Reorganization of columnar architecture in the growing visual cortex

Many cortical areas increase in size considerably during postnatal development, progressively displacing neuronal cell bodies from each other. At present, little is known about how cortical growth affects the development of neuronal circuits. Here, in acute and chronic experiments, we study the layout of ocular dominance (OD) columns in cat primary visual cortex (V1) during a period of substantial postnatal growth. We find that despite a considerable size increase of V1, the spacing between columns is largely preserved. In contrast, their spatial arrangement changes systematically over this period. While in young animals columns are more band-like, layouts become more isotropic in mature animals. We propose a novel mechanism of growth-induced reorganization that is based on the `zigzag instability', a dynamical instability observed in several inanimate pattern forming systems. We argue that this mechanism is inherent to a wide class of models for the activity-dependent formation of OD columns. Analyzing one member of this class, the Elastic Network model, we show that this mechanism can account for the preservation of column spacing and the specific mode of reorganization of OD columns that we observe. We conclude that neurons systematically shift their selectivities during normal development and that this reorganization is induced by the cortical expansion during growth. Our work suggests that cortical circuits remain plastic for an extended period in development in order to facilitate the modification of neuronal circuits to adjust for cortical growth.Comment: 8+13 pages, 4+8 figures, paper + supplementary materia

How Morphological Constraints Affect Axonal Polarity in Mouse Neurons

Neuronal differentiation is under the tight control of both biochemical and physical information arising from neighboring cells and micro-environment. Here we wished to assay how external geometrical constraints applied to the cell body and/or the neurites of hippocampal neurons may modulate axonal polarization in vitro. Through the use of a panel of non-specific poly-L-lysine micropatterns, we manipulated the neuronal shape. By applying geometrical constraints on the cell body we provided evidence that centrosome location was not predictive of axonal polarization but rather follows axonal fate. When the geometrical constraints were applied to the neurites trajectories we demonstrated that axonal specification was inhibited by curved lines. Altogether these results indicated that intrinsic mechanical tensions occur during neuritic growth and that maximal tension was developed by the axon and expressed on straight trajectories. The strong inhibitory effect of curved lines on axon specification was further demonstrated by their ability to prevent formation of multiple axons normally induced by cytochalasin or taxol treatments. Finally we provided evidence that microtubules were involved in the tension-mediated axonal polarization, acting as curvature sensors during neuronal differentiation. Thus, biomechanics coupled to physical constraints might be the first level of regulation during neuronal development, primary to biochemical and guidance regulations

Emergence of small-world anatomical networks in self-organizing clustered neuronal cultures

In vitro primary cultures of dissociated invertebrate neurons from locust ganglia are used to experimentally investigate the morphological evolution of assemblies of living neurons, as they self-organize from collections of separated cells into elaborated, clustered, networks. At all the different stages of the culture's development, identification of neurons' and neurites' location by means of a dedicated software allows to ultimately extract an adjacency matrix from each image of the culture. In turn, a systematic statistical analysis of a group of topological observables grants us the possibility of quantifying and tracking the progression of the main network's characteristics during the self-organization process of the culture. Our results point to the existence of a particular state corresponding to a small-world network configuration, in which several relevant graph's micro- and meso-scale properties emerge. Finally, we identify the main physical processes ruling the culture's morphological transformations, and embed them into a simplified growth model qualitatively reproducing the overall set of experimental observations. © 2014 de Santos-Sierra et al

Mechanical tension contributes to clustering of neurotransmitter vesicles at presynaptic terminals

Memory and learning in animals are mediated by neurotransmitters that are released from vesicles clustered at the synapse. As a synapse is used more frequently, its neurotransmission efficiency increases, partly because of increased vesicle clustering in the presynaptic neuron. Vesicle clustering has been believed to result primarily from biochemical signaling processes that require the connectivity of the presynaptic terminal with the cell body, the central nervous system, and the postsynaptic cell. Our in vivo experiments on the embryonic Drosophila nervous system show that vesicle clustering at the neuromuscular presynaptic terminal depends on mechanical tension within the axons. Vesicle clustering vanishes upon severing the axon from the cell body, but is restored when mechanical tension is applied to the severed end of the axon. Clustering increases when intact axons are stretched mechanically by pulling the postsynaptic muscle. Using micro mechanical force sensors, we find that embryonic axons that have formed neuromuscular junctions maintain a rest tension of ≈1 nanonewton. If the rest tension is perturbed mechanically, axons restore the rest tension either by relaxing or by contracting over a period of ≈15 min. Our results suggest that neuromuscular synapses employ mechanical tension as a signal to modulate vesicle accumulation and synaptic plasticity