Local growth rules give rise to a change in the number of axonal and dendritic elements, which is crucial for network repair.

<p>Net changes are measured as loss or gain in A) axonal and B) dendritic elements on excitatory neurons between two time steps divided by the initial number of synaptic elements before the lesion. Also shown are the average number of synaptic elements per excitatory neuron. C) Total number of excitatory synapses impinging on excitatory neurons in the peri-LPZ, in the border and in the center of the LPZ. D) Increase in average electrical activity (represented by calcium concentration) over time of all neurons in the peri-LPZ, in the border and in the center of the LPZ. All measurements for the peri-LPZ are labeled green, for the border orange, for the center blue and for controls brown. All measurements are averaged over runs; error bars: SD. Bars in (A) indicate the early, middle and late phase after lesion.</p

Network repair is not obtained if the minimum activity required for the formation of dendritic elements is higher than the activity inside the LPZ after the lesion.

<p>A) In this scenario with , new synaptic connections impinging on neurons in the LPZ are formed only transiently in the early phase after the lesion when the activity of some neurons momentarily exceeds . New connections are removed over time and even old connections are pruned. B) Activity in the LPZ decreases to a minimum level over time. Cf. <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003259#pcbi-1003259-g003" target="_blank">Fig. 3</a> for color code.</p

Whether neurons in large LPZs recover depends on the growth parameters and .

<p>A) Network repair of large LPZs does not occur for low and high , although some network reorganization takes place in the peri-LPZ and the border of the LPZ. B) Even in large LPZs neurons can completely recover if both and are low and the remaining activity in the LPZ allows axonal and dendritic elements to increase in number. Bars next to the top right panel indicate the size and position of the LPZ (orange and blue) and the peri-LPZ (green) relative to the entire network. Total number of neurons (excitatory and inhibitory): LPZ: 328 neurons; peri-LPZ: 72 neurons.</p

Different course of network repair for low and .

<p>A) Network repair is mainly due to the massive formation of new recurrent connections in the border and the center of the LPZ, while ingrowing connections from the peri-LPZ into the LPZ are rare. Recurrent connections in the border are established first followed by recurrent connections from and within the center. The timing depends only on the initial activity levels rather than on cooperative effects between different areas. B) Initially, the activity is slightly higher in the border than in the center due to normal (non-deprived) activity spreading from the peri-LPZ into the border. Cf. <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003259#pcbi-1003259-g003" target="_blank">Fig. 3</a> for color code.</p

No functional network reorganization in terms of remapping of input representations occurs for the case with , and the case with , .

<p>While the first case (A) is trivial because the neurons do not recover at all, the second case (B) is in so far remarkable that rewiring brings the activity back to the high set-point but does not give rise to functional remapping. Even in the late phase, the neurons in the LPZ, apart from a few neurons at the rim, do not become responsive to adjacent input. Cf. <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003259#pcbi-1003259-g008" target="_blank">Fig. 8</a> for color code. Note the color gradients from top to the bottom for all six columns of the three panels in A and B.</p

The outcome of network reorganization depends on the morphological response properties of individual neurons.

<p>The parametes and indicate the minimum average electrical activity individual neurons need to form axonal and dendritic elements, respectively. Experimental data is based on <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003259#pcbi.1003259-Keck1" target="_blank">[10]</a>, . Kohonen model according to <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003259#pcbi.1003259-Kohonen1" target="_blank">[89]</a>, <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003259#pcbi.1003259-Kohonen2" target="_blank">[90]</a>. Only for high, low, the model matches experimental data (cf. third and fourth row).</p

Network rewiring in the model leads to a sequential increase in electrical activity from the border to the center of the LPZ.

<p>A) Color-labeled are those synaptic connections that are newly formed after the lesion and impinge on neurons anywhere in the LPZ. Pre-existing and other connections are in gray, covering almost the entire background. Connections originating from neurons in the peri-LPZ are labeled green, from the border of the LPZ yellow and from the center blue. In the early phase, new connections are mainly formed from the peri-LPZ to the border of the LPZ. Due to fluctuations in activity, transient connections may also occur in the border or the center but usually disappear again later. In the middle phase, connections are formed from the border to the center, and finally in the late phase connections are added that originate from the center. B) In the early phase, new connections raise the activity in the border of the LPZ and subsequently in the center. Depending on the size of the LPZ, neurons in the center may fail to recover. Activities of individual neurons are interpolated to show the spatial distribution of activity in the LPZ and peri-LPZ. A) and B) are close-ups of the combined area of the LPZ and peri-LPZ. The relative size of the LPZ (border: orange; center: blue) and the peri-LPZ (green) to the entire network (gray) is indicated by the vertical and horizontal bars next to the upper right panel. Total number of neurons (excitatory and inhibitory): LPZ: 62 neurons; peri-LPZ: 71 neurons.</p

Schematic figure showing how structural plasticity in the model gives rise to functional network reorganization.

<p>New horizontal connections form between neurons in the peri-LPZ and the border of the LPZ as well as between the border and the center of the LPZ. In the model, these new synapses are the source for functional reorganization comparable to cortical retinotopic remapping. A) Network before lesion. Colors indicate spatial locations in an input layer like the retina (not explicitly modelled) and the strongest neuronal response in the model network or the primary visual cortex. Vertical input from the eye is in black, horizontal recurrent connections are in gray. Linewidth indicates the number of synapses. B) Black bar indicates loss of input. Vertical input to this area is permanently removed (dashed arrow lines). Silent neurons in the LPZ early after the lesion are labeled black. C) Additional synapses are formed at the rim of the LPZ (bold black arrows) in the middle phase after the lesion. Due to additional horizontal synapses, neurons in the border become active in response to adjacent input representation (blue and red). D) Late after the lesion, additional synapses from the border to the center contribute to the activation of center neurons, which now also become sensitive to adjacent representations (blue and red).</p

The dynamic changes in dendritic elements in the <i>structural plasticity model</i> show remarkable similarities to the spine dynamics in the visual cortex of mice after focal retinal lesions.

<p>The figure shows the survival fraction rates, accumulative addition rates and turnover rates of dendritic elements and dendritic spines on excitatory neurons A) in the model and B) in the experiment (experimental data in B reprinted by permission from Macmillan Publishers Ltd: Nature Neuroscience: Keck T et al. (2008) Massive restructuring of neuronal circuits during functional reorganization of adult visual cortex. Nat Neurosci 11:1162–1167, copyright 2008). Error bars in A) SD and in B) (experimental data:) SEM with center of LPZ: cells; border of LPZ: cells; control: cells. Color code: center of the LPZ: blue; border of the LPZ: orange; control: brown.</p

The model shows a significant overshoot in axonal elements on excitatory neurons over time following a lesion, as compared with the control situation without a lesion.

<p>A) The overshoot in the model is caused by axonal elements from neurons in the peri-LPZ (green line; brown: control). All measurements are averaged over runs; error bars: SD. B) Although the available experimental data is very limited, there are two examples from an anterograde tracer study (labeling neurons in the peri-LPZ and measuring windows in the LPZ) in monkeys after focal retinal lesions that show a clear overshoot in axonal bouton densities of excitatory neurons. Green squares indicate points of measurement. Modified from <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003259#pcbi.1003259-Yamahachi1" target="_blank">[13]</a>.</p