Potential Synaptic Connectivity of Different Neurons onto Pyramidal Cells in a 3D Reconstruction of the Rat Hippocampus

Most existing connectomic data and ongoing efforts focus either on individual synapses (e.g., with electron microscopy) or on regional connectivity (tract tracing). An individual pyramidal cell (PC) extends thousands of synapses over macroscopic distances (∼cm). The contrasting requirements of high-resolution and large field of view make it too challenging to acquire the entire synaptic connectivity for even a single typical cortical neuron. Light microscopy can image whole neuronal arbors and resolve dendritic branches. Analyzing connectivity in terms of close spatial appositions between axons and dendrites could thus bridge the opposite scales, from synaptic level to whole systems. In the mammalian cortex, structural plasticity of spines and boutons makes these “potential synapses” functionally relevant to learning capability and memory capacity. To date, however, potential synapses have only been mapped in the surrounding of a neuron and relative to its local orientation rather than in a system-level anatomical reference. Here we overcome this limitation by estimating the potential connectivity of different neurons embedded into a detailed 3D reconstruction of the rat hippocampus. Axonal and dendritic trees were oriented with respect to hippocampal cytoarchitecture according to longitudinal and transversal curvatures. We report the potential connectivity onto PC dendrites from the axons of a dentate granule cell, three CA3 PCs, one CA2 PC, and 13 CA3b interneurons. The numbers, densities, and distributions of potential synapses were analyzed in each sub-region (e.g., CA3 vs. CA1), layer (e.g., oriens vs. radiatum), and septo-temporal location (e.g., dorsal vs. ventral). The overall ratio between the numbers of actual and potential synapses was ∼0.20 for the granule and CA3 PCs. All potential connectivity patterns are strikingly dependent on the anatomical location of both pre-synaptic and post-synaptic neurons

Principal Semantic Components of Language and the Measurement of Meaning

Metric systems for semantics, or semantic cognitive maps, are allocations of words or other representations in a metric space based on their meaning. Existing methods for semantic mapping, such as Latent Semantic Analysis and Latent Dirichlet Allocation, are based on paradigms involving dissimilarity metrics. They typically do not take into account relations of antonymy and yield a large number of domain-specific semantic dimensions. Here, using a novel self-organization approach, we construct a low-dimensional, context-independent semantic map of natural language that represents simultaneously synonymy and antonymy. Emergent semantics of the map principal components are clearly identifiable: the first three correspond to the meanings of “good/bad” (valence), “calm/excited” (arousal), and “open/closed” (freedom), respectively. The semantic map is sufficiently robust to allow the automated extraction of synonyms and antonyms not originally in the dictionaries used to construct the map and to predict connotation from their coordinates. The map geometric characteristics include a limited number (∼4) of statistically significant dimensions, a bimodal distribution of the first component, increasing kurtosis of subsequent (unimodal) components, and a U-shaped maximum-spread planar projection. Both the semantic content and the main geometric features of the map are consistent between dictionaries (Microsoft Word and Princeton's WordNet), among Western languages (English, French, German, and Spanish), and with previously established psychometric measures. By defining the semantics of its dimensions, the constructed map provides a foundational metric system for the quantitative analysis of word meaning. Language can be viewed as a cumulative product of human experiences. Therefore, the extracted principal semantic dimensions may be useful to characterize the general semantic dimensions of the content of mental states. This is a fundamental step toward a universal metric system for semantics of human experiences, which is necessary for developing a rigorous science of the mind

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. Here we present the corresponding protocol to classify cellular datasets by combining data-driven unsupervised hierarchical clustering with statistical testing. These general-purpose functions are applicable to any cellular dataset that can be organized as two-dimensional matrices of numerical values, including molecular, physiological, and anatomical datasets. We demonstrate the protocol using cellular data from the Janelia MouseLight project to characterize morphological aspects of neurons.Comment: 16 pages, 13 figure

The NIF LinkOut Broker: A Web Resource to Facilitate Federated Data Integration using NCBI Identifiers

This paper describes the NIF LinkOut Broker (NLB) that has been built as part of the Neuroscience Information Framework (NIF) project. The NLB is designed to coordinate the assembly of links to neuroscience information items (e.g., experimental data, knowledge bases, and software tools) that are (1) accessible via the Web, and (2) related to entries in the National Center for Biotechnology Information’s (NCBI’s) Entrez system. The NLB collects these links from each resource and passes them to the NCBI which incorporates them into its Entrez LinkOut service. In this way, an Entrez user looking at a specific Entrez entry can LinkOut directly to related neuroscience information. The information stored in the NLB can also be utilized in other ways. A second approach, which is operational on a pilot basis, is for the NLB Web server to create dynamically its own Web page of LinkOut links for each NCBI identifier in the NLB database. This approach can allow other resources (in addition to the NCBI Entrez) to LinkOut to related neuroscience information. The paper describes the current NLB system and discusses certain design issues that arose during its implementation

Neuromantic : from semi-manual to semi-automatic reconstruction of neuron morphology

The ability to create accurate geometric models of neuronal morphology is important for understanding the role of shape in information processing. Despite a significant amount of research on automating neuron reconstructions from image stacks obtained via microscopy, in practice most data are still collected manually. This paper describes Neuromantic, an open source system for three dimensional digital tracing of neurites. Neuromantic reconstructions are comparable in quality to those of existing commercial and freeware systems while balancing speed and accuracy of manual reconstruction. The combination of semi-automatic tracing, intuitive editing, and ability of visualizing large image stacks on standard computing platforms provides a versatile tool that can help address the reconstructions availability bottleneck. Practical considerations for reducing the computational time and space requirements of the extended algorithm are also discussed

L-neuron: a modeling tool for the efficient generation and parsimonious description of dendritic morphology.

Abstract We introduce L -Neuron (www.krasnow.gmu.edu/L-Neuron), a software package for the generation and study of anatomically accurate neuronal analogs. L-Neuron is based on sets of recursive rules that parsimoniously describe dendritic geometry and topology by locally inter-correlating morphological parameters (e.g. branch diameter and length). The L-Neuron algorithm stochastically samples parameter values from experimental statistical distributions, to generate multiple, non-identical virtual neurons within various morphological classes. Such neuronal structures, described by an Lsystem/Turtle graphic formalism, can be converted in various 3D-graphic formats and/or in compartmental anatomical files to be used in electrophysiological simulation studies with modeling programs such as Genesis or Neuron

Communication Structure of Cortical Networks

Large-scale cortical networks exhibit characteristic topological properties that shape communication between brain regions and global cortical dynamics. Analysis of complex networks allows the description of connectedness, distance, clustering, and centrality that reveal different aspects of how the network's nodes communicate. Here, we focus on a novel analysis of complex walks in a series of mammalian cortical networks that model potential dynamics of information flow between individual brain regions. We introduce two new measures called absorption and driftness. Absorption is the average length of random walks between any two nodes, and takes into account all paths that may diffuse activity throughout the network. Driftness is the ratio between absorption and the corresponding shortest path length. For a given node of the network, we also define four related measurements, namely in- and out-absorption as well as in- and out-driftness, as the averages of the corresponding measures from all nodes to that node, and from that node to all nodes, respectively. We find that the cat thalamo-cortical system incorporates features of two classic network topologies, Erdös–Rényi graphs with respect to in-absorption and in-driftness, and configuration models with respect to out-absorption and out-driftness. Moreover, taken together these four measures separate the network nodes based on broad functional roles (visual, auditory, somatomotor, and frontolimbic)