a large-scale study of whole-brain morphometry, analyzing 3.7 peta-voxels of mouse brain images at the single-cell resolution, producing one of the largest multi-morphometry databases of mammalian brains to date. We spatially registered 205 mouse brains and associated data from six Brain Initiative Cell Census Network (BICCN) data sources covering three major imaging modalities from five collaborative projects to the Allen Common Coordinate Framework (CCF) atlas, annotated 3D locations of cell bodies of 227,581 neurons, modeled 15,441 dendritic microenvironments, characterized the full morphology of 1,891 neurons along with their axonal motifs, and detected 2.

Unsupervised classification of brain-wide axons reveals neuronal projection blueprint.

Long-range axonal projections are quintessential determinants of network connectivity, linking cellular organization and circuit architecture. Here we introduce a quantitative strategy to identify, from a given source region, all "projection neuron types" with statistically different patterns of anatomical targeting. We first validate the proposed technique with well-characterized data from layer 6 of the mouse primary motor cortex.

Hippocampome.org v2.0: a knowledge base enabling data-driven spiking neural network simulations of rodent hippocampal circuits.

Hippocampome.org is a mature open-access knowledge base of the rodent hippocampal formation focusing on neuron types and their properties. Hippocampome.