List of the different families of models developed in the present study.

<p>List of the different families of models developed in the present study.</p

Schematic representation of the strategies used to classify the dendrites and place the synapses.

<p><b>A</b>. Classification of a dendrite as proximal (PD), medial (MD) and distal (DP) based on the distance from soma up to the branching point of the dendrite (yellow line). <b>B</b>. Location of the synapses depending on the sublayer in which a dendrite section is located.</p

Scheme of the structure and topology of the network.

<p><b>A</b>. Schematic representation of network connections between granule cells (GC), basket cells (BC), hilar perforant-path associated cells (HC) and mossy cells (MC). GC synapses are indicated by black lines, BC synapses are indicated by blue lines, HC synapses are indicated by orange dashed lines and MC synapses are indicated by green lines. Mossy fiber sprouting (MFS) is indicated by a black dashed line and the perforant-path input to GC and BC is indicated by a bold black line. The segments into which the GC dendritic tree are divided are indicated in yellow (granule cell layer dendrites), orange (proximal dendrites), green (medial dendrites) and blue (distal dendrites). <b>B</b>. Positioning of the GC within the molecular layer with its four subdivisions: granular layer (GL) in blue, inner molecular layer (IML) in orange, middle molecular layer (MML) in green and outer molecular layer (OML) in blue. The figure shows that perforant-path synapses to GCs are located in OML dendrites and mossy fiber sprouting synapses to GCs are located in IML dendrites regardless of the type of dendritic segment in these layers. <b>C</b>. Schematic representation of the dentate gyrus model with control GCs. <b>D</b>. Schematic representation of the dentate gyrus model with a fraction of the control GCs replaced with cells from PILO-treated animals (in red).</p

Overall frequency of the network (total spike count over simulation time) for the different network families as a function of the proportion of newborn GCs.

<p>All cases are for 10% of mossy fiber sprouting. Each point in the graph corresponds to an average over 20 randomly generated models of the corresponding family. The different network families are indicated by different colors and their codes are the same as defined in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003601#pcbi-1003601-t002" target="_blank">Table 2</a>. <b>A.</b> Cases in which spine loss was represented by a 50% reduction in the probability of connections with newborn GCs. The MPSL1 network type only had results up to the insertion of 80% of newborn cells because the insertions of 90% and 100% of newborn GCs did not allow the maintenance of the convergence and divergence factors of the network. The error bars represent the standard error. The overall frequency is significantly different over the different proportions () and types of altered cells and spine loss inserted () and their interaction (). <b>B.</b> Cases in which spine loss was represented by a reduction of 25%, 50% and 75% in the probability of newborn GCs receiving connections. The coding is the same as in A but followed by the corresponding reduction in the probability of connection.</p

Examples of raster plots for different DG network models.

<p><b>A</b>. Response of a mature network without mossy fiber sprouting. <b>B</b>. Response of a mature network with 10% mossy fiber sprouting. <b>C</b>. Response of a mature network with 50% mossy fiber sprouting. <b>D</b>. Response of a mature network with 50% newborn control GCs without mossy fiber sprouting. <b>E</b>. Response of a mature network with 10% newborn control GCs and 10% mossy fiber sprouting. <b>F</b>. Response of a mature network with 50% newborn control GCs and 10% mossy fiber sprouting. <b>G</b>. Response of a mature network with 50% newborn PILO GCs without mossy fiber sprouting. <b>H</b>. Response of a mature network with 10% newborn PILO GCs and 10% mossy fiber sprouting. <b>I</b>. Response of a mature network with 50% newborn PILO GCs and 10% mossy fiber sprouting. <b>J</b>. Response of a mature network with 10% newborn PILO GCs with spine loss and without mossy fiber sprouting. <b>K</b>. Response of a mature network with 10% newborn PILO GCs with spine loss and 10% mossy fiber sprouting. <b>L</b>. Response of a mature network with 50% newborn PILO GCs with spine loss and 10% mossy fiber sprouting. The latter three figures for the cases with spine loss were obtained for the SL2 case.</p

Comparison of the intrinsic excitability of the mature and newborn GCs from control (YOUNG) and PILO groups.

<p>The cases for model cells without spine loss are indicated in blue and the cases for model cells with spine loss are indicated in red. <b>A</b>. Average rheobase current (measured as explained in the text) for the three model cell groups. <b>B</b>. Average number of spikes evoked by the train of synaptic-like pulses as explained in the text.</p

List of the three-dimensional GC reconstructions from neuromorpho.org used to build the mature DG model0.

<p>Regarding the newborn GC models, we used the 40 available reconstructions in <i>neuromorpho.org</i> from Arisi & Garcia-Cairasco <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003601#pcbi.1003601-Arisi1" target="_blank">[16]</a>.</p

Behavioral, Ventilatory and Thermoregulatory Responses to Hypercapnia and Hypoxia in the Wistar Audiogenic Rat (WAR) Strain

<div><p>Introduction</p><p>We investigated the behavioral, respiratory, and thermoregulatory responses elicited by acute exposure to both hypercapnic and hypoxic environments in Wistar audiogenic rats (WARs). The WAR strain represents a genetic animal model of epilepsy.</p><p>Methods</p><p>Behavioral analyses were performed using neuroethological methods, and flowcharts were constructed to illustrate behavioral findings. The body plethysmography method was used to obtain pulmonary ventilation (VE) measurements, and body temperature (Tb) measurements were taken via temperature sensors implanted in the abdominal cavities of the animals.</p><p>Results</p><p>No significant difference was observed between the WAR and Wistar control group with respect to the thermoregulatory response elicited by exposure to both acute hypercapnia and acute hypoxia (p>0.05). However, we found that the VE of WARs was attenuated relative to that of Wistar control animals during exposure to both hypercapnic (WAR: 133 ± 11% vs. Wistar: 243 ± 23%, p<0.01) and hypoxic conditions (WAR: 138 ± 8% vs. Wistar: 177 ± 8%; p<0.01). In addition, we noted that this ventilatory attenuation was followed by alterations in the behavioral responses of these animals.</p><p>Conclusions</p><p>Our results indicate that WARs, a genetic model of epilepsy, have important alterations in their ability to compensate for changes in levels of various arterial blood gasses. WARs present an attenuated ventilatory response to an increased PaCO₂ or decreased PaO_2, coupled to behavioral changes, which make them a suitable model to further study respiratory risks associated to epilepsy.</p></div

ECG recordings illustrating ectopic beats (arrows) in 3 different WAR studied at 1 year of age.

<p>(A) One isolated ectopic beat, (B) two ectopic beats from distinct ventricular origins and (C) a period of bigeminy.</p

Changes in body temperature after Hypercapnia.

<p>Time-course of body temperature (Tb, ΔC, A) changes during 30 min of hypercapnia (7% CO₂) in Wistar (blue dots) and WAR groups (red dots). Peak changes in baseline body temperature (ΔTb, ΔC, B) 30 after the beginning of hypercapnia (7% CO₂) in Wistar (blue bar, n = 9) and WAR groups (red bar, n = 6). The arrow indicates the moment of the establishment of hypercapnia. Data shown are expressed as mean ± SEM. p<0.05.</p