Dataset Information

Network structure implied by initial axon outgrowth in rodent cortex: empirical measurement and models.

ABSTRACT: The developmental mechanisms by which the network organization of the adult cortex is established are incompletely understood. Here we report on empirical data on the development of connections in hamster isocortex and use these data to parameterize a network model of early cortical connectivity. Using anterograde tracers at a series of postnatal ages, we investigate the growth of connections in the early cortical sheet and systematically map initial axon extension from sites in anterior (motor), middle (somatosensory) and posterior (visual) cortex. As a general rule, developing axons extend from all sites to cover relatively large portions of the cortical field that include multiple cortical areas. From all sites, outgrowth is anisotropic, covering a greater distance along the medial/lateral axis than along the anterior/posterior axis. These observations are summarized as 2-dimensional probability distributions of axon terminal sites over the cortical sheet. Our network model consists of nodes, representing parcels of cortex, embedded in 2-dimensional space. Network nodes are connected via directed edges, representing axons, drawn according to the empirically derived anisotropic probability distribution. The networks generated are described by a number of graph theoretic measurements including graph efficiency, node betweenness centrality and average shortest path length. To determine if connectional anisotropy helps reduce the total volume occupied by axons, we define and measure a simple metric for the extra volume required by axons crossing. We investigate the impact of different levels of anisotropy on network structure and volume. The empirically observed level of anisotropy suggests a good trade-off between volume reduction and maintenance of both network efficiency and robustness. Future work will test the model's predictions for connectivity in larger cortices to gain insight into how the regulation of axonal outgrowth may have evolved to achieve efficient and economical connectivity in larger brains.

SUBMITTER: Cahalane DJ

PROVIDER: S-EPMC3019165 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Network structure implied by initial axon outgrowth in rodent cortex: empirical measurement and models.

Cahalane Diarmuid J DJ Clancy Barbara B Kingsbury Marcy A MA Graf Ethan E Sporns Olaf O Finlay Barbara L BL

PloS one 20110111 1

The developmental mechanisms by which the network organization of the adult cortex is established are incompletely understood. Here we report on empirical data on the development of connections in hamster isocortex and use these data to parameterize a network model of early cortical connectivity. Using anterograde tracers at a series of postnatal ages, we investigate the growth of connections in the early cortical sheet and systematically map initial axon extension from sites in anterior (motor) ...[more]

PMID: 21264302

Similar Datasets

Project description:The microdomain that orchestrates action potential initiation in neurons is the axon initial segment (AIS). It has long been considered to be a rather homogeneous domain at the very proximal axon hillock with relatively stable length, particularly in cortical pyramidal cells. However, studies in other brain regions paint a different picture. In hippocampal CA1, up to 50% of axons emerge from basal dendrites. Further, in about 30% of thick-tufted layer V pyramidal neurons in rat somatosensory cortex, axons have a dendritic origin. Consequently, the AIS is separated from the soma. Recent in vitro and in vivo studies have shown that cellular excitability is a function of AIS length/position and somatodendritic morphology, undermining a potentially significant impact of AIS heterogeneity for neuronal function. We therefore investigated neocortical axon morphology and AIS composition, hypothesizing that the initial observation of seemingly homogeneous AIS is inadequate and needs to take into account neuronal cell types. Here, we biolistically transfected cortical neurons in organotypic cultures to visualize the entire neuron and classify cell types in combination with immunolabeling against AIS markers. Using confocal microscopy and morphometric analysis, we investigated axon origin, AIS position, length, diameter as well as distance to the soma. We find a substantial AIS heterogeneity in visual cortical neurons, classified into three groups: (I) axons with somatic origin with proximal AIS at the axon hillock; (II) axons with somatic origin with distal AIS, with a discernible gap between the AIS and the soma; and (III) axons with dendritic origin (axon-carrying dendrite cell, AcD cell) and an AIS either starting directly at the axon origin or more distal to that point. Pyramidal cells have significantly longer AIS than interneurons. Interneurons with vertical columnar axonal projections have significantly more distal AIS locations than all other cells with their prevailing phenotype as an AcD cell. In contrast, neurons with perisomatic terminations display most often an axon originating from the soma. Our data contribute to the emerging understanding that AIS morphology is highly variable, and potentially a function of the cell type.

Project description:Cortical networks are shaped by sensory experience and are most susceptible to modifications during critical periods characterized by enhanced plasticity at the structural and functional level. A system particularly well-studied in this context is the mammalian visual system. Plasticity has been documented for the somatodendritic compartment of neurons in detail. A neuronal microdomain not yet studied in this context is the axon initial segment (AIS) located at the proximal axon segment. It is a specific electrogenic axonal domain and the site of action potential (AP) generation. Recent studies showed that structure and function of the AIS can be dynamically regulated. Here we hypothesize that the AIS shows a dynamic regulation during maturation of the visual cortex. We therefore analyzed AIS length development from embryonic day (E) 12.5 to adulthood in mice. A tri-phasic time course of AIS length remodeling during development was observed. AIS first appeared at E14.5 and increased in length throughout the postnatal period to a peak between postnatal day (P) 10 to P15 (eyes open P13-14). Then, AIS length was reduced significantly around the beginning of the critical period for ocular dominance plasticity (CP, P21). Shortest AIS were observed at the peak of the CP (P28), followed by a moderate elongation toward the end of the CP (P35). To test if the dynamic maturation of the AIS is influenced by eye opening (onset of activity), animals were deprived of visual input before and during the CP. Deprivation for 1 week prior to eye opening did not affect AIS length development. However, deprivation from P0 to 28 and P14 to 28 resulted in AIS length distribution similar to the peak at P15. In other words, deprivation from birth prevents the transient shortening of the AIS and maintains an immature AIS length. These results are the first to suggest a dynamic maturation of the AIS in cortical neurons and point to novel mechanisms in the development of neuronal excitability.

Project description:BackgroundUsing multipollutant models to understand combined health effects of exposure to multiple pollutants is becoming more common. However, complex relationships between pollutants and differing degrees of exposure error across pollutants can make health effect estimates from multipollutant models difficult to interpret.ObjectivesWe aimed to quantify relationships between multiple pollutants and their associated exposure errors across metrics of exposure and to use empirical values to evaluate potential attenuation of coefficients in epidemiologic models.MethodsWe used three daily exposure metrics (central-site measurements, air quality model estimates, and population exposure model estimates) for 193 ZIP codes in the Atlanta, Georgia, metropolitan area from 1999 through 2002 for PM2.5 and its components (EC and SO4), as well as O3, CO, and NOx, to construct three types of exposure error: δspatial (comparing air quality model estimates to central-site measurements), δpopulation (comparing population exposure model estimates to air quality model estimates), and δtotal (comparing population exposure model estimates to central-site measurements). We compared exposure metrics and exposure errors within and across pollutants and derived attenuation factors (ratio of observed to true coefficient for pollutant of interest) for single- and bipollutant model coefficients.ResultsPollutant concentrations and their exposure errors were moderately to highly correlated (typically, > 0.5), especially for CO, NOx, and EC (i.e., "local" pollutants); correlations differed across exposure metrics and types of exposure error. Spatial variability was evident, with variance of exposure error for local pollutants ranging from 0.25 to 0.83 for δspatial and δtotal. The attenuation of model coefficients in single- and bipollutant epidemiologic models relative to the true value differed across types of exposure error, pollutants, and space.ConclusionsUnder a classical exposure-error framework, attenuation may be substantial for local pollutants as a result of δspatial and δtotal with true coefficients reduced by a factor typically < 0.6 (results varied for δpopulation and regional pollutants).

Dataset Information

Network structure implied by initial axon outgrowth in rodent cortex: empirical measurement and models.

Publications

Network structure implied by initial axon outgrowth in rodent cortex: empirical measurement and models.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets