79 research outputs found
Network structure determines patterns of network reorganization during adult neurogenesis
New cells are generated throughout life and integrate into the hippocampus
via the process of adult neurogenesis. Epileptogenic brain injury induces many
structural changes in the hippocampus, including the death of interneurons and
altered connectivity patterns. The pathological neurogenic niche is associated
with aberrant neurogenesis, though the role of the network-level changes in
development of epilepsy is not well understood. In this paper, we use
computational simulations to investigate the effect of network environment on
structural and functional outcomes of neurogenesis. We find that small-world
networks with external stimulus are able to be augmented by activity-seeking
neurons in a manner that enhances activity at the stimulated sites without
altering the network as a whole. However, when inhibition is decreased or
connectivity patterns are changed, new cells are both less responsive to
stimulus and the new cells are more likely to drive the network into bursting
dynamics. Our results suggest that network-level changes caused by
epileptogenic injury can create an environment where neurogenic reorganization
can induce or intensify epileptic dynamics and abnormal integration of new
cells.Comment: 28 pages, 10 figure
From network structure to network reorganization: implications for adult neurogenesis
Networks can be dynamical systems that undergo functional and structural reorganization. One example of such a process is adult hippocampal neurogenesis, in which new cells are continuously born and incorporate into the existing network of the dentate gyrus region of the hippocampus. Many of these introduced cells mature and become indistinguishable from established neurons, joining the existing network. Activity in the network environment is known to promote birth, survival and incorporation of new cells. However, after epileptogenic injury, changes to the connectivity structure around the neurogenic niche are known to correlate with aberrant neurogenesis. The possible role of network-level changes in the development of epilepsy is not well understood. In this paper, we use a computational model to investigate how the structural and functional outcomes of network reorganization, driven by addition of new cells during neurogenesis, depend on the original network structure. We find that there is a stable network topology that allows the network to incorporate new neurons in a manner that enhances activity of the persistently active region, but maintains global network properties. In networks having other connectivity structures, new cells can greatly alter the distribution of firing activity and destroy the initial activity patterns. We thus find that new cells are able to provide focused enhancement of network only for small-world networks with sufficient inhibition. Network-level deviations from this topology, such as those caused by epileptogenic injury, can set the network down a path that develops toward pathological dynamics and aberrant structural integration of new cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85406/1/ph10_4_046008.pd
Organization of the Drosophila larval visual circuit
Visual systems transduce, process and transmit light-dependent environmental cues. Computation of visual features depends on the types of photoreceptor neurons (PR) present, the organization of the eye and the wiring of the underlying neural circuit. Here, we describe the circuit architecture of the visual system of Drosophila larvae by mapping the synaptic wiring diagram and neurotransmitters. By contacting different targets, the two larval PR-subtypes create parallel circuits potentially underlying the computation of absolute light intensity and temporal light changes already within this first visual processing center. Locally processed visual information then signals via dedicated projection interneurons to higher brain areas including the lateral horn and mushroom body. The stratified structure of the LON suggests common organizational principles with the adult fly and vertebrate visual systems. The complete synaptic wiring diagram of the LON paves the way to understanding how circuits with reduced numerical complexity control wide ranges of behaviors
Synaptic Cleft Segmentation in Non-Isotropic Volume Electron Microscopy of the Complete Drosophila Brain
Neural circuit reconstruction at single synapse resolution is increasingly
recognized as crucially important to decipher the function of biological
nervous systems. Volume electron microscopy in serial transmission or scanning
mode has been demonstrated to provide the necessary resolution to segment or
trace all neurites and to annotate all synaptic connections.
Automatic annotation of synaptic connections has been done successfully in
near isotropic electron microscopy of vertebrate model organisms. Results on
non-isotropic data in insect models, however, are not yet on par with human
annotation.
We designed a new 3D-U-Net architecture to optimally represent isotropic
fields of view in non-isotropic data. We used regression on a signed distance
transform of manually annotated synaptic clefts of the CREMI challenge dataset
to train this model and observed significant improvement over the state of the
art.
We developed open source software for optimized parallel prediction on very
large volumetric datasets and applied our model to predict synaptic clefts in a
50 tera-voxels dataset of the complete Drosophila brain. Our model generalizes
well to areas far away from where training data was available
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Conserved neural circuit structure across Drosophila larval development revealed by comparative connectomics.
During postembryonic development, the nervous system must adapt to a growing body. How changes in neuronal structure and connectivity contribute to the maintenance of appropriate circuit function remains unclear. Previously , we measured the cellular neuroanatomy underlying synaptic connectivity in Drosophila (Schneider-Mizell et al., 2016). Here, we examined how neuronal morphology and connectivity change between first instar and third instar larval stages using serial section electron microscopy. We reconstructed nociceptive circuits in a larva of each stage and found consistent topographically arranged connectivity between identified neurons. Five-fold increases in each size, number of terminal dendritic branches, and total number of synaptic inputs were accompanied by cell type-specific connectivity changes that preserved the fraction of total synaptic input associated with each pre-synaptic partner. We propose that precise patterns of structural growth act to conserve the computational function of a circuit, for example determining the location of a dangerous stimulus
Quantitative neuroanatomy for connectomics in Drosophila
Neuronal circuit mapping using electron microscopy demands laborious proofreading or reconciliation of multiple independent reconstructions. Here, we describe new methods to apply quantitative arbor and network context to iteratively proofread and reconstruct circuits and create anatomically enriched wiring diagrams. We measured the morphological underpinnings of connectivity in new and existing reconstructions of Drosophila sensorimotor (larva) and visual (adult) systems. Synaptic inputs were preferentially located on numerous small, microtubule-free 'twigs' which branch off a single microtubule-containing 'backbone'. Omission of individual twigs accounted for 96% of errors. However, the synapses of highly connected neurons were distributed across multiple twigs. Thus, the robustness of a strong connection to detailed twig anatomy was associated with robustness to reconstruction error. By comparing iterative reconstruction to the consensus of multiple reconstructions, we show that our method overcomes the need for redundant effort through the discovery and application of relationships between cellular neuroanatomy and synaptic connectivity.Publisher PDFPeer reviewe
Pattern Formation of Glioma Cells: Effects of Adhesion
We investigate clustering of malignant glioma cells. \emph{In vitro}
experiments in collagen gels identified a cell line that formed clusters in a
region of low cell density, whereas a very similar cell line (which lacks an
important mutation) did not cluster significantly. We hypothesize that the
mutation affects the strength of cell-cell adhesion. We investigate this effect
in a new experiment, which follows the clustering dynamics of glioma cells on a
surface. We interpret our results in terms of a stochastic model and identify
two mechanisms of clustering. First, there is a critical value of the strength
of adhesion; above the threshold, large clusters grow from a homogeneous
suspension of cells; below it, the system remains homogeneous, similarly to the
ordinary phase separation. Second, when cells form a cluster, we have evidence
that they increase their proliferation rate. We have successfully reproduced
the experimental findings and found that both mechanisms are crucial for
cluster formation and growth.Comment: 6 pages, 6 figure
The role of cell-cell adhesion in wound healing
We present a stochastic model which describes fronts of cells invading a
wound. In the model cells can move, proliferate, and experience cell-cell
adhesion. We find several qualitatively different regimes of front motion and
analyze the transitions between them. Above a critical value of adhesion and
for small proliferation large isolated clusters are formed ahead of the front.
This is mapped onto the well-known ferromagnetic phase transition in the Ising
model. For large adhesion, and larger proliferation the clusters become
connected (at some fixed time). For adhesion below the critical value the
results are similar to our previous work which neglected adhesion. The results
are compared with experiments, and possible directions of future work are
proposed.Comment: to appear in Journal of Statistical Physic
Synaptic transmission parallels neuromodulation in a central food-intake circuit
NeuromedinU is a potent regulator of food intake and activity in mammals. In Drosophila, neurons producing the homologous neuropeptide hugin regulate feeding and locomotion in a similar manner. Here, we use EM-based reconstruction to generate the entire connectome of hugin-producing neurons in the Drosophila larval CNS. We demonstrate that hugin neurons use synaptic transmission in addition to peptidergic neuromodulation and identify acetylcholine as a key transmitter. Hugin neuropeptide and acetylcholine are both necessary for the regulatory effect on feeding. We further show that subtypes of hugin neurons connect chemosensory to endocrine system by combinations of synaptic and peptide-receptor connections. Targets include endocrine neurons producing DH44, a CRH-like peptide, and insulin-like peptides. Homologs of these peptides are likewise downstream of neuromedinU, revealing striking parallels in flies and mammals. We propose that hugin neurons are part of an ancient physiological control system that has been conserved at functional and molecular level.SFB 645 and 704, DFG Cluster of Excellence ImmunoSensation, DFG grant PA 787, HHMI Janeli
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