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. A second new feature is an aligned atlas of bilateral flatmaps illustrating rat nervous system development from the neural plate stage to the adult stage, where most gray matter regions, white matter tracts, ganglia, and nerves listed in the nomenclature tables are illustrated schematically. These flatmaps are convenient for future development of online applications analogous to “Google Maps” for systems neuroscience. The third new feature is a completely revised Atlas of the rat brain in spatially aligned transverse sections that can serve as a framework for 3‐D modeling. Atlas parcellation is little changed from the preceding edition, but the nomenclature for rat is now aligned with an emerging panmammalian neuroanatomical nomenclature. All figures are presented in Adobe Illustrator vector graphics format that can be manipulated, modified, and resized as desired, and freely used with a Creative Commons license.
Key findings: The fourth edition of Brain Maps: Structure of the Rat Brain is presented as an open access, online resource for the neuroscience community. It has 10 new hierarchical nomenclature tables for all parts of the rat nervous system, a revised atlas of the brain, and a new atlas of flatmaps illustrating development of the embryonic neural plate to the adult nervous system with all its gray and white matter regions, ganglia, and nerves.
From Cajal to Connectome and Beyond Swanson, Larry W; Lichtman, Jeff W
Annual review of neuroscience,
07/2016, Letnik:
39, Številka:
1
Journal Article
Recenzirano
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. A long history of attempts to understand how the brain operates as a system began at the macrolevel in the fifth century, was revolutionized at the meso- and microlevels by Cajal and others in the late nineteenth century, and reached the nanolevel in the mid-twentieth century with the advent of electron microscopy. The greatest challenge today is extracting knowledge and understanding of nervous system structure-function architecture from vast amounts of data.
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. There is also a topographically continuous U-shaped band of cortical areas that are highly connected with each other as well as with the rest of the cortex extending through all four modules, with the temporal pole of this band (entorhinal area) having the most cortical association connections of all. These results provide a starting point for compiling a mammalian nervous system connectome that could ultimately reveal novel correlations between genome-wide association studies and connectome-wide association studies, leading to new insights into the cellular architecture supporting cognition.
Significance Connections between cerebral cortex regions are known as association connections, and neural activity in the network formed by these connections is thought to generate cognition. Network analysis of microscopic association connection data produced over the last 40 years in a small, easily studied mammal suggests a new way to describe the organization of the cortical association network. Basically, it consists of four modules with an anatomical shell–core arrangement and asymmetric connections within and between modules, implying at least partly “hardwired,” genetically determined biases of information flow through the cortical association network. The results advance the goal of achieving a global nervous system wiring diagram of connections and provide another step toward understanding the cellular architecture and mechanisms underpinning cognition.
The brain is usually described as hierarchically organized, although an alternative network model has been proposed. To help distinguish between these two fundamentally different structure-function ...hypotheses, we developed an experimental circuit-tracing strategy that can be applied to any starting point in the nervous system and then systematically expanded, and applied it to a previously obscure dorsomedial corner of the nucleus accumbens identified functionally as a "hedonic hot spot." A highly topographically organized set of connections involving expected and unexpected gray matter regions was identified that prominently features regions associated with appetite, stress, and clinical depression. These connections are arranged as a longitudinal series of circuits (closed loops). Thus, the results do not support a rigidly hierarchical model of nervous system organization but instead indicate a network model of organization. In principle, the double-coinjection circuit tracing strategy can be applied systematically to the rest of the nervous system to establish the architecture of the global structural wiring diagram, and its abstraction, the connectome.
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. The assembled dataset suggests that there are about 385 of a possible 2,450 connections between the 50 regions for a connection density of 15.7%. Multiresolution consensus cluster analysis reveals a hierarchy of structure-function subsystems in this neural network, with 4 subsystems at the top level and 12 at the bottom-level. The top-level subsystems include a) a bilateral subsystem related most clearly to somatic and autonomic motor functions and centered in the ventral horn and intermediate zone; b) a bilateral subsystem associated with general somatosensory functions and centered in the base, neck, and head of the dorsal horn; and c) a pair of unilateral, bilaterally symmetric subsystems associated with nociceptive information processing and occupying the apex of the dorsal horn. The intrinsic SP network displayed no hubs, rich club, or small-world attributes, which are common measures of global functionality. Advantages and limitations of our methodology are discussed in some detail. The present work is part of a comprehensive project to assemble and analyze the neurome of a mammalian nervous system and its interactions with the body.
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 (15.4%) of these connections exist. Multiresolution consensus cluster analysis yields a nested hierarchy model of rhombicbrain subsystems that at the top level are associated with 1) the cerebellum and vestibular nuclei, 2) orofacial-pharyngeal-visceral integration, and 3) auditory connections; the bottom level has 68 clusters, ranging in size from 2 to 11 regions. The model provides a basis for functional hypothesis development and interrogation. More granular network analyses performed on the intrinsic connectivity of individual and combined main rhombicbrain divisions (pons, cerebellum, medulla, pons + cerebellum, and pons + medulla) demonstrate the mutability of network architecture in response to the addition or subtraction of connections. Clear differences between the structure-function network architecture of the rhombicbrain and forebrain-midbrain are discussed, with a stark comparison provided by the subsystem and small-world organization of the cerebellar cortex and cerebral cortex. Future analysis of the connections within and between the forebrain-midbrain and rhombicbrain will provide a model of brain neural network architecture in a mammal.
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 community detection yielded a stable bihemispheric six-module solution, with an identical set in each hemisphere of three modules topographically forming a lateral core and medial shell arrangement of cortical regions. Functional correlations suggest the lateral module deals preferentially with environmental sensory-motor interactions and the ventromedial module deals preferentially with visceral control, affect, and short-term memory, whereas the dorsomedial module resembles the default mode network. Analysis of commissural connections revealed a set of unexpected rules to help generate hypotheses. Most notably, there is an order of magnitude more heterotopic than homotopic projections; all cortical regions send more association than commissural connections, and for each region, the latter are always a subset of the former; the number of association connections from each cortical region strongly correlates with the number of its commissural connections; and the module (dorsomedial) lying closest to the corpus callosum has the most complete set of commissural connections—and apparently the most complex function.
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. As in previous work, subsystems identified based on their coclassification as network communities are revealed as functionally related. We carried out focal perturbations of neural structural connectivity comprehensively by computationally lesioning each region of the network, and the resulting effects on the network's modular (subsystem) organization were systematically mapped and measured. The pattern of changes was found to be correlated with three structural attributes of the lesioned region: region centrality (degree, strength, and betweenness), region position in the hierarchy, and subsystem distribution of region neural outputs and inputs. As expected, greater region centrality results, on average, in stronger lesion impact and more distributed lesion effects. In addition, our analysis suggests that strongly functionally related regions, belonging to the same bottom-level subsystem, exhibit similar effects after lesioning. These similarities account for coherent patterns of disturbances that align with subsystem boundaries and propagate through the network. These systematic lesion effects and their similarity across functionally related regions are of potential interest for theoretical, experimental, and clinical studies.
Functional heterogeneity has been investigated for decades in the hippocampal region of the mammalian cerebral cortex, and evidence for vaguely defined "dorsal" and "ventral" regions is emerging. ...Direct evidence that hippocampal field CA1 displays clear regional, laminar, and pyramidal neuron differentiation is presented here, based on a systematic high-resolution analysis of a publicly accessible, genome-wide expression digital library (Allen Brain Atlas) Lein et al. (2007) Genome-wide atlas of gene expression in the adult mouse brain. Nature 445:168-176. First, genetic markers reveal distinct spatial expression domains and subdomains along the longitudinal (dorsal/septal/posterior to ventral/temporal/anterior) axis of field CA1. Second, genetic markers divide field CA1 pyramidal neurons into multiple subtypes with characteristic laminar distributions. And third, subcortical brain regions receiving axonal projections from molecularly distinct spatial domains of field CA1 display distinct global gene expression patterns, suggesting that field CA1 spatial domains may be genetically wired independently to form distinct functional networks related to cognition and emotion. Insights emerging from this genomic-anatomic approach provide a starting point for a detailed analysis of differential hippocampal structure-function organization.
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. The dataset indicated the existence of 7,982 (of 16,770 possible) intrahypothalamic macroconnections. Network analysis revealed that the intrahypothalamic macroconnection network (its macroscale subconnectome) is divided into two identical top-level subsystems (or subnetworks), each composed of two nested second-level subsystems. At the top-level, this suggests a deeply integrated network; however, regional grouping of the two second-level subsystems suggested a partial separation between control of physiological functions and behavioral functions. Furthermore, inclusion of four candidate hubs (dominant network nodes) in the second-level subsystem that is associated prominently with physiological control suggests network primacy with respect to this function. In addition, comparison of network analysis with expression of gene markers associated with inhibitory (GAD65) and excitatory (VGLUT2) neurotransmission revealed a significant positive correlation between measures of network centrality (dominance) and the inhibitory marker. We discuss these results in relation to previous understandings of hypothalamic organization and provide, and selectively interrogate, an updated hypothalamus structure–function network model to encourage future hypothesis-driven investigations of identified hypothalamic subsystems.
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