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Review
. 2015 Jun;21(3):241-54.
doi: 10.1177/1073858414540216. Epub 2014 Jun 27.

Quantitative investigations of axonal and dendritic arbors: development, structure, function, and pathology

Affiliations
Review

Quantitative investigations of axonal and dendritic arbors: development, structure, function, and pathology

Ruchi Parekh et al. Neuroscientist. 2015 Jun.

Abstract

The branching structures of neurons are a long-standing focus of neuroscience. Axonal and dendritic morphology affect synaptic signaling, integration, and connectivity, and their diversity reflects the computational specialization of neural circuits. Altered neuronal morphology accompanies functional changes during development, experience, aging, and disease. Technological improvements continuously accelerate high-throughput tissue processing, image acquisition, and morphological reconstruction. Digital reconstructions of neuronal morphologies allow for complex quantitative analyses that are unattainable from raw images or two-dimensional tracings. Furthermore, digitized morphologies enable computational modeling of biophysically realistic neuronal dynamics. Additionally, reconstructions generated to address specific scientific questions have the potential for continued investigations beyond the original reason for their acquisition. Facilitating multiple reuse are repositories like NeuroMorpho.Org, which ease the sharing of reconstructions. Here, we review selected scientific literature reporting the reconstruction of axonal or dendritic morphology with diverse goals including establishment of neuronal identity, examination of physiological properties, and quantification of developmental or pathological changes. These reconstructions, deposited in NeuroMorpho.Org, have since been used by other investigators in additional research, of which we highlight representative examples. This cycle of data generation, analysis, sharing, and reuse reveals the vast potential of digital reconstructions in quantitative investigations of neuronal morphology.

Keywords: data sharing; database; neuron morphology; quantitative analysis; three-dimensional reconstructions.

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Figures

Figure 1
Figure 1. Structural diversity in dendrites (black) and axons (red)
The species, brain region, and reported neuron type of representative reconstructions from NeuroMorpho.Org (numbers in parenthesis indicate the corresponding unique identifier “NMO_ID” in the database); scale bars: 100 μm. A) Proechimys, hippocampus, pyramidal-like (7254); B) Rabbit, retina, amacrine (765); C) Rat, hippocampus, von Economo (930); D) Goldfish, optic nerve, sensory (6897); E) Drosophila, peripheral nervous system, pyramidal (7046); F) Zebrafish, spinal cord, motoneuron (9367); G) Elephant, neocortex, motoneuron (6239); H) Frog, spinal cord, motoneuron (7289); I) Mouse, neocortex, parvalbumin containing (8508); J) Monkey, neocortex, sensory interneuron (1869); K) Cricket, cercal sensory system, neurogliaform (4594); L) Turtle, spinal cord, motoneuron (7291); M) C. elegans, somatic nervous system, sensory (9857); N) Cat, neocortex, pyramidal (856); O) Chicken, brainstem, bipolar (8909); P) Human, neocortex, basket (1078); Q) Spiny lobster, stomatogastric ganglion, retinotectal (6634); R) Salamander, retina, ganglion (770); S) Guinea-pig, hippocampus, pyramidal (7904).
Figure 2
Figure 2. Examples of primary discoveries made with digital reconstructions
A) Diversity of excitatory neurons in layer 6b of the rat barrel cortex from the Feldmeyer archive of NeuroMorpho.Org (adapted from Marx and Feldmeyer 2013). B) Morphological and electrophysiological characterization of newly identified pyramidal neurons from the Staiger archive (adapted from Schubert and others 2006). The left photomicrograph of the native coronal slice is superimposed to the somatodendritic reconstruction of the recorded neuron. The color-coded topographic map represents the delay between glutamate uncaging and activity onset in the recorded cell, separating likely direct and indirect connections. The larger rectangular and smaller rounded black frames mark the extent of the investigated cortical area and the layer IV barrels, respectively (scale bar: 100 μm). The inset illustrates the laminar and columnar organization. The top right voltage recording corresponds to the firing pattern upon depolarizing current injection of the same neuron at the resting potential (Vrmp). The traces below are membrane potential recordings at the given holding potential (Vh) obtained after glutamate uncaging (yellow arrows) at the positions indicated by the circled numbers. C) Distribution of vestibulospinal synapses on ipsilateral splenius motoneurons in an adult cat spinal cord from the Rose archive (adapted from Grande and others 2010).
Figure 3
Figure 3. Availability of reconstructed neuronal morphology in NeuroMorpho.Org
A) At the introductory release in August 2006, the repository contained ~1,000 reconstructions and 21 archives. Subsequent version releases show a steady increase in the content of the repository. At the May 2014 release (v5.7), the total number of reconstructions is 11,335 from 144 archives. B) With increased data content, the numbers of represented species, brain regions, and cell types have also steadily grown since over the years.
Figure 4
Figure 4. Data download from NeuroMorpho.Org
Reconstructions downloaded from NeuroMorpho.Org across three categories: A) species, B) brain regions, and C) cell types. The abscissa refers to the time of download, thus 2006 only counts for its last 5 months since the first public (pre-) release in August. Within every entry of each category, downloads in one year are normalized by the total number of downloads for that same entry over the entire 2006–2014 period. The absolute numbers of total downloads are reported for each entry in parentheses.
Figure 5
Figure 5. Categories of publications that contributed to (primary) and utilized data from (secondary) NeuroMorpho.Org
A total of 307 publications, divided in primary (dark grey) and secondary (light grey) discovery, were categorized based on their primary focus as anatomical, physiological, computational or others. The colored dashed lines reflect the “added impact” or percentage scientific gain expressed as the equivalent number of secondary publications enabled by data shared from a given category.
Figure 6
Figure 6. Examples of secondary discoveries made with reconstructions downloaded from NeuroMorpho.Org
A) Structural design principle describing an inverse relationship between branching complexity and total arbor area in all neurons (adapted from Teeter and Stevens 2011). These data illustrate the case of relatively flat trees from retinal ganglion cells (RGC) and Purkinje cells. B) Space occupancy, dendritic overlap, and orientation of pyramidal cells in the rat hippocampus (Ropireddy and others 2012). The fully reconstructed axon of a single pyramidal cell (green) is embedded in the volumetric rendering of a digital reconstruction of the hippocampal tissue. In the left inset, the reconstructed dendritic trees of pyramidal cells from NeuroMorpho.Org are embedded in the same space. C) Neuron models with stochastically gated, identically distributed ion channels in distinct morphologies, exemplified on the left. On the right, the average standard deviations of the simulated membrane potentials are plotted for each morphological type as a function of increasing distance along the dendrite from the soma (adapted from Cannon and others 2010).

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