Kainate receptors modulate the microstructure of synchrony during dentate gyrus epileptiform activity.

Temporal Lobe Epilepsy (TLE) is the most common form of epilepsy in adults. In TLE, recurrent mossy fiber (rMF) sprouting from dentate gyrus granule cells (DGCs) forms an aberrant epileptogenic network between dentate granule cells (DGCs) that operates via ectopically expressed kainate receptors (KARs). It was previously shown that KARs expressed at the rMF-DGC synapses play a prominent role in epileptiform network events in TLE. However, it is not well understood how KARs influence neuronal network dynamics and contribute to the generation of epileptiform network activity in the dentate gyrus. To address this question, we monitored the activity of DGCs using single-cell resolution calcium imaging performed in a reliable in vitro model of TLE. Under our experimental conditions, the most prominent DGC activity patterns were interictal-like epileptiform network events, which were correlated with high levels of neuronal synchronization. The pharmacological blockade of KARs reduced the frequency as well as the number of neurons involved in these events, without altering their spatiotemporal dynamics. Analysis of the microstructure of synchrony showed that blockade of KARs diminished the fraction of neurons forming the main functional cluster. Therefore, we propose that KARs act as modulators in the epileptic network by facilitating the recruitment of neurons into coactive cell assemblies, thereby contributing to the occurrence of epileptiform network events.

Substantial outcome improvement using a refined pilocarpine mouse model of temporal lobe epilepsy.

Systemic pilocarpine treatment is one of the most reliable means of inducing temporal lobe epilepsy (TLE). However, the traditional pilocarpine injection protocol using mice was associated with a high death rate, possibly because of cardiorespiratory collapse following status epilepticus (SE). To prevent this, we developed a modified procedure of pilocarpine SE induction, which included a single injection of a moderate dose of caffeine during the induction phase. That new protocol was based on the use of young male mice as well as on a refined Racine's scale. Using that protocol, we report a substantially increased survival rate, thus enabling the generation of a large cohort of mice that exhibited cardinal histological (e.g., mossy fiber sprouting) and electrophysiological (e.g., chronic interictal events and ictal seizures) characteristics associated with TLE. In conclusion, our refined caffeine- and pilocarpine-based protocol substantially improves the outcome of the reliable pilocarpine mouse model of TLE.

Dentate Granule Cells Recruited in the Home Environment Display Distinctive Properties.

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.

Ethyl hexanoate transfer modeling in carrageenan matrices for determination of diffusion and partition properties.

Aroma compound properties in food matrices, such as volatility and diffusivity, have to be determined to understand the effect of composition and structure on aroma release and perception. This work illustrates the use of mass transfer modeling to identify diffusion and partition properties of ethyl hexanoate in water and in carrageenan matrices with various degrees of structure. The comparison of results obtained with a diffusive model to those obtained with a convective model highlights the importance of considering the appropriate transfer mechanism. Modeling of the preliminary experimental steps ensures correct estimation of the conditions for the main aroma release step. The obtained values of partition and diffusion coefficients are in agreement with those found in the literature (either experimentally determined or predicted by theoretical equations) and demonstrate that the structure level of carrageenan matrices has little influence on diffusion properties of ethyl hexanoate (less than 20%).