Neural network architecture of a mammalian brain.

Connectomics research is making rapid advances, although models revealing general principles of connectional architecture are far from complete. Our analysis of 10 published connection reports indicates that the adult rat brain interregional connectome has about 76,940 of a possible 623,310 axonal connections between its 790 gray matter regions mapped in a reference atlas, equating to a network density of 12.3%.

Network architecture of intrinsic connectivity in a mammalian spinal cord (the central nervous system's caudal sector).

The vertebrate spinal cord (SP) is the long, thin extension of the brain forming the central nervous system's caudal sector. Functionally, the SP directly mediates motor and somatic sensory interactions with most parts of the body except the face, and it is the preferred model for analyzing relatively simple reflex behaviors. Here, we analyze the organization of axonal connections between the 50 gray matter regions forming the bilaterally symmetric rat SP.

Intrinsic circuitry of the rhombicbrain (central nervous system's intermediate sector) in a mammal.

The rhombicbrain (rhombencephalon or intermediate sector) is the vertebrate central nervous system part between the forebrain-midbrain (rostral sector) and spinal cord (caudal sector), and it has three main divisions: pons, cerebellum, and medulla. Using a data-driven approach, here we examine intrinsic rhombicbrain (intrarhombicbrain) network architecture that in rat consists of 52,670 possible axonal connections between 230 gray matter regions (115 bilaterally symmetrical pairs). Our analysis indicates that only 8,089 (15.

Structure-function subsystem model and computational lesions of the central nervous system's rostral sector (forebrain and midbrain).

The craniote central nervous system has been divided into rostral, intermediate, and caudal sectors, with the rostral sector containing the vertebrate forebrain and midbrain. Here, network science tools were used to create and analyze a rat hierarchical structure-function subsystem model of intrarostral sector neural connectivity between gray matter regions. The hierarchy has 109 bottom-level subsystems and three upper-level subsystems corresponding to voluntary behavior control, cognition, and affect; instinctive survival behaviors and homeostasis; and oculomotor control.

Subsystem macroarchitecture of the intrinsic midbrain neural network and its tectal and tegmental subnetworks.

The midbrain is the smallest of three primary vertebrate brain divisions. Here we use network science tools to reveal the global organizing principles of intramidbrain axonal circuitry before adding extrinsic connections with the remaining nervous system. Curating the experimental neuroanatomical literature yielded 17,248 connection reports for 8,742 possible connections between the 94 gray matter regions forming the right and left midbrain.

Structure-function subsystem models of female and male forebrain networks integrating cognition, affect, behavior, and bodily functions.

The forebrain is the first of three primary vertebrate brain subdivisions. Macrolevel network analysis in a mammal (rat) revealed that the 466 gray matter regions composing the right and left sides of the forebrain are interconnected by 35,738 axonal connections forming a large set of overlapping, hierarchically arranged subsystems. This hierarchy is bilaterally symmetrical and sexually dimorphic, and it was used to create a structure-function conceptual model of intraforebrain network organization.

An open access mouse brain flatmap and upgraded rat and human brain flatmaps based on current reference atlases.

Here we present a flatmap of the mouse central nervous system (CNS) (brain) and substantially enhanced flatmaps of the rat and human brain. Also included are enhanced representations of nervous system white matter tracts, ganglia, and nerves, and an enhanced series of 10 flatmaps showing different stages of rat brain development. The adult mouse and rat brain flatmaps provide layered diagrammatic representation of CNS divisions, according to their arrangement in corresponding reference atlases: Brain Maps 4.

A qualitative solution with quantitative potential for the mouse hippocampal cortex flatmap problem.

The hippocampal formation (HPF) is a focus of intense experimental investigation, particularly because of its roles in conscious memory consolidation, spatial navigation, emotion, and motivated behaviors. However, the HPF has a complex three-dimensional geometry resulting from extreme curvature of its layers, and this presents a challenge for investigators seeking to decipher hippocampal structure and function at cellular and molecular scales (neuronal circuitry, gene expression, and other properties). Previously, this problem was solved qualitatively for the rat by constructing a physical surface model of the HPF based on histological sections, and then deriving from the model a flatmap.

The network architecture of rat intrinsic interbrain (diencephalic) macroconnections.

The endbrain and interbrain form 2 great vertebrate forebrain divisions, and the interbrain is subdivided into the hypothalamus ventrally and thalamus dorsally. General organizing principles of intrainterbrain axonal circuitry were examined here at the level of gray matter regions using network analysis tools in a mammal with the most complete available dataset-before examining interbrain input-output relationships with other nervous system parts. The dataset was curated expertly from the neuroanatomical literature using experimental axonal pathway-tracing methods, and evidence from 74,242 connection reports indicates the existence of 10,836 macroconnections of the possible 49,062 macroconnections between the 222 gray matter regions forming the right and left halves of the interbrain.

The network organization of rat intrathalamic macroconnections and a comparison with other forebrain divisions.

The thalamus is 1 of 4 major divisions of the forebrain and is usually subdivided into epithalamus, dorsal thalamus, and ventral thalamus. The 39 gray matter regions comprising the large dorsal thalamus project topographically to the cerebral cortex, whereas the much smaller epithalamus (2 regions) and ventral thalamus (5 regions) characteristically project subcortically. Before analyzing extrinsic inputs and outputs of the thalamus, here, the intrinsic connections among all 46 gray matter regions of the rat thalamus on each side of the brain were expertly collated and subjected to network analysis.

A model for mapping between the human and rodent cerebral cortex.

Iterative interactions between functional brain imaging in humans and mechanistic research in other animals hold great promise for understanding and treating mental health and neurological disorders. One way to accelerate discovery in this domain is to develop a unified, widely accepted vocabulary for describing structural and functional localization in the mammalian brain. To facilitate generation of such a defined nomenclature we begun by creating a table for direct mapping between terms for describing cerebral cortex parcellation according to six schemes in human, three schemes in mouse, and two schemes in rat.

Macroscale intrinsic network architecture of the hypothalamus.

Control of multiple life-critical physiological and behavioral functions requires the hypothalamus. Here, we provide a comprehensive description and rigorous analysis of mammalian intrahypothalamic network architecture. To achieve this at the gray matter region (macroscale) level, macroscale connection (macroconnection) data for the rat hypothalamus were extracted from the primary literature.

A Network Explanation of Alzheimer's Regional Vulnerability.

Studies in patients and mouse models have pinpointed a precise zone in the cerebral cortex selectively vulnerable to the earliest stages of Alzheimer's disease (AD): the borderzone covering the entorhinal and perirhinal cortical areas. An independent series of studies has revealed that this entorhinal-perirhinal borderzone is a central cortical hub, with a distinct connectivity pattern across the cerebral hemispheres. Here we develop a hypothesis that explains how this distinct network feature interacts with established pathogenic drivers of AD in explaining the disease's regional vulnerability and suggests how it acts as an anatomical source of disease spread.

Subsystem organization of axonal connections within and between the right and left cerebral cortex and cerebral nuclei (endbrain).

The endbrain (telencephalon) is at the rostral end of the central nervous system and is primarily responsible for supporting cognition and affect. Structurally, it consists of right and left cerebral hemispheres, each parceled into multiple cortical and nuclear gray matter regions. The global network organization of axonal macroconnections between the 244 regions forming the endbrain was analyzed with a multiresolution consensus clustering (MRCC) method that provides a hierarchical description of community clustering (modules or subsystems) within the network.

Brain maps 4.0-Structure of the rat brain: An open access atlas with global nervous system nomenclature ontology and flatmaps.

The fourth edition (following editions in 1992, 1998, 2004) of Brain maps: structure of the rat brain is presented here as an open access internet resource for the neuroscience community. One new feature is a set of 10 hierarchical nomenclature tables that define and describe all parts of the rat nervous system within the framework of a strictly topographic system devised previously for the human nervous system. These tables constitute a global ontology for knowledge management systems dealing with neural circuitry.

Organizing principles for the cerebral cortex network of commissural and association connections.

Cognition is supported by a network of axonal connections between gray matter regions within and between right and left cerebral cortex. Global organizing principles of this circuitry were examined with network analysis tools applied to monosynaptic association (within one side) and commissural (between sides) connections between all 77 cortical gray matter regions in each hemisphere of the rat brain. The analysis used 32,350 connection reports expertly collated from published pathway tracing experiments, and 5,394 connections of a possible 23,562 were identified, for a connection density of 23%-of which 20% (1,084) were commissural.

Network architecture of the cerebral nuclei (basal ganglia) association and commissural connectome.

The cerebral nuclei form the ventral division of the cerebral hemisphere and are thought to play an important role in neural systems controlling somatic movement and motivation. Network analysis was used to define global architectural features of intrinsic cerebral nuclei circuitry in one hemisphere (association connections) and between hemispheres (commissural connections). The analysis was based on more than 4,000 reports of histologically defined axonal connections involving all 45 gray matter regions of the rat cerebral nuclei and revealed the existence of four asymmetrically interconnected modules.

From Cajal to Connectome and Beyond.

One goal of systems neuroscience is a structure-function model of nervous system organization that would allow mechanistic linking of mind, brain, and behavior. A necessary but not sufficient foundation is a connectome, a complete matrix of structural connections between the nodes of a nervous system. Connections between two nodes can be described at four nested levels of analysis: macroconnections between gray matter regions, mesoconnections between neuron types, microconnections between individual neurons, and nanoconnections at synapses.

Commentary on: Saper CB, Loewy AD, Swanson LW, Cowan WM. (1976) Direct hypothalamo-autonomic connections. Brain Research 117:305-312.

The 1970s saw the introduction of new technologies for tracing axons both anterogradely and retrogradely. These methods allowed us to visualize fine, unmyelinated pathways for the first time, such as the hypothalamic pathways that control the autonomic nervous system. As a result, we were able to identify the paraventricular nucleus and lateral hypothalamus as the key sites that provide direct inputs to the autonomic preganglionic neurons in the medulla and spinal cord.

Golgi: Interactive Online Brain Mapping.

Golgi (http://www.usegolgi.com) is a prototype interactive brain map of the rat brain that helps researchers intuitively interact with neuroanatomy, connectomics, and cellular and chemical architecture.

Connections of the juxtaventromedial region of the lateral hypothalamic area in the male rat.

Unlabelled: Evolutionary conservation of the hypothalamus attests to its critical role in the control of fundamental behaviors. However, our knowledge of hypothalamic connections is incomplete, particularly for the lateral hypothalamic area (LHA). Here we present the results of neuronal pathway-tracing experiments to investigate connections of the LHA juxtaventromedial region, which is parceled into dorsal (LHAjvd) and ventral (LHAjvv) zones.

Architecture of the cerebral cortical association connectome underlying cognition.

Cognition presumably emerges from neural activity in the network of association connections between cortical regions that is modulated by inputs from sensory and state systems and directs voluntary behavior by outputs to the motor system. To reveal global architectural features of the cortical association connectome, network analysis was performed on >16,000 reports of histologically defined axonal connections between cortical regions in rat. The network analysis reveals an organization into four asymmetrically interconnected modules involving the entire cortex in a topographic and topologic core-shell arrangement.

BAMS2 workspace: a comprehensive and versatile neuroinformatic platform for collating and processing neuroanatomical connections.

We describe a novel neuroinformatic platform, the BAMS2 Workspace (http://brancusi1.usc.edu), designed for storing and processing information on gray matter region axonal connections.