Dentate granule cells, at the gate of the hippocampus, use coincidence detection of synaptic inputs to code afferent information under a sparse firing regime. In both human patients and animal models of temporal lobe epilepsy, mossy fibers sprout to form an aberrant glutamatergic network between dentate granule cells. These new synapses operate via long-lasting kainate receptor-mediated events, which are not present in the naive condition. Here, we report that in chronic epileptic rat, aberrant kainate receptors in interplay with the persistent sodium current dramatically expand the temporal window for synaptic integration. This introduces a multiplicative gain change in the input-output operation of dentate granule cells. As a result, their sparse firing is switched to an abnormal sustained and rhythmic mode. We conclude that synaptic kainate receptors dramatically alter the fundamental coding properties of dentate granule cells in temporal lobe epilepsy.

The ability to flexibly navigate an environment relies on a hippocampal-dependent cognitive map. External space can be internally mapped at different spatial resolutions. However, whether hippocampal spatial coding resolution can rapidly adapt to local features of an environment remains unclear. To explore this possibility, we recorded the firing of hippocampal neurons in mice navigating virtual reality environments, embedding or not local visual cues (virtual 3D objects) in specific locations. Virtual objects enhanced spatial coding resolution in their vicinity with a higher proportion of place cells, smaller place fields, increased spatial selectivity and stability. This effect was highly dynamic upon objects manipulations. Objects also improved temporal coding resolution through improved theta phase precession and theta timescale spike coordination. We propose that the fast adaptation of hippocampal spatial coding resolution to local features of an environment could be relevant for large-scale navigation.

1Animals can flexibly navigate in their environment. This ability is thought to rely on an 2 internal cognitive map. An open question concerns the influence of local sensory cues on the 3 cognitive map and notably their putative contribution to setting its spatial resolution. Here 4 we compared the firing of hippocampal principal cells in mice navigating virtual reality 5 environments in the presence or absence of local visual cues (virtual 3D objects). Objects 6 improved the spatial representation both quantitatively (higher proportion of place cells) 7 and qualitatively (smaller place fields with increased spatial selectivity and stability). This 8 gain in spatial coding resolution was more pronounced near the objects and could be rapidly 9 tuned by their manipulations. In addition, place cells displayed improved theta phase 10 precession in the presence of objects. Thus the hippocampal mapping system can 11 dynamically adjust its spatial coding resolution to local sensory cues available in the 12 environment. 13All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

We propose that this aberrant activity-dependent intrinsic plasticity, which lastingly impairs the information processing of cortical inputs in dentate gyrus, may participate in hippocampal-related cognitive deficits, such as those reported in patients with epilepsy.

In theory, a safe approach to an intersection implies that drivers can simultaneously manage two scenarios: they either choose to cross or to give way to an oncoming vehicle. In this article we formalize the critical time for safe crossing (CTcross) and the critical time for safe stopping (CTstop) to represent crossing and stopping possibilities, respectively. We describe these critical times in terms of affordances and empirically test their respective contribution to the driver's decision-making process. Using a driving simulator, three groups of participants drove cars with identical acceleration capabilities and different braking capabilities. They were asked to try to cross an intersection where there was an oncoming vehicle, if they deemed the maneuver to be safe. If not, they could decide to stop or, as a last resort, make an emergency exit. The intersections were identical among groups. Results showed that although the crossing possibilities (CTcross) were the same for all groups, there were between-group differences in crossing frequency. This suggests that stopping possibilities (CTstop) play a role in the driver's decision-making process, in addition to the crossing possibilities. These results can be accounted for by a behavioral model of decision making, and provide support for the hypothesis of choice between affordances.

Visual Abstract

1The dentate gyrus (DG) plays a crucial role in learning, memory and spatial navigation. Only a 2 small fraction of mature dentate granule cells (mDGCs) is active during behavior, while the 3 large majority remains silent. To date, the properties of this active subset of neurons remain 4 61 5 throughout the experiment (see Materials and Methods), received a water reward at the end of 62 the track after successfully traversing the full track length. After receiving a reward at the first 63 reward zone, the mice then turned around for running in the opposite direction to receive the 64 next reward at the end of the track. In the first sessions (up to 8), the mice moved slowly and 65 erratically along the track as they learned the task. By 8-10 sessions, the mice moved 66 consistently back and forth along the track, and they received rewards at increasing rates over 67 time (1.14 ± 0.05 reward/min, n = 8 mice), they ran reliably back and forth along the track, and 68 they slowed down before reaching the track end consistent with learning of the task (Figure 69 1C). 70To analyse the fraction of DGCs activated in the different behavioral contexts (see above), we 71 used a strain of transgenic mice in which the synthesis of fosGFP fusion protein is controlled 72 by the promoter of the activity-dependent immediate early gene (IEG) c-fos (see Materials and 73 Methods). These mice enabled an ex vivo characterization of activated cells with a recent history 74 of elevated activity in vivo (Barth et al., 2004; Yassin et al., 2010) . In VR training conditions, 75 examination of cells expressing fosGFP was performed ex vivo in hippocampal slices obtained 76 shortly after the last training session (about 18-20 sessions, see Materials and Methods).77Quantification of cells expressing fosGFP was performed in the dorsal hippocampus, which is 78 known to play a crucial role in spatial memory (Moser et al., 1993). When mice were 79 maintained in their home cage, a discreet fraction of DGCs (Prox1-positive, Figure 2C) was 80 activated, since they expressed fosGFP (fosGFP + cells) (1.06 ± 0.1% of DGCs, n = 25 slices, n 81 = 6 mice) (see Figure 1D,E, Materials and Methods) . In line with previous observations (Liu 82 et al., 2012; Kirschen et al., 2017; Shevtsova et al., 2017; Stefanelli et al., 2016), we observed 83 a significant higher fraction of fosGFP + cells in the dorsal hippocampus in mice trained in VR 84(1.92 ± 0.16% of DGCs, n = 19 slices, n = 5 mice, p< 0.0001) ( Figure 1D, E). 85 6 We then explored the distribution of fosGFP + cells across the DG in dorsal hippocampus in the 86 different experimental conditions. To address this question, we plotted the localization of 87 fosGFP + cells in DG and investigated their lateral and radial distributions. DG cell layer extends 88 laterally from the upper (suprapyramidal) blade to the lower (infrapyramidal) blade and from 89 the outer layer (near the molecular layer) to the inner layer (near the hilus) in a radial direction 90 (Altman and Bayer , 1990). In order to reliably...

The dentate granule cells (DGCs) play a crucial role in learning and memory. Many studies have described the role and physiological properties of these sparsely active neurons using different behavioral contexts. However, the morpho-functional features of DGCs recruited in mice maintained in their home cage (without training), considered as a baseline condition, have not yet been established. Using fosGFP transgenic mice, we observed ex vivo that DGCs recruited in animals maintained in the home cage condition are mature neurons that display a longer dendritic tree and lower excitability compared with non-activated cells. The higher GABAA receptor-mediated shunting inhibition contributes to the lower excitability of DGCs activated in the home environment by shifting the input resistance towards lower values. Remarkably, that shunting inhibition is neither observed in non-activated DGCs nor in DGCs activated during training in virtual reality. In short, our results suggest that strong shunting inhibition and reduced excitability could constitute a distinctive neural signature of mature DGCs recruited in the context of the home environment.